Med Chem [JOURNAL]
Sun
200 papers
Computational Screening, ADME Study, and Evaluation of Benzothiazole Derivatives as Potential Anticancer Agents.
Banwala S, Kush A, Aggarwal S … +2 more , Sharma S, Sindhu RK
Med Chem · 2026 Jan · PMID 41620923 · Publisher ↗
INTRODUCTION: Benzothiazole derivatives have garnered considerable interest in medicinal chemistry due to their diverse biological activities, including anticancer potential. The synthesis of 2-substituted benzothiazoles...
INTRODUCTION: Benzothiazole derivatives have garnered considerable interest in medicinal chemistry due to their diverse biological activities, including anticancer potential. The synthesis of 2-substituted benzothiazoles is traditionally achieved via two main approaches: (1) condensation of 2-aminothiophenols with aldehydes or carboxylic acid derivatives under highly acidic conditions, and (2) cyclization of thiobenzanilides. In this study, approximately 65 benzothiazole analogs were evaluated for anticancer potential using in silico tools and ADME profiling. MATERIALS AND METHODS: ADME properties were predicted using SwissADME, while molecular docking studies were performed using Molegro Virtual Docker 6.0. Gefitinib and Erlotinib were used as reference drugs for both pharmacokinetic and in silico comparisons. Biological activity predictions were conducted using the PASS online web server. RESULTS: Docking scores for the analogs ranged from -134.60 to -114.36, with several compounds outperforming standard drugs Gefitinib (-122.87) and Erlotinib (-119.22). Compounds 12, 17, 27, 43, and 49 exhibited five hydrogen bond interactions, whereas compound 45 showed a maximum of six, exceeding the interactions observed for the standard drugs. Most compounds had molecular weights below 500 and favorable Log P values (e.g., compounds 4: 2.34, 5: 2.85, 7: 2.56, 10: 2.76, 17: 2.78, 19: 2.51, 26: 2.09, 30: 1.20, 40: 1.78, 45: 1.76, 56: 1.75), lower than the reference drugs (3.92, 3.20). Selected compounds also displayed improved topological polar surface area (TPSA) values (e.g., 5: 80.05 Ų, 11: 79.46 Ų, 13: 71.83 Ų, 15: 87.74 Ų, 23: 68.82 Ų, 32: 61.36 Ų, 36: 45.53 Ų, 52: 41.13 Ų) compared to standard drugs (68.74 Ų, 74.73 Ų). Targeting EGFR using PASS predictions, compounds 32, 33, 35, 39, 46, and 48 exhibited activities similar to Gefitinib and Erlotinib. DISCUSSION: Docking and ADME analyses indicated that several benzothiazole analogs outperformed standard drugs in binding affinity and pharmacokinetic profiles. EGFR, a transmembrane receptor tyrosine kinase, plays a central role in cell proliferation, survival, angiogenesis, and migration. Most compounds demonstrated good gastrointestinal absorption, suggesting favorable oral bioavailability according to Lipinski, Ghose, Veber, Egan, and Muegge rules. PASS predictions indicated potential anticancer activities, including inhibition of transcription factor STAT3, DNAdirected RNA polymerase, Mcl-1, proto-oncogene tyrosine-protein kinase Fgr, and EGFR, with potential antineoplastic effects across multiple cancer types, including solid tumors, lung, gastric, lymphoma, sarcoma, breast, and pancreatic cancers. CONCLUSION: Compounds 12, 17, 27, 43, 45, and 49 demonstrated strong binding affinities and superior pharmacokinetic profiles compared to Gefitinib and Erlotinib. Overall, benzothiazole derivatives represent a promising scaffold for the design of EGFR inhibitors, potentially contributing to targeted anticancer therapy.
Carboxylic Acids as Activators of NRF2: Antioxidant and Anti-inflammatory Effects.
Egbujor MC
Med Chem · 2025 · PMID 41607070 · Publisher ↗
The complex interaction between carboxylic acids and molecular signaling pathways, particularly the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, is of growing interest in medicinal chemistry due to its pot...
The complex interaction between carboxylic acids and molecular signaling pathways, particularly the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, is of growing interest in medicinal chemistry due to its potential therapeutic benefits. Carboxylic acids, which are widely distributed in nature, are versatile regulators of cellular responses due to their ability to interact with multiple signaling pathways, especially those involved in combating oxidative stress and inflammation. Several carboxylic acids exhibit significant antioxidant and anti-inflammatory activities. They have been identified as potential activators of the NRF2 transcription factor, a key regulator of endogenous antioxidants that maintains cellular redox homeostasis and modulates the production of several antioxidant proteins and detoxifying enzymes. The potential effects of carboxylic acid-NRF2 crosstalk are exhibited in a variety of physiological processes, such as attenuation of oxidative stress and inflammation, detoxification of xenobiotics, and modulation of the immune system. The molecular docking of some carboxylic acids with. NRF2 protein showed that their binding affinities were comparable to dimethyl fumarate, a reference drug. The current review explores the evolving landscape of carboxylic acid-NRF2 interactions and their mechanisms of action, highlighting the possible impact of their antioxidant and anti-inflammatory effects on inflammation and oxidative stress-mediated diseases. The natural and synthetic sources of NRF2-activating carboxylic acids and the role of their chemical and physical properties in influencing NRF2-inducing activities were discussed. Their potential challenges as future drugs and clinical trial prospects were also highlighted. Carboxylic acid-NRF2 interactions offer potential for developing therapies that will attenuate oxidative stress and inflammation.
Benzimidazole and Benzimidazole Derivatives as Anticancer Scaffolds: A Review of Synthetic Approaches.
Ray PK, Verma S, Alam MS … +2 more , Mishra SK, Chauhan V
Med Chem · 2026 Jan · PMID 41603172 · Publisher ↗
INTRODUCTION: The objective of exploiting benzimidazole, a chemical compound with the molecular formula C7H6N2, varies depending on its application. In this review, articles published between 2001 and 2025 were analyzed....
INTRODUCTION: The objective of exploiting benzimidazole, a chemical compound with the molecular formula C7H6N2, varies depending on its application. In this review, articles published between 2001 and 2025 were analyzed. Its adaptability and multiple chemical properties make it valuable in fields such as pharmaceuticals, materials science, and chemical research. The structural characteristics of benzimidazole allow for a wide range of modifications and applications. METHODS: The benzimidazole derivatives were synthesized and analyzed. An extensive literature search was conducted using databases such as Google Scholar, PubMed, ScienceDirect, SpringerLink, Wiley Online Library, RSC Publishing, and Eureka Select. Key synthetic methods, including Philip's reaction, oxidative/reductive cyclization, multicomponent reactions, and microwave-assisted synthesis, were illustrated using ChemDraw Ultra. RESULTS: This review outlines synthetic strategies for developing potent benzimidazole-based anticancer agents, highlighting their therapeutic potential through a summary of in vitro efficacy in inducing apoptosis and cell cycle arrest across various cancer cell lines. DISCUSSION: Benzimidazole derivatives exhibit strong in vitro anticancer activity through apoptosis and cell cycle arrest, yet face challenges such as low bioavailability and limited clinical translation. The review highlights gaps in resistance mechanisms and delivery strategies, urging the use of in vivo studies, SAR-based optimization, and clinical advancement to realize their therapeutic potential. CONCLUSION: The study highlights the chemical versatility of benzimidazole scaffolds and their structure-activity relationships in the design of anticancer drugs. Key findings emphasize efficient synthetic methodologies and functional modifications that enhance bioactivity. These insights contribute to the rational development of novel, potent anticancer agents, reinforcing the value of benzimidazoles in medicinal chemistry.
Identification of Novel and Selective Cyclooxygenase 2 (COX-2) Inhibitors: Comprehensive Investigations.
Xavier A, Komali MV, Sawant A … +4 more , Botelho S, Chokey S, Dibia KT, Pissurlenkar RRS
Med Chem · 2026 Jan · PMID 41588985 · Publisher ↗
INTRODUCTION: Cyclooxygenase-2 (COX-2) is a key enzyme in the inflammatory cascade and is implicated in chronic conditions, including arthritis, cancer, and cardiovascular diseases. Selective inhibition of COX-2, while s...
INTRODUCTION: Cyclooxygenase-2 (COX-2) is a key enzyme in the inflammatory cascade and is implicated in chronic conditions, including arthritis, cancer, and cardiovascular diseases. Selective inhibition of COX-2, while sparing COX-1, is crucial to minimize gastrointestinal and renal side effects associated with non-selective NSAIDs. Computational drug discovery offers a strategic advantage for efficiently identifying novel, selective COX-2 inhibitors. METHODS: Comprehensive in-silico studies were performed, which included ligand and structurebased screening, ML-based QSAR model, ADME/toxicity profiling, and molecular dynamics simulation. Five potent COX-2 inhibitors were used as query compounds to identify a dataset of 9213 similar molecules using the SwissSimilarity Server, which employed fingerprint-based screening of the ZINC database. Subsequently, these molecules were docked into the active sites of the COX-1 and COX-2 targets using AutoDock Vina to discover selective COX-2 inhibitors. RESULTS: A pool of 236 compounds was selected based on docking scores (≤ -8.0 kcal/mol for COX-2 and ≥ -6.0 kcal/mol for COX-1), indicating potential selectivity. ADME/toxicity filtering narrowed the pool to 23 candidates. QSAR predictions identified 13 biologically active molecules, which were further evaluated for toxicity. Molecular dynamics simulations confirmed ten compounds with stable binding and favorable interaction profiles. DISCUSSION: The integrated computational workflow enabled the identification of ten highly selective COX-2 inhibitors with promising pharmacokinetic and safety profiles. These candidates demonstrated strong potential for experimental validation and development into anti-inflammatory therapeutics. CONCLUSION: The in-silico studies offer valuable insights into discovering selective COX-2 inhibitors for potential therapeutic and pharmacological applications. The findings provide a strong foundation for future experimental validation and the development of anti-inflammatory medicine.
Identification of Novel Inhibitors Targeting Dengue Virus Serotype 3 RNA-Dependent RNA Polymerase.
Mallya S, Pissurlenkar RRS
Med Chem · 2026 Jan · PMID 41588893 · Publisher ↗
INTRODUCTION: Dengue infection, caused by four serotypes of the dengue virus (DENV), poses a significant global health threat, with millions of cases reported annually. RNAdependent RNA polymerase (RdRp) is an essential...
INTRODUCTION: Dengue infection, caused by four serotypes of the dengue virus (DENV), poses a significant global health threat, with millions of cases reported annually. RNAdependent RNA polymerase (RdRp) is an essential viral enzyme involved in the replication cycle and is a promising target for antiviral drug development. In the present study, computational methods were employed to identify novel compounds with potential inhibitory activity against DENV serotype 3 RdRp. METHODS: Molecular docking-based virtual screening approaches were used to screen a diverse library of small molecules against the three-dimensional structure of DENV-3 RdRp. Furthermore, pharmacokinetic and toxicity predictions were utilized to prioritize compounds with favorable drug-like properties. Subsequently, molecular dynamics simulation studies were performed to assess the stability and binding affinity of the predicted inhibitors. RESULTS: The computational studies yielded three promising DENV serotype 3 RNA-dependent RNA polymerase inhibitors, with docking scores ranging from -8.89 to -8.19 kcal/mol. MD simulations over 100 ns demonstrated stable protein-ligand complexes, with backbone RMSDs varying from 0.77 to 1.87 Å. DISCUSSIONS: Comprehensive interaction analysis revealed that Z248 and Z982 engaged key catalytic residues Arg729 and Arg737 within the palm domain, while Z389 exhibited hydrophobic stabilization through interaction with Trp795. These residues are critical for enzymatic activity, and their engagement highlights the mechanistic relevance of the identified compounds. The dynamic stability of the RdRp-ligand complexes was further validated through 100 ns molecular dynamics simulations, with both protein backbone and ligand RMSDs remaining within acceptable limits. CONCLUSIONS: The identified inhibitors, obtained from exhaustive computational studies, represent promising candidates for further experimental validation and optimization as potential antiviral agents for the treatment of DENV-3 infections.
Harnessing Purines: Anticancer Activity and Target-Specific Approaches.
Arora G, Kalra S, Kaur R … +1 more , Sharma R
Med Chem · 2026 Jan · PMID 41588892 · Publisher ↗
INTRODUCTION: In the discovery of anticancer drugs, Purine analogues demonstrated crucial attention due to their structural similarity to natural purines, which are essential for DNA and RNA synthesis. Cytotoxic effects...
INTRODUCTION: In the discovery of anticancer drugs, Purine analogues demonstrated crucial attention due to their structural similarity to natural purines, which are essential for DNA and RNA synthesis. Cytotoxic effects are exerted by these compounds by interfering with nucleic acid metabolism, enzymatic activity and signal transduction, which is necessary for cancer cell proliferation. METHODS: This study was carried out to investigate the potential anticancer effects of purine-based hybrid compounds by evaluating their impact on cell cycle regulation, proinflammatory cytokine inhibition, and induction of apoptotic gene expression in cancer cells. The studies involve peerreviewed articles on purine analogues used in cancer therapy, which focus on molecular targets, preclinical or clinical efficacy data and structure-activity relationships (SAR). RESULTS: Classic purine analogues such as 6-mercaptopurine, thioguanine, and cladribine have proven effective against hematologic cancers. Recent innovations have broadened their use to solid tumours by targeting kinases (e.g., CDKs, PI3K), epigenetic regulators (e.g., DNMTs), and immune checkpoints. Improved molecular modelling and SAR studies have enhanced drug specificity and pharmacokinetics. Additionally, combining purine analogues with other chemotherapeutics or targeted agents has shown synergistic effects and potential for overcoming resistance. DISCUSSION: The current outlook of the purine-based anticancer agents is aimed at this review by concentrating on their mechanisms of action, the development of target-specific strategies and therapeutic targets for the enhancement of anticancer efficacy and decreasing target toxicity. CONCLUSION: For the anti-cancer drugs, Purine-based compounds remain a versatile and evolving class. Their targeted design offers promising avenues for personalized cancer therapy, warranting further clinical exploration.
Diaryl Ether Derivatives as Dual Inhibitors of Selective COX-2 and EGFR: Synthesis, , and Analysis.
Saha V, Hoque A, Ali A … +4 more , Sarkar S, Pradhan PK, Pradhan SD, Biswas G
Med Chem · 2026 Jan · PMID 41582578 · Publisher ↗
INTRODUCTION: The rising prevalence of cancers with chronic inflammation is a leading global health concern. Modern anticancer treatments require dual inhibitors of cyclooxygenase- 2 (COX-2) and Epidermal Growth Factor R...
INTRODUCTION: The rising prevalence of cancers with chronic inflammation is a leading global health concern. Modern anticancer treatments require dual inhibitors of cyclooxygenase- 2 (COX-2) and Epidermal Growth Factor Receptor (EGFR) with minimal adverse effects. METHODS: The emergence of diaryl ether derivatives has encouraged the development of new therapeutic strategies for inflammation-linked conditions. A series of nine diaryl ether derivatives was designed, and in silico studies were performed to predict their interactions with COX- 1, COX-2, and EGFR proteins. Drug likeness and toxicity characteristics were investigated using Swiss ADME, ADMET Lab 2.0, and ProTox-3.0 tools. Furthermore, to observe the selective COX-2 inhibitory nature, a protein (bovine serum albumin (BSA)) denaturation study of the five best compounds with high binding affinities was conducted. RESULTS: Nine diaryl ether derivatives were synthesized and characterized using 1H-NMR, 13C NMR, LC-MS, and FT-IR spectroscopy. Based on the docking score and pharmacokinetics, compound 12a showed a significant IC50 value of 39.24 μg/mL in the BSA denaturation assay. To screen the kinetic behavior of five selected compounds with high binding affinities (11a, 12a, 12b, 12c, and 13a) with COX-2, Molecular Dynamics (MD) simulations were performed for 100 ns. MD simulations and binding free energy calculations were performed to observe the stability of the best-docked EGFR-12a complex with a docking score of -9.5 kcal/mol. CONCLUSION: This study focused on the synthesis and biological analysis with theoretical explanations. Overall, diaryl ether derivatives are promising precursors for anti-inflammatory and anticancer drugs in the biomedical field.
Synthesis, Docking, and Biological Studies of Pyrazine Derivatives as Antimycobacterial Agents.
Gangarapu NR, Ranganatham A, Reddy EK … +4 more , Kumar CK, Yellappa S, Chandrasekhar KB, Manickan E
Med Chem · 2025 · PMID 41498239 · Publisher ↗
INTRODUCTION: A series of novel 2-((3,5-diphenylpyrazin-2-yl)amino)-1-(piperidin-1- yl/pyrrolidin-1-yl)ethanone derivatives (5a-5l) were synthesized and evaluated for their tuberculosis activity using the standard strain...
INTRODUCTION: A series of novel 2-((3,5-diphenylpyrazin-2-yl)amino)-1-(piperidin-1- yl/pyrrolidin-1-yl)ethanone derivatives (5a-5l) were synthesized and evaluated for their tuberculosis activity using the standard strain H37Rv and two other clinically isolated multidrug-resistant strains with different resistances. METHODS: All compounds 5a-5l showed promising results in tuberculosis activity. Among them, 5g and 5i demonstrated remarkable activity at 5 μg/mL against H37Rv and three other MDR strains. The compounds 5c, 5d, and 5f were sensitive, showing inhibition between 15-25 μg/mL against M. tuberculosis growth. In-silico docking studies were conducted for 5a-5l using the 2FUM protein of M. tuberculosis. RESULTS: These studies revealed that compounds 5g and 5i exhibited strong interactions with the MTB protein, with binding energies of -9.85 kcal/mol and -10.74 kcal/mol, respectively, and inhibitory concentrations of 0.38 μM and 0.77 μM. CONCLUSION: Moreover, these motifs also displayed good binding energy coupled with favorable minimum inhibitory concentrations (MIC).
Synthesis, Pharmacological Activities, Structure-activity Relationship of 1,3,4-Oxadiazole-Piperazine Conjugates: A Review.
Sharma U, Kumar R, Mazumder A … +3 more , Salahuddin, Tyagi PK, Singh S
Med Chem · 2025 · PMID 41498238 · Publisher ↗
The conjugation of heterocyclic compounds often aims to leverage the beneficial properties of multiple compounds, which ultimately motivate the researchers to develop novel medicines with better efficacy, affinity, modif...
The conjugation of heterocyclic compounds often aims to leverage the beneficial properties of multiple compounds, which ultimately motivate the researchers to develop novel medicines with better efficacy, affinity, modified selectivity, dual/various modes of action, reduced side effects, lower cost, or enhanced therapeutic profiles. Hybrid molecules or conjugates for synergistic effect are obtained by combining structural features of two differently active fragments. Due to 1,3,4-oxadiazole's alternating single and double bonds, each atom providing a porbital perpendicular to the molecule's plane is stabilized like a drug molecule. The conjugate of 1,3,4-oxadiazole with piperazine moiety exhibits a range of physiological effects such as lowering blood pressure, antimicrobial, antitubercular, antioxidant, anticancer, antiproliferative, etc. Numerous natural molecules with pharmacological importance have also been found to possess conjugation between piperazine and 1,3,4-oxadiazole. As there is a lack of studies that focused on the synthetic protocols, pharmacological potential, and structure-activity relationship of the conjugates of 1,3,4-oxadiazoles and piperazines, the presented article highlights specifically these dimensions which have been reported in the last 10 years (2014-2024) These details assist researchers in designing their studies, and it is hoped that researchers from various scientific fields will find the manuscript beneficial for their future work on the conjugates of 1,3,4-oxadiazoles and piperazine.
Targeting Breast Cancer: Novel Dihydropyrimidinones As Potent Eg5 Inhibitors.
Nikam D, Jain A, Vetale S … +2 more , Bhange A, Jadhav S
Med Chem · 2025 · PMID 41395721 · Publisher ↗
INTRODUCTION: Breast cancer remains a formidable health concern for women, necessitating the development of potent anticancer agents with improved safety profiles. Dihydropyrimidinones (DHPM), pyrazole, and benzofuran sc...
INTRODUCTION: Breast cancer remains a formidable health concern for women, necessitating the development of potent anticancer agents with improved safety profiles. Dihydropyrimidinones (DHPM), pyrazole, and benzofuran scaffolds have emerged as promising targets due to their diverse pharmacological profiles. In this study, we employed a scaffold hopping approach to design a novel DHPM-Pyrazole-Benzofuran core. A series of compounds (3a-3j) were synthesized using the Biginelli protocol, and their characterization was performed using various techniques such as FTIR, H NMR, and Mass spectroscopy. METHODS: Molecular docking studies against kinesin spindle protein Eg5 (1Q0B) performed to find superior binding interactions compared to the prototype Eg5 inhibitor Monastrol. Anti breast cancer potential of these compounds was screened against the breast adrenocarcinoma MCF-7 cell line using an SRB assay. RESULTS: Compound 3j showed good growth inhibitory activity (GI=24.08 μM) compared to Monastrol (GI=32 μM) employed as a positive control. Moreover, Compound 3j exhibited strong interactions with amino acids GLU-116 and ARG-119 with Eg5 protein 1Q0B. CONCLUSION: Compound 3j fits well at the allosteric site of Eg5 protein 1QOB. Compound 3j emerged as the most cytotoxic, displaying significant and impressive growth inhibitory activity (GI=24.08 μM).
Design, Synthesis, Anti-Proliferative Effects, and Mechanistic Details of Fluorine-Containing Biguanide Derivatives with Various Carbon Rings.
Xie Y, Zhang Q, Xiao D … +4 more , Deng M, Liu Y, Duan H, Yang X
Med Chem · 2025 · PMID 41395720 · Publisher ↗
INTRODUCTION/OBJECTIVE: Biguanide derivatives are small molecules with promising antitumor activity. However, the effect of different carbon rings at the end of one guanide group of these compounds on anti-proliferation...
INTRODUCTION/OBJECTIVE: Biguanide derivatives are small molecules with promising antitumor activity. However, the effect of different carbon rings at the end of one guanide group of these compounds on anti-proliferation activity is unknown. Therefore, we synthesized novel fluorine- containing biguanide compounds with various carbon rings, evaluated their anticancer activities, and explored their anti-proliferative mechanisms. METHODS: Guanidine derivatives containing trifluoromethoxy or 3,4-difluorophenyl with nine different carbon rings were synthesized using established chemical methods. The phenyl side chain was fixed to trifluoromethoxy or 3,4-difluorophenyl with changes in the number of cyclic aminocyclic carbons. The effects of these derivatives were evaluated using MTT and clonogenic assays, while the underlying mechanisms were investigated by analyzing protein expression levels via western blotting. RESULTS: This study analyzed the effects of new biguanide derivatives on cell growth in three different cell lines: HepG2, Ovcar3, and T24. The results showed that T24 cells were the most sensitive cell line to these biguanides. All biguanide derivatives significantly inhibited the growth of T24 cells, while compound 4b exhibited the strongest inhibition in all three cell lines by MTT assay. The inhibitory effects of 4b were further confirmed using colony formation experiments. Western blotting results indicated that the representative biguanide derivative, 4b, inhibited the EGFR signaling pathway, thereby inhibiting tumor growth. CONCLUSION: 1a-5a and 1b-4b, the cyclooctyl-containing 3,4-difluorophenyl biguanide analogs, have demonstrated significant potential in developing novel anticancer drugs. The 3,4- difluorophenyl biguanide containing cyclooctyl showed the best antitumor activity among the nine derivatives. This finding offers a novel perspective in developing anticancer drugs and a further improvement in biguanide activity in the future.
Pyridazinone: Current Progress in Synthesis of its Derivatives and Biological Activity.
Pathak S, Sharma V, Agrawal N … +1 more , Sharma S
Med Chem · 2025 · PMID 41395719 · Publisher ↗
Pyridazinone, a six-membered heterocyclic molecule, has emerged as an important pharmacophore in drug discovery due to its diverse range of biological actions. This adaptable scaffold has shown tremendous promise in the...
Pyridazinone, a six-membered heterocyclic molecule, has emerged as an important pharmacophore in drug discovery due to its diverse range of biological actions. This adaptable scaffold has shown tremendous promise in the development of therapeutic medicines for a variety of pharmacological conditions, including anti-inflammatory, anti-cancer, anti-microbial, cardiovascular, and central nervous system illnesses. Pyridazinone derivatives are useful in medicinal chemistry due to their propensity to interact with a wide range of biological targets. This review offers a comprehensive overview of Pyridazinone-based compounds, focusing on their chemical structure, mechanism of action, structure-activity relationship (SAR), and therapeutic uses. Current trends in Pyridazinone research and its potential as a lead chemical for new medication development are also reviewed. Pyridazinone broad range of activity and adaptability highlight its importance in developing pharmacotherapy.
Unveiling Indazole: Novel Synthetic Pathways and Biological Potentials.
Pathak S, Goswami A, Sharma K
Med Chem · 2025 · PMID 41395718 · Publisher ↗
Indazole, a heterocyclic molecule, has emerged as a useful scaffold in synthetic and medicinal chemistry due to its broad biological activity and ease of synthesis. This article thoroughly analyzes unique synthetic metho...
Indazole, a heterocyclic molecule, has emerged as a useful scaffold in synthetic and medicinal chemistry due to its broad biological activity and ease of synthesis. This article thoroughly analyzes unique synthetic methods used to diversify indazole derivatives, such as metal-catalyzed reactions, ecologically friendly approaches, and novel multicomponent reactions. These advances have increased the efficiency and selectivity of indazole synthesis and its structural variety, paving the path for new biological applications. Furthermore, indazole-based compounds have demonstrated promising biological activities, particularly as anticancer, antibacterial, and anti-inflammatory medicines. This review summarizes the present state of indazole research, focusing on synthetic techniques and biological features that make indazole an attractive target for future drug discovery.
Imidazole-Based Metal Complex Derivatives: A Comprehensive Overview of Synthesis and Biological Applications.
Hiremath AF, Kumar MRP, Rajagopal K … +4 more , Barua R, Rab SO, Alshehri MA, Bin Emran T
Med Chem · 2025 · PMID 41395717 · Publisher ↗
The imidazole scaffold is a cornerstone in medicinal chemistry, widely recognized for its extensive range of biological activities and ability to form stable metal complexes. This review article provides a detailed overv...
The imidazole scaffold is a cornerstone in medicinal chemistry, widely recognized for its extensive range of biological activities and ability to form stable metal complexes. This review article provides a detailed overview of recent advancements in synthesizing, characterization, and biological evaluation of metal-complexed imidazole derivatives. We explored various synthetic strategies to create diverse metal-based imidazole complexes, emphasizing innovations that enhance efficiency and yield. Furthermore, we delve into the biological profiling of imidazole derivatives, summarizing key findings from studies investigating their antimicrobial, antifungal, anticancer, and other therapeutic properties. Special attention is given to metal coordination's role in modulating these compounds' biological activity. The review discusses the synthesis of imidazolemetal complexes, illustrating how metal ions such as copper, zinc, and iron enhance the pharmacological profiles of imidazole derivatives. Thus, the data from numerous studies was collated and analyzed to comprehensively understand the current landscape and future prospects in imidazole chemistry associated with metals. It is a valuable resource for researchers, guiding future investigations and fostering the development of novel metal-based imidazole therapeutics.
A Review of the Medicinal Importance and Perspectives of the 2-isoxazoline Scaffold.
Pathak S, Singh P, Jadon G
Med Chem · 2025 · PMID 41395716 · Publisher ↗
The 2-isoxazoline scaffold has emerged as a key structure in medicinal chemistry, with great therapeutic potential for a wide range of biological targets. This review investigates the medicinal value of the 2-isoxazoline...
The 2-isoxazoline scaffold has emerged as a key structure in medicinal chemistry, with great therapeutic potential for a wide range of biological targets. This review investigates the medicinal value of the 2-isoxazoline scaffold, emphasizing its adaptability and usefulness in the development of new medications. Isoxazoline has a wide range of biological actions, including antibacterial, anti-inflammatory, anticancer, and anti-parasitic effects, which are due to their distinct structural features and capacity to interact with a variety of biological processes. The synthesis, functionalization, and pharmacological uses of isoxazoline derivatives are rigorously studied, yielding information about their modes of action and therapeutic value. This review emphasizes the promise of isoxazoline-based molecules in tackling current medical difficulties and lays the way for future research in this vibrant field of medicinal chemistry.
Examination of Triazolinedione-Derived Dihydropyrrole Hybrid Compounds: ER Stress-Related Apoptosis in Breast Cancer Cells, Molecular Docking, and ADMET Analysis.
Mesci S, Ayar A, Yazgan B … +2 more , Gul M, Yıldırım T
Med Chem · 2025 · PMID 41368780 · Publisher ↗
BACKGROUND: In many types of cancer, uncontrolled growth and proliferation of cells occur due to abnormalities in their genes, mutations of pro-apoptotic proteins, or upregulation of anti-apoptotic proteins. Triazolinedi...
BACKGROUND: In many types of cancer, uncontrolled growth and proliferation of cells occur due to abnormalities in their genes, mutations of pro-apoptotic proteins, or upregulation of anti-apoptotic proteins. Triazolinedione and pyrrole derivatives are compounds with anti-microbial, anti-fungal, anti-inflammatory, and anti-cancer activities. Pyrrole and its derivatives are critical heterocycle compounds that are significant in anticancer studies and highly preferred in research. OBJECTIVE: This study aimed to investigate the effects of dihydropyrrole derivatives substituted with triazolinedione on the MCF-7 (breast cancer) cell line's apoptosis, ER stress, and heat shock genes. METHODS: The mRNA levels of apoptosis, ER stress, and heat shock proteins were assessed by qRT-PCR method in the MCF-7 cell line. The investigation of ADMET features, crucial pharmacokinetic indices for the potential candidacy of compounds as drugs, has been meticulously designed. -induced molecular docking studies were conducted to further explore the interaction and elucidate the orientation of hybrid compounds within the active sites of BCL-2, PARP, HSP70, HSP90, and GRP78. RESULTS: It was determined that the compounds caused cell death by modulating apoptotic (compound IV), ER stress, and heat shock proteins (compounds XI and XVI) through up- and downregulation. Our findings have pointed to the effects of triazolinedione-substituted dihydropyrrole derivatives, exhibiting antitumor activity on apoptosis, ER stress, and heat shock genes in the MCF- 7 cell line. CONCLUSION: The compounds investigated in this study have been found to be promising for anticancer research.
A Preclinical Study on 4-Methyl-N-((4-(trifluoromethoxy)phenyl) carbamoyl)-benzenesulfonamide as a Potent Chemotherapeutic Agent against Liver and Pancreatic Carcinogenesis in Rats: Immunohistochemical and Histopathological Studies.
Sroor FM, Younis EA, Aly HF
Med Chem · 2025 · PMID 41368779 · Publisher ↗
BACKGROUND: Alternative and complementary applications of newly synthesized chemicals have enhanced the prospect of finding curative treatments for hepatocarcinogenesis and pancreatic cancer. METHODS: The current study i...
BACKGROUND: Alternative and complementary applications of newly synthesized chemicals have enhanced the prospect of finding curative treatments for hepatocarcinogenesis and pancreatic cancer. METHODS: The current study investigated the curative effect of the newly synthesized drug 4- methyl-N-((4-(trifluoromethoxy) phenyl) carbamoyl) benzenesulfonamide (3) against diethyl nitrosamine (DEN) (50 mg/kg) and carbon tetrachloride (CCl) (2 mg/kg)-induced hepatocellular carcinoma (HCC) and pancreatic cancer in male rats using doxorubicin as a reference drug. RESULTS: The findings demonstrated that the DEN/CCl treatment produced oxidative stress, as evidenced by an increase in MDA and a reduction in GSH levels. A temporary decline in antioxidant and total antioxidant capacity (TAC) was detected. An increase in the levels of TNF-α and other inflammatory markers, interleukin-6 (IL-6) and B-cell lymphoma 2 (Bcl-2), was found. Our findings showed that the liver and pancreas had significantly higher levels of hepatocellular carcinoma biomarkers, namely α-fetoprotein and α-L-Fucosidase (α-FU). Changes in the biomarkers of hepatic function were also seen, with elevated levels of γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and transaminases (AST, ALT). Our findings were supported by immunohistochemical and pathological examinations, which revealed considerable improvement in liver and pancreatic tissues after treatment with medication 3 when compared to normal healthy rats. CONCLUSION: The new synthetic medication 3 could be an effective chemotherapeutic method for treating DEN and CCl-induced HCC and pancreatic cancer.
Design and Development of [1,2,4]Triazolo[4,3-b][1,2,4]triazines as Potential Anticancer Agents with Genotoxicity and Apoptotic Activity.
Khatir ZZ, Valipour M, Rahmani K … +4 more , Aghajanshakeri S, Shokrzadeh M, Irannejad H, Ghasemian M
Med Chem · 2025 · PMID 41368778 · Publisher ↗
AIMS: In this current study, a new series of triazolo-triazine derivatives were designed and synthesized as potential anticancer agents. METHODS: The antiproliferative activity of the new compounds was evaluated against...
AIMS: In this current study, a new series of triazolo-triazine derivatives were designed and synthesized as potential anticancer agents. METHODS: The antiproliferative activity of the new compounds was evaluated against four different cancerous cell lines (MDA-MB-231, HCT-116, A549, and HT-29) using an MTT assay. To evaluate the mechanism of action, the ability of the best compound in apoptosis induction and DNA damage was evaluated using the flow cytometry technique and comet assays. Furthermore, molecular docking simulation was used to investigate their interactions with the two targets, VEGFR2 and c-Met kinases. RESULTS: Results showed that 6-(4-bromophenyl)-3-((4-methoxybenzyl)thio)-[1,2,4]triazolo[4,3- b][1,2,4]triazine (8c) demonstrated the best anti-proliferative activity against the human colorectal carcinoma cells HCT-116 with an IC value of 38.7 ± 1.7 μM. evaluations showed that the triazolo-triazine scaffold, along with the methoxy substitution of compound 8c, was involved in creating effective H-bond interactions in the active site of both targets. CONCLUSION: Our results showed that compound 8c significantly increased cell death through apoptosis induction and caused a significant increase in genotoxicity. Furthermore, it was found that the tested compound 8c, with a selectivity index of 1.74, possessed selective antiproliferative activity towards the colorectal cancer cell line HCT-116 compared to the normal fibroblast cell line. These findings could be useful in the development of novel VEGFR2/c-Met dual-targeted inhibitors in the future.
Mapping the Landscape of Global Anticancer Organometallics Research: A Systematic Review.
Ur Rehman T, Abdulaziz Al Naam Y, Zahid M … +1 more , Algethami JS
Med Chem · 2025 · PMID 41368777 · Publisher ↗
AIM: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compoun...
AIM: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. METHODS: The study data related to anticancer organometallics were searched from Scopus between 1985 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. RESULTS: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. CONCLUSION: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.
Heterocyclic Compounds as Bcr-Abl Tyrosine Kinase Inhibitors Against Chronic Myeloid Leukemia.
Gado S, Hassan MA, Kisla MM … +1 more , Ates-Alagoz Z
Med Chem · 2025 · PMID 41368776 · Publisher ↗
Despite significant progress in oncology therapeutics, cancer remains a leading cause of mortality worldwide. Chronic myeloid leukemia, which accounts for 15% of all adult leukemia cases, is characterized by chromosomal...
Despite significant progress in oncology therapeutics, cancer remains a leading cause of mortality worldwide. Chronic myeloid leukemia, which accounts for 15% of all adult leukemia cases, is characterized by chromosomal abnormalities involving the fusion of the Bcr and Abl genes to form the Bcr-Abl oncogene. Current drug treatment of the disease involves the use of Bcr-Abl tyrosine kinase inhibitors belonging to the first, second, and third generations. However, the toxicity and resistance associated with the use of imatinib, a first-generation Bcr-Abl inhibitor, in cases where the T315I mutation exists, necessitates the need for new tyrosine kinase inhibitors. This review focuses on recent synthetic compounds that exhibit potential as inhibitors of the Bcr-Abl protein which could be utilized in chemotherapy. Herein, we evaluated and summarized 36 studies published in the last few years that reported on newly synthesized and biologically evaluated novel small molecules with different heterocyclic scaffolds as Bcr-Abl tyrosine kinase inhibitors. The intricacy of the structure of newly synthesized compounds and the fact that each compound contains more than one scaffold makes it difficult to infer the potentially active core or scaffold. However, investigating different combined scaffolds enhances the chance of successfully developing novel drug candidates. Overall, the information provided in this review can be beneficial to researchers with an interest in chronic myeloid leukemia and tyrosine kinase inhibitors.
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