Med Chem [JOURNAL]
Sun
200 papers
Characterization of the Cytotoxic Effect of Naphthalenacetamides Hydrochlorides on Cervical Cancer-Derived Cells.
Martinez-Nava C, Perez-Gonzalez C, Zavala-Sanchez MÁ … +3 more , Perez-Montiel EC, Lopez-Munoz FJ, Mendez-Cuesta CA
Med Chem · 2025 · PMID 40070144 · Publisher ↗
INTRODUCTION: Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but...
INTRODUCTION: Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but these are not always effective, which gives rise to the search for new compounds using cheminformatics tools. OBJECTIVE: The objective of this study was to design, synthesize, and biologically evaluate N-(2- morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)- N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) on the HeLa cell line . The referenced cell line from the American Type Culture Collection (ATCCCCL-2) was used, and the effect on cell viability was determined by MTT metabolic reduction-based assay at 24, 48, and 72 h. METHODS: Therapies directed at the σ1 receptor may be a treatment alternative since this receptor modulates the processes of cell proliferation and angiogenesis, producing cytoprotective or cytotoxic actions depending on the ligand with which it is coupled. RESULTS: The analysis showed that compounds 1 and 2 presented activity on HeLa cancer cells and viability at micromolar concentrations (1.923 μmol/mL and 0.374 μmol/mL, respectively). Moreover, the effect was maintained for 72 h. CONCLUSION: Naphthaleneacetamide derivatives exhibited an inhibitory effect on the HeLa cell line, and the OSIRIS program predicted less toxicity than cisplatin.
Application of Iodine-Amine Oxidation Approach in the Synthesis of Various N-Alkyl Phosphoramidate Oligonucleotide Derivatives.
Nekrasov MD, Pyshnyi DV, Kupryushkin MS
Med Chem · 2025 · PMID 40070143 · Publisher ↗
INTRODUCTION: Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful applicat...
INTRODUCTION: Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful application of different classes of phosphate modifications in the design of therapeutic oligonucleotides have led to a renewed interest in the development of approaches for introducing diverse classes of phosphate modifications. METHODS: This study aims to investigate the efficiency and optimize protocols for the application of the iodine-amine oxidation reaction to produce various N-alkyl phosphoramidate oligonucleotide derivatives during the conventional solid-phase phosphoramidite synthesis method. RESULTS: Various solvents and drying reagents were tested, and it was evaluated that even minor traces of water in a reaction mixture had a significant impact on yield. Using set of commercially available amines, it was shown that steric accessibility is a more critical parameter than nucleophilicity of the amino group in oxidative amination reaction. It was demonstrated that through use of amino alcohols and diamines during iodine-amine oxidation step various branched oligonucleotide structures can be synthesized. CONCLUSION: The obtained data indicates that the oxidative amination approach can be a promising tool for preparing various oligonucleotide derivatives during solid-phase synthesis without the use of specialized phosphoramidite monomers.
Exploring Phytochemicals as Potential Inhibitors of Cancer Cell Metabolic Pathways: A Computational Study.
Kapoor Y, Hasija Y
Med Chem · 2025 · PMID 40070142 · Publisher ↗
OBJECTIVE: The objective of this study is to explore the therapeutic potential of phytochemicals in cancer cell metabolism by investigating their ability to inhibit key molecular targets involved in tumor growth and drug...
OBJECTIVE: The objective of this study is to explore the therapeutic potential of phytochemicals in cancer cell metabolism by investigating their ability to inhibit key molecular targets involved in tumor growth and drug resistance. METHODS: We evaluated specific phytochemicals against critical cancer-related targets such as GLS1, CKα, MGLL, IDH1, PDHK1, and PHGDH. Molecular docking methods were used to understand the binding interactions between phytochemicals and their selected targets. ADME (absorption, distribution, metabolism, and excretion) analysis and molecular dynamics (MD) simulations were conducted to assess pharmacokinetic properties and ligand-protein interaction dynamics, respectively. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) calculations were utilized to estimate binding free energies. RESULTS: Molecular dynamics simulations demonstrate that phytochemicals like EGCG, Diosgenin, Withaferin A, and Celastrol exhibit stable binding to their respective targets, suggesting potential therapeutic benefits. Specifically, EGCG shows strong and non-toxic binding affinity with GLS1, making it a promising candidate for cancer treatment. CONCLUSION: Our study underscores the potential of phytochemicals as effective inhibitors of cancer cell metabolism. The stable binding interactions highlight promising avenues for developing innovative cancer therapies. Further experimental investigations are warranted to validate these findings and advance the development of hybrid phytochemical-based treatments for combating chemoresistance.
Emerging Role of Natural Topoisomerase Inhibitors as Anticancer agents.
Sahu SK, Vyas M, Prabhakar PK
Med Chem · 2025 · PMID 40070141 · Publisher ↗
Topoisomerases I and II are the functionally two forms of DNA topoisomerase. In anticancer research, novel anticancer chemotherapeutical capable of blocking topoisomerase enzymes have been discovered. Most commonly, topo...
Topoisomerases I and II are the functionally two forms of DNA topoisomerase. In anticancer research, novel anticancer chemotherapeutical capable of blocking topoisomerase enzymes have been discovered. Most commonly, topoisomerase causes replication fork arrest and doublestrand breaks, and this is how a clinically successful topoisomerase-targeting anticancer medicines work. Unfortunately, this novel mechanism of action has been linked to the development of secondary malignancies as well as cardiotoxicity. The specific binding locations and mechanisms of topoisomerase poisons have been identified by studying the structures of topoisomerase-drug-DNA ternary complexes. Recent breakthroughs in science have revealed that isoform-specific human topoisomerase II poison could be created as safer anticancer drug molecules. It may also be able to develop catalytic inhibitors of topoisomerases by focusing on their inactive conformations. In addition to this, the discovery of new bacterial topoisomerase inhibitor molecules and regulatory proteins could lead to the discovery of new human topoisomerase inhibitors. As a result, biologists, organic chemists, and medicinal chemists worldwide have been identifying, designing, synthesizing, and testing a variety of novel topoisomerase-targeting bioactive compounds. This review focused on topoisomerase inhibitors, their mechanisms of action, and different types of topoisomerase inhibitors that have been developed during the last ten years.
Benzimidazole Conjugates as Multi-target Anticancer Agents - A Comprehensive Review.
Remya RS, Ramalakshmi N, Aaliya MGS … +4 more , Concilia WB, Thasneem SF, Rohini S, Narmadha N
Med Chem · 2025 · PMID 40070140 · Publisher ↗
Cancer is the second leading cause of mortality globally and is characterized by a multifactorial etiology. Drug resistance and multidrug resistance are the reasons for the failure of many anticancer drugs that are in cl...
Cancer is the second leading cause of mortality globally and is characterized by a multifactorial etiology. Drug resistance and multidrug resistance are the reasons for the failure of many anticancer drugs that are in clinical practice now. The current review is a complete review of benzimidazole hybrids with different heterocyclic rings, which are potential anticancer agents. We reviewed around 70 research works of benzimidazole hybrids published in high-impact journals, along with a short discussion of structural features responsible for its activity against various cancers. This review highlighted benzimidazole hybrids as targeted anticancer agents with effects on multiple targets. Researchers working on targeted medications for cancer treatment will benefit from this review when designing new scaffolds with benzimidazole moieties.
Design and Synthesis of 3-(Phenylsulfonamido)benzamide Derivatives as Potent Carbonic Anhydrase IX Inhibitors: Biological Evaluations and Molecular Modeling Studies.
Khanfar MA, Saleh M
Med Chem · 2025 · PMID 40007186 · Publisher ↗
INTRODUCTION: Carbonic anhydrase IX (CAIX) is known to be overexpressed in various tumors and plays a significant role in tumor development and progression. METHODS: A series of 3-(benzylsulfonamido)benzamides derivative...
INTRODUCTION: Carbonic anhydrase IX (CAIX) is known to be overexpressed in various tumors and plays a significant role in tumor development and progression. METHODS: A series of 3-(benzylsulfonamido)benzamides derivatives was synthesized and tested for their CAIX inhibitory activities. The two most active compounds were subjected to cytotoxicity testing against a panel of 60 cancer cell lines. RESULTS: Many of the synthesized compounds successfully inhibited CAIX activities, exhibiting IC values in the low nanomolar range. The most potent CAIX inhibitor was compound 14, with an IC of 140 nM. Structure-activity relationship analysis of the synthesized compounds supported with molecular docking revealed strong coordination of sulfonamide moiety with the catalytic Zn metal, hydrophobic interactions of the benzylsulfonamido ring with a hydrophobic pocket, and π- stacking interactions of the aryl ring with an aromatic surface. The two most active analogues (10 and 14) were further tested for their antiproliferative activities in the NCI-60 human tumor cell lines. Notably, compound 14 demonstrated potent growth inhibitory effects against several cancer cell lines. CONCLUSION: The synthesized analogues represent a novel scaffold for the treatment of different types of cancer by targeting CAIX.
Studies of Phytoconstituents to Identify Potential Inhibitors for ERα Protein of Breast Cancer.
Alagarsamy V, Sulthana MT, Narendhar B … +5 more , Solomon VR, Parthiban P, Satishchandra A, Jothi LA, Murugesan S
Med Chem · 2025 · PMID 40007185 · Publisher ↗
BACKGROUND: It is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects....
BACKGROUND: It is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug leads for the treatment of breast cancer. OBJECTIVE: This study aims to discover and identify the potential inhibitors against the most influential ERα receptor by the computational approach of 134 phytochemicals from 17 medicinal plants by using docking studies. METHODS: The molecular docking was performed by a genetic algorithm using the Auto Dock Vina program, and the validation of docking was also performed by using Molecular Dynamic (MD) simulation by the Desmond tool of Schrödinger molecular modeling. Drug-likeness properties and toxicity studies were conducted using SWISS PRO. RESULTS: The top ten highest binding energy phytochemicals ginicidin (-10.8 kcal/mol), lemairone (-10.5 kcal/mol), ixoratannin (-10.0 kcal/mol), hydnocarpine (-9.8 kcal/mol), arabelline (-9.8 kcal/mol), acutilobine E (-9.8 kcal/mol), chaparinone (-8.9 kcal/mol), plumieride coumerate (-8.8 kcal/mol), acutilobine C (-8.7 kcal/mol), and mezerein (-8.7 kcal/mol) were taken for drug-likeness test and ADMET profile prediction with the help of web-based server SWISS ADME and protoxII. Docking's study dictated that ten phytochemical constituents showed greater binding interactions than standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. MSD study was achieved for the most active 4 phytoconstituents, and the stability of the ligand-protein complex was confirmed and showed that all the four compounds possess comparatively stable ligand-protein complexes with ERα target as compared to the tamoxifen-ERα complex. CONCLUSION: Among the top ten phytochemicals, ginicidin (glycoside) formed a more stable complex and had greater binding affinity than standard tamoxifen with better safety profiles. Hence, this compound can be further studied for lead optimization and drug development for the treatment of breast cancer.
New Approach as Inhibitor Against Head-Neck Cancer by In silico, DFT, FMOs, Docking, Molecular Dynamic, and ADMET of (Pencil Cactus).
Al Mashud MA, Devnath R, Anzuman M … +10 more , Sumona MI, Hossain MS, Kumer A, Talukder MEK, Rahman MM, Imon RR, Akash S, El Moussaoui A, Salamatullah AM, Bourhia M
Med Chem · 2025 · PMID 40007184 · Publisher ↗
BACKGROUND: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the s...
BACKGROUND: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. OBJECTIVES: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head- Neck cancer cells. MATERIALS AND METHODS: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood to assessments of their pharmacokinetics and ADMET. Finally, molecular dynamics simulations are employed to verify binding interactions and assess the stability of docked complexes. RESULTS: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. CONCLUSION: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and reduce the global burden of this disease.
Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features.
Mishra R, da Cunha Xavier J, Kumar N … +12 more , Krishna G, Dhakad PK, Dos Santos HS, Bandeira PN, Rodrigues THS, Gondim DR, Ribeiro WHF, da Silva DS, Teixeira AMR, Pereira WF, Marinho ES, Sucheta
Med Chem · 2025 · PMID 40007183 · Publisher ↗
OBJECTIVES: Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effecti...
OBJECTIVES: Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of and . METHODS: A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating and . The mechanism of action and SAR of these compounds were analyzed. RESULTS: Quinoline-based antimalarials demonstrated significant effectiveness in eliminating parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite's acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results. CONCLUSION: Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against and parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.
Exploring the Diverse Therapeutic Applications of 1, 3-Thiazine: A Comprehensive Review.
Agrawal N, Goyal D, Pathak S
Med Chem · 2025 · PMID 40007182 · Publisher ↗
Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine...
Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both and preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.
Design, Synthesis, Characterization, and Antitumor Activities of Benzimidazole-functionalized Organoruthenium Complexes Bearing Fluorine Group.
Pasahan R, Demirci O, Taskin II … +4 more , Pasahan A, Sever MR, Gok Y, Aktas A
Med Chem · 2025 · PMID 39950455 · Publisher ↗
BACKGROUND: This work presents the synthesis of Ru(II)NHC complexes bearing a series of 4-fluorobenzyl group. These complexes have been characterized by a variety of spectroscopic methods (H NMR, C NMR, and FTIR) and by...
BACKGROUND: This work presents the synthesis of Ru(II)NHC complexes bearing a series of 4-fluorobenzyl group. These complexes have been characterized by a variety of spectroscopic methods (H NMR, C NMR, and FTIR) and by elemental analysis techniques. METHODS: These complexes' antitumor activities against SH-SY5Y (human neuroblastoma) and (human colon cancer) were investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assay. RESULTS: The results showed that all the synthesized complexes exhibited significant cytotoxic effect with low IC values 15 ± 0.57, 15.26 ± 0.71, 7.64 ± 0.30, 27.66 ± 0.36 and 14.45 ± 0.84 (μg/mL) respectively. CONCLUSION: Furthermore, apoptosis assessed by double labeling with Annexin V-FITC/PI indicated that complexes 1b and 1d can effectively induce apoptosis and inhibit cell proliferation at the S phase in cells. Taken together, Ru(II)NHC complexes containing the 4- fluorobenzyl group have significant potential for the development of novel, highly effective anticancer agents.
Synergistic Warriors: Design and Synthesis of Dual-Acting Schiff-Based Threaded 1,2,3-Triazole Hybrids for Potent Antineoplastic and Anti-Mycobacterial Activities.
Walhekar V, Kulkarni R, Nuli MV … +7 more , Garige AK, Deore D, Pawar R, Patil A, Dvrn B, Santosh K, Kulkarni R
Med Chem · 2026 · PMID 39950454 · Publisher ↗
OBJECTIVE: In the pursuit of identifying divergent scaffolds for potential anticancer and anti-mycobacterial agents, a novel series of Schiff-based threaded 1,2,3-triazoles was designed and synthesized. METHODS: In this...
OBJECTIVE: In the pursuit of identifying divergent scaffolds for potential anticancer and anti-mycobacterial agents, a novel series of Schiff-based threaded 1,2,3-triazoles was designed and synthesized. METHODS: In this study, novel Schiff-based threaded 1,2,3-triazoles have been meticulously crafted and synthesized. Chemical structures of the synthesized molecules were confirmed by H NMR, C NMR and Mass spectra. Synthetic analogs were further evaluated for their antiproliferative, antitubercular and antimicrobial potentials by in vitro assays. RESULTS: The in vitro anti-tumor (anti-proliferative) evaluation on HT29 cancer cells revealed that compounds 8b and 8h exhibited remarkable inhibitory activity with IC50 values of 25 ± 0.8 and 24 ± 0.9 μM. In the context of anti-mycobacterial analysis, compound 8c demonstrated promising activity (6.25 μM) against H37Rv. Moreover, compounds 8d and 8e displayed equipotent antimicrobial potential (3.12 μM) comparable to Ciprofloxacin against both and . Molecular docking studies unveiled that 8c exhibited robust binding within the active pocket of carbonic anhydrase XII (docking energy -8.4 kcal/mol) and demonstrated a promising docking profile with β-ketoacyl ACP synthase I (docking energy - 9.5 kcal/mol) in the enzyme's binding pocket. CONCLUSION: Structure-activity relationship (SAR) analysis identified three pivotal pharmacophores; 1,2,3-triazole, aromatic ring system (substituted with halogens and -NO), and imine functionalities as crucial for the development of dual inhibitors targeting cancer and tuberculosis, showcasing an outstanding ADMET profile. Therefore, these compounds merit consideration as noteworthy pharmacological lead molecules in the realm of cancer and tuberculosis drug discovery and development.
Discovery of the PARP1 Inhibitors from Natural Compounds Using Structure-Based Virtual Screening and Bioactivity Evaluation.
Pan D, Huang Y, Jiang D … +4 more , Jin X, Wu M, Luo J, Zhang Y
Med Chem · 2026 · PMID 39950277 · Full text
BACKGROUND: PARP1 (poly ADP-ribose polymerase 1, also known as ADPRT1) plays a significant role in DNA repair and has become an attractive target for treating PARP1-related diseases, such as cancer. OBJECTIVE: This study...
BACKGROUND: PARP1 (poly ADP-ribose polymerase 1, also known as ADPRT1) plays a significant role in DNA repair and has become an attractive target for treating PARP1-related diseases, such as cancer. OBJECTIVE: This study aimed to discover inhibitors targeting PARP1 from the phytochemicals of Huangbai (Phellodendron chinense Schneid.), Baixianpi ( Turcz.), and Shechuangzi ( (L.) Spreng.). METHODS: The chemical compositions of Huangbai, Baixianpi, and Shechuangzi were extracted from the HERB database. Next, a combination of molecular docking and PARP1 enzyme assay was used to identify PARP1 inhibitors from these chemical components. Finally, molecular dynamics simulation and binding free energy calculation were used to explore the detailed interaction mode of these inhibitors with PARP1. RESULTS: A total of 507 chemical constituents of Huangbai, Baixianpi, and Shechuangzi were collected from the HERB database. Four potential PARP1 inhibitors were screened based on molecular docking and PARP1 enzyme assay. Demethyleneberberine exhibited strong PARP1 inhibitory activity with an IC value of 2.0 ± 0.8 μM. The IC values of the inhibitory activities of 8-hydroxy dictanmnine, meranzin hydrate, and osthol on PARP1 ranged from 44 μM to 76 μM. Molecular dynamics simulation and binding free energy calculation suggested that the nonpolar interaction energies of HIS862, GLY863, TYR889, TYR896, PHE897, and TYR907 played a primary role in the binding of inhibitors to PARP1. CONCLUSION: Integrating molecular simulation and bioactivity testing was found to be an effective approach for the rapid discovery of targeted PARP1 inhibitors. Demethyleneberberine demonstrated strong PRAP1 inhibitory activity and has a good prospect for development.
Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer.
Waseem HB, Shakeel M, Hassan FU … +8 more , Yaqoob A, Iqbal A, Khalid A, Akram HN, Dilbar N, Qamar S, Tahir RA, Sehgal SA
Med Chem · 2025 · PMID 39950276 · Publisher ↗
INTRODUCTION: Liver cancer is considered one of the most common types of cancer and a major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan Africa. The alpha-fetoprotein (AFP) is a...
INTRODUCTION: Liver cancer is considered one of the most common types of cancer and a major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan Africa. The alpha-fetoprotein (AFP) is a serum glycoprotein that belongs to a class of oncodevelopmental proteins and is also involved in tumor formation. METHODS: In the current effort, a hybrid approach of virtual screening followed by pharmacophore generation and molecular dynamic simulation analyses were performed. The screened top-ranked 10 docked compounds from the selected anti-cancer compound library were utilized to generate the ligand-based pharmacophore. Virtual screening was performed two-dimensional similarity search against the selected natural compound library based on their physicochemical properties. It was observed that all the compounds from the anti-cancer compound library and natural compound library showed similar binding resides. RESULTS: Therefore, the top-ranked screened compounds that showed the least binding energy and highest binding affinity against AFP, obtained through the anti-cancer drug library and natural compound library were reported. The molecular docking analyses revealed that Leu-219, His-222, Lys-242, Lys-246, His-316, Glu-318, Ala-366, Val-367, Gly-475, Ile-479, Ala-471, Asp-478 were observed as potential residues for interaction. CONCLUSION: The observed results of virtual screening, molecular docking, and MD simulation analyses entail noteworthy observations illustrating that NC002 was a potent inhibitor. The proposed compound NC002 may have potential against liver cancer by targeting AFP based on MD simulation analyses, PCA, and MM-GBSA.
Unlocking the Biological Potential of 2-Pyridones: Synthesis, Antioxidant and Antimicrobial Activity of N-Phenacylated 5/6-Chloro-2-pyridones.
Sangwan S, Chauhan S, Yadav N … +4 more , Kumar R, Duhan A, Malik V, Sindhu J
Med Chem · 2026 · PMID 39950275 · Publisher ↗
AIMS: A simple and efficient synthesis of 14 new (9a-9n) N-phenacyl-2-pyridones with good yields (up to 75%), is reported. The synthesized derivatives were screened for their in vitro radical scavenging activity against...
AIMS: A simple and efficient synthesis of 14 new (9a-9n) N-phenacyl-2-pyridones with good yields (up to 75%), is reported. The synthesized derivatives were screened for their in vitro radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), their in vitro antimicrobial potential was tested against human pathogenic bacterial strains, including , and , as well as the fungal strain Candida albicans. METHODS: All compounds displayed modest antioxidant activity, with compound 9b being the most potent in the DPPH radical scavenging assay. Most of the synthesized compounds exhibited good to excellent antimicrobial activity, however, the compounds (9d, and 9b) showed maximum inhibition zone diameters of 18.75, and 18.25 mm respectively, demonstrating better antimicrobial potential than the standard drug streptomycin against . RESULTS: Compound 9f was found most effective against with a 23.25 mm zone of inhibition against a 17.50 mm zone of inhibition of the standard, streptomycin. Molecular docking of the compounds 9d and 9f with tyrosyl-tRNA synthetase revealed good binding with the target. CONCLUSION: The electron-withdrawing substituents on the aryl ring of synthesized N-phenacyl-2- pyridones improved the antioxidant activity, however, for Gram-positive bacteria, less lipophilic or more hydrophilic substituents, such as halogens, displayed better antimicrobial activity. Similarly, it was the more lipophilic substitutions on the aryl ring that improved the antimicrobial activity against Gram-negative bacteria.
Bioactive Compounds from : Antioxidant Insights and Docking Studies on HK-ATPase and H Receptor Targets.
Pathak R, Chandra P
Med Chem · 2026 · PMID 39917935 · Publisher ↗
BACKGROUND: (Myricaceae) are common in the Indian Himalayas. Traditional medicine uses it to treat chronic bronchitis, inflammation, stomach ulcers, anaemia, diarrhoea, asthma, and ear, throat, and nose disorders. Its v...
BACKGROUND: (Myricaceae) are common in the Indian Himalayas. Traditional medicine uses it to treat chronic bronchitis, inflammation, stomach ulcers, anaemia, diarrhoea, asthma, and ear, throat, and nose disorders. Its varied medicinal benefits are recognised in the ayurvedic pharmacopoeia. AIMS: Isolation of Bioactive Compounds from M. esculenta: Assessment of Antioxidant Activity and Molecular Docking Studies Targeting the HK-ATPase enzyme and H Receptor. MATERIALS AND METHODS: The fruit of the Myrica esculenta plant was extracted. The total phenolic and total flavonoid content of the extract were determined. Following column chromatography, two phytoconstituents were identified by mass spectroscopy, FTIR, and NMR. The antioxidant activity of phytoconstituents was evaluated using the DPPH Scavenging Assay, Reactive Nitrogen Oxide Scavenging Assay, and Hydroxyl Free Radical Scavenging Assay. Then, molecular docking studies were performed against the HK-ATPase enzyme and H Receptor. RESULTS: The research successfully extracted methanolic extract from M. esculenta by maceration, which yielded rich in flavonoids and phenolic content and isolated compounds using column chromatography, which was further characterized to be myricetin and catechin using Mass spectroscopy, FTIR, and NMR. The further evaluation of the antioxidant activity of compounds demonstrated significant activity with IC value indicating strong free radical scavenging activity. Molecular docking studies were performed against the HK-ATPase enzyme and H Receptor, revealing that both the compounds exhibit high binding affinity and favorable interactions with key sites. CONCLUSION: The findings suggest that the isolated compounds myricetin and catechin possess potential antioxidant activity and could be a potential therapeutic target for the HK-ATPase enzyme and H Receptor.
Exploring Structural Requirement of Curcumin-Based CK2 Inhibitors as Anticancer Agents: 3D-QSAR, Pharmacophore Modeling, Virtual Screening, and Molecular Docking.
Fatima F, Nema P, Garhwal A … +1 more , Kashaw SK
Med Chem · 2025 · PMID 39917934 · Publisher ↗
INTRODUCTION: Casein Kinase 2 (CK2), discovered as one of the earliest protein kinases, is a ubiquitous Ser/Thr protein kinase-specific to acidic environments. CK2 has been implicated in regulating diverse cellular proce...
INTRODUCTION: Casein Kinase 2 (CK2), discovered as one of the earliest protein kinases, is a ubiquitous Ser/Thr protein kinase-specific to acidic environments. CK2 has been implicated in regulating diverse cellular processes and has been linked to the onset of various diseases, including cancer. METHODS: Consequently, modulating CK2 function has emerged as a potential therapeutic strategy. However, currently, available CK2 inhibitors or modulators often lack sufficient specificity and potency. RESULTS: The results were validated through QSAR of curcumin derivatives, Pharmacophore modeling, virtual screening performed for filtered curcumin-like featured derivatives from the database, and Molecular Docking approaches. Since there is a solved crystal structure of high-resolution Xray crystal structures of Human protein kinase CK2 alpha in complex with ferulic aldehyde. CONCLUSION: Also, structure-based virtual screening was performed against a total of 3253 compounds from different libraries, and only the top 4 best-hit compounds with exceptional docking scores exceeding > -7 kcal/mol (more than 7 kcal/mol) were screened and analyzed. However, to validate their therapeutic potential, these compounds require evaluation to assess their CK2 targeting ability.
Docking and Molecular Dynamics Studies on Anticancer Activities of Flavonoids as Inhibitors of CDK2 and CDK9.
Sony AS, Suresh MX
Med Chem · 2025 · PMID 39916437 · Publisher ↗
BACKGROUND: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using studies. OBJECTIVE: In this article, studies were carried out to fi...
BACKGROUND: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using studies. OBJECTIVE: In this article, studies were carried out to find promising anticancer lead among selected flavonoid compounds. METHODS: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. RESULTS: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. CONCLUSION: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.
Synthesis and Evaluation of Antibacterial and Antifungal Activities and of Novel Morpholinoalkoxychalcones.
Phan HM, Mai TT, Don TNQ … +5 more , Do DT, Thai KM, Tran TD, Truong P, Huynh PNH
Med Chem · 2025 · PMID 39916436 · Publisher ↗
INTRODUCTION: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioac...
INTRODUCTION: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. METHODS: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. RESULTS: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against , with an MIC value of 0.6 mM. B.43 with an MIC value of 2.04 mM has displayed its potential in inhibiting and the best among other compounds. CONCLUSION: The study has revealed two targets to align with the results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH, and halogen groups on both rings A and B.
Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance.
Mishra I, Sharma V, Kumar N … +5 more , Krishna G, Sethi VA, Mittal R, Dhakad PK, Mishra R
Med Chem · 2025 · PMID 39916435 · Publisher ↗
OBJECTIVES: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of...
OBJECTIVES: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions. METHODS: A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of and studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions. RESULTS: Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship. CONCLUSION: The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.
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