Med Chem [JOURNAL]
Sun
200 papers
Recent Advances in Anticancer Research of Osmium and Rhodium Complexes.
Kostova I
Med Chem · 2025 · PMID 41368775 · Publisher ↗
Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug res...
Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.
Design, Synthesis, and Biological Evaluation of Novel 7-Hydroxycoumarin- Based -Hydroxyamides as Histone Deacetylase Inhibitors and Cytotoxic Agents.
Thanh TD, Thach VX, Chinh LV … +5 more , Anh DTP, Thao DT, Quy DQ, Pham-The H, Vu TK
Med Chem · 2025 Nov · PMID 41185501 · Publisher ↗
INTRODUCTION: Histone deacetylases (HDACs) play a crucial role in gene expression, and their dysregulation is linked to various cancers. HDAC inhibitors, particularly hydroxamic acid derivatives, have shown promising ant...
INTRODUCTION: Histone deacetylases (HDACs) play a crucial role in gene expression, and their dysregulation is linked to various cancers. HDAC inhibitors, particularly hydroxamic acid derivatives, have shown promising anticancer effects, with several approved for clinical use. This research aimed to synthesize novel 7-hydroxycoumarin-based N-hydroxyamides, evaluate their HDAC inhibition, and assess their in vitro cytotoxic effects. METHODS: The structures of the synthesized compounds were established by analysis of their physicochemical, elemental, and spectroscopic data. HDAC, in vitro assays, and molecular docking were performed using standard procedures. RESULTS: The biological results showed that compounds 5d, 5e, 5j, 5l, and 7k exhibited potential cytotoxicity toward all five cancer cell lines. These compounds displayed potent cytotoxicity against the NCCIT cancer cell line with IC50 values of 4.53-1.45 μM. However, they exhibited weak to medium HDAC inhibitory activity with IC50 values ranging from 21.72 to 4.79 μM. Docking simulation studies with selected compounds revealed that compounds 5a and 7k formed stable interactions in the active site of HDAC enzyme with binding affinities ranging from -7.43 to -7.103 kcal/mol, respectively. DISCUSSION: The study revealed several compounds with potential HDAC inhibitory activity and cytotoxicity. However, they were still less effective in inhibiting HDACs than SAHA and Trichostatin A. Their reduced potency may be related to the length of the linker linked to the surface recognition group. This provides important insight into the future design of hydroxamic acids of this type. CONCLUSION: The research results suggest that some hydroxamic acids (5a and 7k) warrant further evaluation, and these results could serve as a basis for designing more potent HDAC inhibitors and antitumor agents.
Virtual Screening of FDA-Approved Drugs on Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) to Obtain New Trypanocidal Agents.
Juarez-Saldivar A, Vazquez-Jimenez LK, Ortíz-Pérez E … +3 more , Gomez-Escobedo R, Nogueda-Torres B, Rivera G
Med Chem · 2025 Oct · PMID 41133831 · Publisher ↗
INTRODUCTION: The protozoan parasite Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease, also known as American trypanosomiasis, which primarily affects the Americas and is highly prevalent in developi...
INTRODUCTION: The protozoan parasite Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease, also known as American trypanosomiasis, which primarily affects the Americas and is highly prevalent in developing countries. Treatment consists of the drugs nifurtimox and benznidazole; however, both drugs have variable efficacy and cause serious adverse effects. In T. cruzi, the enzyme glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH) plays an essential role in energy production and additional nuclear functions, making it a pharmacological target for the development of new trypanocidal agents. In this study, the objective was to identify new potential TcGAPDH inhibitors with trypanocidal activity. METHODS: A virtual screening based on molecular docking of FDA-approved drugs was performed, followed by in vitro biological evaluation of trypomastigotes from two T. cruzi strains. RESULTS: Seven FDA-approved drugs (pemetrexed, gliquidone, irbesartan, enoxacin, norfloxacin, pazopanib, and fenoprofen) had the best affinity values and a suitable interaction profile at the active site of the TcGAPDH enzyme, which had better LC50 values than the reference drugs. DISCUSSION: Drug repositioning using computer-aided methods reduces cost and time to find new pharmacological treatments. In this study, gliquidone (antidiabetic), irbesartan (antihypertensive), pemetrexed, and pazopanib (anticancer) are drugs with high trypanocidal activity that could be candidates for evaluation in clinical phases or used to develop new drugs to combat Chagas disease. It highlights fenoprofen, an anti-inflammatory agent, which has biological properties that help to reduce the symptomatology of the disease in the chronic stage. Additionally, it is necessary to study the mechanism of action of these compounds in detail to confirm if they have an effect on the proposed pharmacological targets. CONCLUSION: Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease.
Quinolones: The Cornerstone of the Advanced Era in Therapeutics.
Choudhary P, Bhatti M
Med Chem · 2025 Oct · PMID 41121519 · Publisher ↗
Quinolones are nitrogen-containing heterocyclic compounds that exist in natural, semisynthetic, and synthetic forms, and play a vital role as antibiotics. Their complex structure and numerous potential modifications have...
Quinolones are nitrogen-containing heterocyclic compounds that exist in natural, semisynthetic, and synthetic forms, and play a vital role as antibiotics. Their complex structure and numerous potential modifications have made them a significant focus in synthetic chemistry over the past two to three decades. The most common compound associated with quinolones is nalidixic acid, which was discovered long ago. Since then, various researchers have focused on this core as a potential pharmacophore or starting nucleus for developing new drug candidates to manage diseases, such as cancer, urinary tract infections, Alzheimer's, and tuberculosis. In this paper, we aimed to summarize the activities of quinolone hybrids discovered over the past decades. The article delivers a thorough overview of quinolones with emphasis on synthetic innovations, their mechanism of action, resistance evasion, and classification from generation to generation, along with the newer agents. Furthermore, emerging concepts, including modulation of SOS response, induction of oxidative stress, and impact of sub-inhibitory concentrations, are also explored as supplementary strategies to enhance antibacterial efficacy. Beyond their well-known antibacterial activity, quinolones also exhibit a broad range of pharmacological properties, including antimalarial, antifungal, antiinflammatory, antitubercular, anticancer, antiviral, and immunomodulatory effects. This review highlights both their diverse clinical applications and the challenges associated with their use. This article also provides a knowledgeable asset for acknowledging quinolones' chemistry, pharmacology, and future therapeutic potential.
Oxindole Analogues as Anticancer Agents and their Therapeutic Potential.
Pathak S, Sharma K, Goswami A … +1 more , Singh P
Med Chem · 2025 Oct · PMID 41121518 · Publisher ↗
Oxindole and its derivatives have emerged as interesting scaffolds for developing innovative anticancer medicines due to their various biological activities and capacity to target critical molecular pathways in cancer gr...
Oxindole and its derivatives have emerged as interesting scaffolds for developing innovative anticancer medicines due to their various biological activities and capacity to target critical molecular pathways in cancer growth. The oxindole nucleus has powerful anticancer capabilities, which are exerted through various methods, including kinase inhibition, apoptosis induction, disruption of microtubule dynamics, and signaling pathway modification (PI3K/Akt, MAPK, and p53). Furthermore, oxindole-based drugs have been beneficial in combating multidrug resistance and improving the efficacy of existing chemotherapeutic treatments. The current review examines the anticancer potential of the oxindole nucleus, including structure-activity correlations, molecular targets, and methods of action. Furthermore, we discuss current advances in oxindole-derived drug design and its clinical implications, providing insights into prospective therapeutic possibilities. Understanding the molecular characteristics of oxindole derivatives can help in the rational development of new anticancer medicines with higher efficacy and selectivity.
Unveiling the Therapeutic Potential of 8-Hydroxyquinoline: A Multi-Targeting Approach.
Patel R, Shah D, Patel A
Med Chem · 2025 Oct · PMID 41114489 · Publisher ↗
In recent years, extensive research has been conducted by medicinal and organic chemists on derivatives of 8-Hydroxyquinoline (8-HQ) due to their potential as therapeutic agents for a wide range of diseases and disorders...
In recent years, extensive research has been conducted by medicinal and organic chemists on derivatives of 8-Hydroxyquinoline (8-HQ) due to their potential as therapeutic agents for a wide range of diseases and disorders. These derivatives show promise in treating conditions such as cancer, HIV, tuberculosis, and neurodegenerative disorders. Additionally, the ability of 8-HQ to chelate metal ions adds to its value as a scaffold for developing treatments for various diseases. Over the past two decades, significant efforts have been made to create drug molecules based on 8- HQ that exhibit excellent therapeutic potency against different therapeutic targets. Recognizing the significance of 8-HQ in the field of therapeutics, this review provides an overview of its reported therapeutic activity in the literature over the past two decades. The review also addresses the challenges and opportunities in the development of 8-HQ, suggesting future research directions in this area.
Hypolipidemic and Hepatoprotective Effects of 5-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)Pentanoic Acid (TDPPA) on Hyperlipidemic Mice.
Li T, Liu M, Yuan Q … +4 more , Shen W, Chen X, Zhang L, Xie Y
Med Chem · 2025 Oct · PMID 41088933 · Publisher ↗
INTRODUCTION: Hyperlipidemia is a prevalent condition that accelerates the development of cardiovascular diseases. Traditional treatments targeting lipid regulation often have limitations, such as hepatotoxicity. This st...
INTRODUCTION: Hyperlipidemia is a prevalent condition that accelerates the development of cardiovascular diseases. Traditional treatments targeting lipid regulation often have limitations, such as hepatotoxicity. This study investigates the dual action of a novel compound, 5-(4-(3-thioxo- 3H-1,2-dithiol-5-yl)phenoxy)pentanoic acid (TDPPA), in reducing lipid levels and protecting the liver. METHODS: TDPPA was synthesized and structurally confirmed by 1H-NMR, 13C-NMR, and HRMS. Its lipid-lowering efficacy was first assessed in Triton WR-1339-induced acute hyperlipidemic mice. Mechanistic studies were then conducted in a high-fat emulsion-induced chronic hyperlipidemia model, incorporating histopathological analysis of the liver (H&E and Oil Red O staining). Liver index, serum lipid panels, hepatic function markers, HⁿS content, oxidative stress parameters, and pro-inflammatory cytokines were quantified via ELISA, while the interaction between TDPPA and PPAR-α was evaluated by molecular docking and Western blotting. RESULTS: TDPPA significantly reduced serum triglyceride (TG), total cholesterol (TC), and lowdensity lipoprotein cholesterol (LDL-C) in both acute and chronic models, while increasing highdensity lipoprotein cholesterol (HDL-C). Histology revealed marked reductions in hepatic lipid accumulation and inflammatory infiltration. Biochemical assays showed decreases in AST and ALT, enhanced antioxidant capacity (higher SOD and HⁿS, lower MDA), and suppression of TNF- α, IL-6, and IL-1β. Molecular docking and Western blot analysis indicated that these effects were associated with upregulation of PPAR-α protein expression. DISCUSSION AND CONCLUSION: TDPPA demonstrates potent lipid-lowering, antioxidant, and antiinflammatory activities, likely through a dual mechanism involving PPAR-α activation and HⁿSmediated hepatoprotection. These findings position TDPPA as a promising therapeutic candidate for hyperlipidemia with the benefit of liver protection.
Virtual Screening of HBV Capsid Assembly Modulators with the Combination of Pharmacophore Modeling and Hydrogen Bond Constraints.
Zhao H, Wang Y, Yan H … +3 more , Yu Y, Xu L, Sheng R
Med Chem · 2025 Oct · PMID 41088932 · Publisher ↗
INTRODUCTION: Hepatitis B virus (HBV) infection remains a significant public health challenge. Targeting HBV capsid assembly has the potential to achieve a functional cure for HBV infection, and the capsid assembly modul...
INTRODUCTION: Hepatitis B virus (HBV) infection remains a significant public health challenge. Targeting HBV capsid assembly has the potential to achieve a functional cure for HBV infection, and the capsid assembly modulators (CAMs) have been regarded as promising therapeutic agents for HBV. In this work, we aimed to identify novel scaffold HBV CAMs through a multi-step virtual screening approach. METHODS: Pharmacophore-based virtual screening combined with hydrogen bond constraints was performed on the Specs and ChemDiv databases. Potential modulators were screened using qPCR (quantitative PCR) and CCK-8 assays. Molecular dynamics (MD) simulations and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis were employed to evaluate ligand-protein binding modes and pharmacokinetic properties. RESULTS: Twenty-one compounds were selected as potential HBV CAMs. Compounds B5, B19, and B21 exhibited excellent anti-HBV activity, with EC50 values of 1.74, 4.29, and 0.38 μM, respectively. MD simulations revealed their possible binding modes with the HBV core protein, confirming the critical role of Trp102-mediated hydrogen bonds. DISCUSSION: Hydrogen bonds are critical for establishing stable and high-affinity interactions between small molecules and targets. Three compounds, B5, B19, and B21, were identified as novel scaffold hits of CAMs through virtual screening with the combination of pharmacophore modeling and hydrogen bond constraints. MD simulations illustrated the critical contributions by Trp102, providing valuable insights for further structural optimization. CONCLUSION: Compounds B5, B19, and B21 can serve as promising starting points for the development of more potent anti-HBV candidates through future hit-to-lead optimization.
Stereoisomerism in Chemistry and Drug Development: Optical, Geometrical, and Conformational Isomers.
Chawla S, Gupta R, Jha SK … +3 more , Shamim, Kashid S, Jha KT
Med Chem · 2025 Oct · PMID 41051049 · Publisher ↗
Stereoisomerism in addition to conformational, geometrical, and optical isomerism, has considerable effects on the stability, reactivity, and functioning of molecules. Therefore, the objective of this article is to revie...
Stereoisomerism in addition to conformational, geometrical, and optical isomerism, has considerable effects on the stability, reactivity, and functioning of molecules. Therefore, the objective of this article is to review the recent developments and research on stereoisomerism, including its consequences in various branches of science. The energetics and stability of conformational isomerism, which depict the concept of cis-trans and E/Z configurations of geometric isomerism, elucidate the molecular behavior and the efficacy of drugs, also discussed. The consequence of stereochemistry on pharmacology and drug design is elucidated by optical isomerism in terms of chirality and enantiomorphic effects. To exemplify the use of stereoisomerism in drug development, this review, offers wide case studies of NSAIDs, anticancer drugs, and antibiotic drugs. In this Article, the phenomenon of stereoisomerism is also primarily discussed concerning biomolecules such as proteins, carbohydrates, lipids, and nucleic acids. Recent advances in comparison operations include computer-aided drug design, advances in personalized medicine, and new therapies such as DNA and peptide drugs, including their possible impacts on the business and natural world. The primary aim of the review is to thoroughly investigate and examine stereoisomerism and its wide-ranging implications.
Preface.
Hadjipavlou-Litina D
Med Chem · 2026 · PMID 41029011 · Publisher ↗
Abstract loading — click title to view on PubMed.
A Step Towards Development and Bio-evaluation of a Novel Radio-ligand Tc-CYX-DTPA Targeting Sigma 2 Receptors.
Chaudhary R, Chaturvedi S, Gautam D … +6 more , Chaudhary V, Sharma D, Presenjit, Garg A, Chopra M, Mishra AK
Med Chem · 2025 · PMID 41001800 · Publisher ↗
INTRODUCTION: Development of theranostics agents targeted towards particular receptors can effectively help in the management of cancer. The overexpression of the sigma-2 receptor (S2R) in tumors establishes it as a prom...
INTRODUCTION: Development of theranostics agents targeted towards particular receptors can effectively help in the management of cancer. The overexpression of the sigma-2 receptor (S2R) in tumors establishes it as a prominent biomarker for cancer cells. METHODS: Radiotheranostics rely on the design of specific molecules having versatility in applications of diagnosis and therapy by merely changing the radioisotope. We have designed a novel radiotheranostic S2R-targeted ligand using cyclohexylpiperazine and performed docking studies to narrow down the potential efficacious ligand. The potential molecule with G-score = -7.0 kcal/mol, was then synthesized using a three steps reaction including conjugation of 2-(4- cyclohexylpiperazine-1-yl)ethyl(CYX) with DTPA chelator. Subsequently, the molecule has been radiolabelled with Tc using stannous chloride as a reducing agent, and a radiolabellieng efficiency of 95.0 ± 0.59% for Tc-CYX-DTPA. As proof of concept, the molecule has been evaluated for its binding affinity and specificity using sigma receptors isolated from the liver membrane homogenates of mice. The binding affinity was found to be K = 12.84 ± 0.395 nM; B = 0.5258 ± 0.001 fmol/mg, indicating a high affinity for the receptors. RESULTS: In addition, the molecule was also assessed for biocompatibility using haemolysis analysis and cytotoxicity on HEK cells and MDA-MB-23, wherein the molecule showed no significant cytotoxicity up to 72 h on HEK cells and 32.42% cytotoxicity on MDA-MB-231 cells. CONCLUSION: The future work will concentrate on the demonstration of targeting and sitespecific accumulation of the molecule along with its suitability for theranostics applications.
Study of Novel Tryptanthrin-Based Topoisomerase Inhibitors.
Kumawat MK, Kumar K
Med Chem · 2025 · PMID 41001799 · Publisher ↗
BACKGROUND: Over the past ten years, a remarkable number of changes have occurred in the field of cancer drug research. Most anticancer drugs from the first generation work by breaking down DNA, preventing its production...
BACKGROUND: Over the past ten years, a remarkable number of changes have occurred in the field of cancer drug research. Most anticancer drugs from the first generation work by breaking down DNA, preventing its production, interfering with cell division processes, or attaching to microtubules. The potential use of tryptanthrin as well as its analogues is well documented for anticancer properties. OBJECTIVE: To design a novel hybrid of tryptanthrin analogs with expected anticancer activity. METHODS: By changing the C-6 carbonyl position of the tryptanthrin molecule, a set of 72 derivatives of substituted-6-benzylidine-6H-indolo[2,1-b] quinazoline-12-one was developed. These ligands were screened using Schrodinger Glide extra precision docking against DNA topoisomerase using doxorubicin and teniposide as references to identify their potential anticancer properties. Further, these ligands were subjected to an ADMET study to identify their drug likeliness. RESULTS: Combined results of molecular docking and ADMET study suggest that out of the total 72 ligands, 6 ligands RC 51, RC 29, RC 42, RC 3, RC 54, and RC 63 were showing very better binding affinity than the natural ligand adenylyl-imidodiphosphate and the two standard reference drugs- doxorubicin and teniposide. CONCLUSION: Our computational approach was successful in identifying ligands that are potentially potent topoisomerase inhibitors. These can be tested further using and analysis.
Drug Design and Repurposing to Suppress Liver Cancer VEGF-R1 Mechanism: Comprehensive Molecular Docking, Molecular Dynamics Simulations and ADME Estimation.
Agar S
Med Chem · 2025 · PMID 41001798 · Publisher ↗
AIM: The aim is to halt the progression of liver cancer (Hepatocellular carcinoma) by suppressing the VEGF-R1 receptor using Myricetin and its -designed analogues. BACKGROUND: VEGF/VEGFR autocrine signalling promotes the...
AIM: The aim is to halt the progression of liver cancer (Hepatocellular carcinoma) by suppressing the VEGF-R1 receptor using Myricetin and its -designed analogues. BACKGROUND: VEGF/VEGFR autocrine signalling promotes the growth, progression, and metastasis of Hepatocellular carcinoma, making the development of molecularly targeted therapies highly feasible. Invasive and metastatic behaviours in various cancers, including hepatocellular carcinoma (HCC), are closely monitored through the use of VEGF signalling pathway inhibitors. Specifically in HCC, VEGFR-1 facilitates the invasive capabilities of cancer cells primarily by triggering the epithelial-mesenchymal transition (EMT) process. VEGFR-1 significantly influences the activity of proteolytic enzymes that are critical for the invasive behaviour of HCC cells. Notably, a novel mechanism has been discovered where VEGFR-1 activation leads to the upregulation of MMP-9, thereby enhancing the invasiveness of HCC cells. The scientists, in their study, have elaborated on the various antiangiogenic agents developed for the treatment of HCC. They have highlighted clinical trials that explore the efficacy of these treatments, which include the application of monoclonal antibodies and small-molecule kinase inhibitors designed to target specific pathways involved in tumour angiogenesis and growth. OBJECTIVE: Creating a pharmaceutical chemistry table regarding "Structure-Activity Relationship of New Compounds on anticancer''. To do so, Myricetin and its designed structured variants were used in molecular docking, molecular dynamics, cluster analyses, and 1H NMR estimation to specifically understand and enhance the mechanism of suppressing the VEGF-R1 receptor. METHODS: Proper ligands (Myricetin and its analogues) and receptor (VEGF-R1) preparations, and optimizations were done using the density functional theory (DFT)/B3LYP function along with the 6-31G(d,p) basis set principle in the latest software programs such as Gaussian 09, Gauss View 6.0 and Avogadro. Then using PyRx and Autodock Vina 1.1.2., many molecular docking trials were achieved with 100 posed simulations in each run. An extensive cluster analysis was performed to identify the most optimal docking poses with the highest accumulation and most favourable binding interactions, ensuring the accuracy of the study. The docking configurations that exhibited the most precise and accurate poses with lowest inhibition constants were chosen as initial structured data for subsequent Molecular Dynamics (MD) simulations for each drug candidate. To verify the molecular docking results, MD runs were achieved in our supercomputers and the trajectory analyses were made. The data confirmed what was found in molecular docking results, verifying the high efficiency of the druggable molecules' inhibition towards VEGF-R1. RESULTS: Amine-derivatized Myricetin has a significantly high docking score (-10.56 kcal/mol) and great inhibition constant compared to pristine Myricetin (-4.77 kcal/mol) itself while Fluorinederivatized Myricetin (-6.45 kcal/mol) has an affinity towards VEGF-R1 between the first two molecules. Thus, the structure-activity relationship concerning pharmaceutical chemistry aspects of all the molecules studied, yielded us a great insight into what Myricetin's organic structure possesses towards inhibiting the progression of Liver Cancer. Also, ADME studies showed that both Amine and Fluorined-derivatized Myricetin molecules are good drug candidates. CONCLUSION: This study highlighted the significant potential of Myricetin as an anti-cancer drug when modified with specific functional groups. Through comprehensive computational analyses, our research group enhanced Myricetin's inhibitory capabilities by derivatizing its Hydroxyl group with Amine and Fluorine, resulting in improved docking scores and inhibition constants. The findings from molecular docking and MD simulations provide a promising foundation for future and investigations of these molecules as potential drugs in cancer research.
Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.
Banerjee S, Baidya SK, Jha T … +2 more , Ghosh B, Adhikari N
Med Chem · 2025 · PMID 41001797 · Publisher ↗
HDAC8 is associated with several disease conditions as well as various cancers of several organs and hematological malignancies. To counter such pathophysiological and disease conditions, inhibition of HDAC8 may be a pro...
HDAC8 is associated with several disease conditions as well as various cancers of several organs and hematological malignancies. To counter such pathophysiological and disease conditions, inhibition of HDAC8 may be a promising approach for anticancer drug development. In this article, a detail of arylcarboxamide-based potential HDAC8 inhibitors has been outlined. Considering their binding pattern of interactions along with the chemical features, effective and selective novel HDAC8 inhibitors can be designed further. Therefore, modification of these compounds provides greater possibilities for the development of novel HDAC8 inhibitors. Nevertheless, structural modification of such arylcarboxamide derivatives may be able to produce potent dual-inhibitory compounds along with HDAC8 inhibition. Thus, this article is quite useful for exploring and identifying several possibilities for arylcarboxamide-based HDAC8 inhibitors. Moreover, it can be concluded that further study of the arylcarboxamide-based HDAC8 inhibitors can be effectively used for the treatment of different cancerous and non-cancerous diseases.
Unveiling the Anti-cancer Potential of Oxadiazole Derivatives: A Comprehensive Exploration of Structure-Activity Relationships and Chemico-Biological Insights.
Mishra SS, Samanta A, Paul A … +2 more , Maji A, Maity TK
Med Chem · 2025 · PMID 41001796 · Publisher ↗
BACKGROUND: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Fura...
BACKGROUND: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. OBJECTIVE: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SwissADME tool have to be studied. RESULTS: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. CONCLUSION: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.
Evaluation of -Toluenesulfonyl Hydrazones as Anti- and Leishmanicidal Agents.
Caridad E, Delgado-Maldonado T, Navarrete-Carriola DV … +6 more , Vázquez-Jiménez LK, Ortiz-Perez E, Paz-González AD, Martinez I, Espinoza B, Rivera G
Med Chem · 2025 Sep · PMID 40968427 · Publisher ↗
INTRODUCTION: Neglected tropical diseases (NTDs), such as Chagas disease (CD) and Cutaneous Leishmaniasis (CL), are significant global health concerns. The limited number of treatments and their severe adverse effects wo...
INTRODUCTION: Neglected tropical diseases (NTDs), such as Chagas disease (CD) and Cutaneous Leishmaniasis (CL), are significant global health concerns. The limited number of treatments and their severe adverse effects worsen the situation. Therefore, the development of molecules as a new pharmacological alternative is necessary. This work aimed to obtain new p- Toluenesulfonyl hydrazones derivatives to determine their potential antiparasitic activity against and . METHODS: Compounds were synthesized by condensing p-Toluenesulfonyl hydrazide with aromatic aldehydes using acetic acid as a catalyst. All compounds were structurally elucidated using infrared (IR) spectroscopy, proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), and Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry (UPLCMS). The Queretaro (Qro) strain of and the M379 strain of were used for assays. RESULTS: Compound pT-21 (IC= 49.6 μM) was the most active agent against the Qro strain. Meanwhile, compounds pT-15 and pT-21 inhibited the proliferation of promastigotes with an IC value of 59.2 and 13.8 μM, respectively. In addition, these compounds had low cytotoxic effects against Vero cell lines (CC values >100 μM). DISCUSSION: In this study, compound pT-21 inhibited the proliferation of and . Its activity is attributed to the reactivity of the 5-nitrofuran ring (present in other drugs such as nifurtimox). Future research could focus on identifying the pharmacological target of compound pT-21 to facilitate rational drug design and enhance its potency against these parasites. CONCLUSION: In summary, these results show that p-Toluenesulfonyl hydrazones serve as a scaffold to aid in the development of potent and selective agents against and .
Discovery of Novel 1,3,4-oxadiazole-based Inhibitors Against Urease and Diabetes: Design, Synthesis, SAR, Biological, and Molecular Docking Screening.
Arshad S, Maalik A, Rehman W … +6 more , Khan Y, Sarfraz H, Rasheed L, Hawsawi MB, Alluhaibi MS, Alharbi M
Med Chem · 2025 Sep · PMID 40965024 · Publisher ↗
INTRODUCTION: Heterocyclic compounds bearing oxygen and nitrogen atoms are key pharmacophores in modern drug design. Among them, 1,3,4-oxadiazoles are notable for their diverse biological activities, including anti-infla...
INTRODUCTION: Heterocyclic compounds bearing oxygen and nitrogen atoms are key pharmacophores in modern drug design. Among them, 1,3,4-oxadiazoles are notable for their diverse biological activities, including anti-inflammatory, anticancer, antidiabetic, antibacterial, and enzyme inhibitory effects. This study focuses on the synthesis and evaluation of indazole-based 1,3,4-oxadiazole-benzenesulfonothioate hybrids as potential therapeutic agents. METHOD: A multistep synthetic route was employed to develop a series of eighteen (18) analogues. The synthetic strategy involved the formation of methyl 5-methyl-1H-indazole-3-carboxylate, conversion to carbohydrazide, cyclization with CS, and final coupling with substituted benzenesulfonyl chlorides to yield the target hybrids (1-18). RESULTS: The urease inhibition potential of scaffolds ranged from IC = 17.88 ± 0.36 to 37.98 ± 0.80 μM as compared to the standard drug thiourea (IC = 29.45 ± 0.76 μM). The exceptional urease and α-glucosidase activity was shown by scaffolds (4, 7, 9, 11) due to the presence of electron- withdrawing groups (-F, NO, and Cl). In comparison, the α-glucosidase inhibition potential shown by all the scaffolds was in the range (IC = 3.19 ± 0.27 - 12.24 ± 1.33 μM). Compound-9 showed promising inhibitory potential against urease, with an IC = 17.90 ± 0.30 μM, and α- glucosidase (IC = 3.19 ± 0.27 μM), both indicating minimum IC values. DISCUSSION: The enhanced activity of compounds bearing electron-withdrawing groups (F, NO2, Cl) supports their role in modulating enzyme inhibition. In silico molecular docking further confirmed strong binding affinities with the active sites of target enzymes, correlating well with the experimental results. CONCLUSION: The synthesized 1,3,4-oxadiazole derivatives demonstrate promising dual inhibitory activity against urease and α-glucosidase, suggesting their potential as lead compounds in the treatment of gastric infections and diabetes. This study contributes to the ongoing development of multifunctional therapeutic agents with improved efficacy and selectivity.
Recent Advances in the Biological Profiles of Fluorine-Containing Pyridine and its Derivatives: A Brief Overview.
Hussain A, Seher SS, Akhter S … +4 more , Shahzad K, Arfan M, Ko KC, Park SH
Med Chem · 2025 Sep · PMID 40947706 · Publisher ↗
Fluorine-containing pyridine derivatives have emerged as pivotal structures in modern drug discovery due to their unique physicochemical properties and diverse pharmacological activities. The incorporation of fluorine in...
Fluorine-containing pyridine derivatives have emerged as pivotal structures in modern drug discovery due to their unique physicochemical properties and diverse pharmacological activities. The incorporation of fluorine into pyridine-based scaffolds enhances drug potency, selectivity, metabolic stability, and Pharmacokinetics (PK) of these compounds, making them highly attractive for therapeutic development. These derivatives have been integrated into numerous Food and Drug Administration (FDA)-approved drugs, underscoring their importance in medicinal chemistry. This review systematically compiles recent advances in the pharmacological applications of fluorine-containing pyridine derivatives, focusing on their anticancer, antidiabetic, antioxidant, and anti-Alzheimer's activities. By exploring the Structure-Activity Relationship (SAR) and mechanisms of action, this review provides valuable insights for the design and development of novel biologically active compounds. This comprehensive analysis aims to inspire new directions in drug discovery and highlight the therapeutic potential of fluorine- containing pyridine derivatives.
Exploring Recent Advances in the Pharmacological Activities of Pyrazole Compounds: A Comprehensive Review.
Raut KG, Chabukswar AR, Waghmare PS … +3 more , Jagdale SC, Kachi OG, Pawar HR
Med Chem · 2026 · PMID 40947690 · Publisher ↗
Pyrazole-based compounds have gained considerable attention in recent years due to their diverse and potent pharmacological properties. This review provides an up-to-date examination of the therapeutic potential of vario...
Pyrazole-based compounds have gained considerable attention in recent years due to their diverse and potent pharmacological properties. This review provides an up-to-date examination of the therapeutic potential of various substituted pyrazole derivatives, highlighting their roles in combating diseases such as cancer, tuberculosis, fungal and viral infections, inflammation, and others. Unlike previous reviews, this article emphasises newly reported analogues with significant bioactivity and structure-activity relationships (SAR), which may pave the way for future drug development. The novelty of this work lies in its integrated perspective that bridges medicinal chemistry innovations with therapeutic relevance, providing researchers with a valuable resource for designing next-generation drug candidates based on the pyrazole scaffold.
Recent Advances in Synthetic Pathways and Therapeutic Potential of Acridine and Acridone Derivatives.
Dalvi KA, Pawar SS
Med Chem · 2026 · PMID 40947689 · Publisher ↗
Cancer, bacterial, parasitic, viral, and neurological diseases like Alzheimer's continue to pose serious health risks around the world. We need new therapeutic agents that are more targeted, effective, and safer. Because...
Cancer, bacterial, parasitic, viral, and neurological diseases like Alzheimer's continue to pose serious health risks around the world. We need new therapeutic agents that are more targeted, effective, and safer. Because of their wide range of biological actions, acridine and its derivatives have become increasingly popular among the numerous intriguing chemical classes. Over time, several synthetic analogs of these substances have shown great promise, exhibiting noteworthy antitumor properties (e.g., N-(2-(dimethylamino) ethyl) acridine-4-carboxamide (DACA) and triazole acridone (C-1305)), as well as strong antimicrobial (e.g., 4-amino-N-[amino(imino) methyl]-benzene sulphonamide), antiviral (e.g., derivatives of acridine sulphonamide), and anti- Alzheimer's (e.g., Citrusinine-I) properties. These substances have therapeutic potential, but side effects frequently prevent them from being used in clinical settings. This review discusses all the new developments in acridine and acridone derivatives since 2024. It focuses on how they are made and might be used in medicine. By shedding light on these innovations, the study aims to offer a fresh perspective on their role in shaping the future of medicinal chemistry and drug development. This work's main goal is to investigate and evaluate the most current progress in the synthesis as well as biological uses concerning derivatives of acridine along with acridone, especially those that have been published after 2024. The target of the study is to demonstrate the compounds' medicinal perspective by highlighting their antiviral, anticancer, antibacterial, and anti-Alzheimer effects. Furthermore, the research aims to tackle the difficulties related to their adverse effects, offering valuable perspectives for the creation of safer and more efficient medications in the field of medicinal chemistry in the future.
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