Future Med Chem [JOURNAL]
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200 papers
Discovery of novel 2,4-diarylaminopyrimidine derivatives as FAK inhibitors with potent anti-cancer potency.
Lv YZ, Song J, Zhang SY … +2 more , Xu Y, Xi SM
Future Med Chem · 2026 Apr · PMID 41934374 · Publisher ↗
AIM: To evaluate novel 2,4-diarylaminopyrimidine derivatives as FAK inhibitors for cancer therapy and investigate their antitumor activity and mechanism of action. MATERIALS AND METHODS: A series of derivatives (-) was d...
AIM: To evaluate novel 2,4-diarylaminopyrimidine derivatives as FAK inhibitors for cancer therapy and investigate their antitumor activity and mechanism of action. MATERIALS AND METHODS: A series of derivatives (-) was designed and synthesized by incorporating a hydrazone unit into the TAE-226 scaffold. Kinase assays were performed to assess FAK inhibitory potency and selectivity. Antiproliferative activity against human cancer cell lines was evaluated via MTT assay. Molecular docking and dynamics simulations analyzed the binding modes. Mechanistic studies, including Western blot, colony formation, migration, and flow cytometry assays, were conducted in KYSE30 and KYSE150 esophageal cancer cells. RESULTS: Compound potently inhibited FAK (IC = 67.22 nM) with significantly improved selectivity over Pyk2, ALK, and EGFR compared to TAE-226. D12 exhibited broad-spectrum antiproliferative activity across multiple cancer cell lines, with particular potency against esophageal KYSE30 (IC = 25.64 nM), gastric MGC-803 (IC = 33.72 nM), and ovarian PA-1 (IC = 28.77 nM) cells. Mechanistically, compound effectively suppressed FAK phosphorylation and downstream MAPK/ERK and AKT/mTOR signaling, leading to inhibition of colony formation, migration, cell cycle progression, and induction of apoptosis. CONCLUSION: Compound is a novel FAK inhibitor with improved selectivity and potent antitumor activity, representing a promising lead candidate for cancer therapy.
Synthesis of anticancer agents: molecular docking and ADME studies of new hydropyrimidine linked amide-pyridine derivatives.
Aarthi R, Looi CK, Mai CW … +1 more , Ramalingan C
Future Med Chem · 2026 May · PMID 41923459 · Full text
AIM: To develop novel hydropyrimidine linked amide-pyridine hybrids as anticancer agents. MATERIALS AND METHODS: An array of molecular hybrids has been synthesized and evaluated for their in vitro cytotoxicity against b...
AIM: To develop novel hydropyrimidine linked amide-pyridine hybrids as anticancer agents. MATERIALS AND METHODS: An array of molecular hybrids has been synthesized and evaluated for their in vitro cytotoxicity against breast (MCF-7, MDA-MB-231), pancreatic (AsPC-1, BxPC-3, SW1990), and normal cell lines (HEK-293, MRC-5, and MCF-10A). Further, in silico absorption, distribution, metabolism, and excretion (ADME), docking, molecular dynamics (MD) simulation and density functional theory (DFT) studies of potent hybrids were executed. RESULTS: Hybrids and showed enhanced activity against breast cancer cells with IC between 6.15 ± 0.39 and 41.82 ± 4.94 µM, while exhibited enhanced activity against both breast and pancreatic cancer cells with IC between 8.72 ± 0.64 and 36.24 ± 3.34 µM ( < 0.05, three independent biological replicates). Against breast cancer cells, displayed ~3-fold superior activity than 5-fluorouracil while against pancreatic cancer cells, it exhibited comparable to superior activity. Further, selectively targets cancer cells over normal cells considerably, binds well with thymidylate synthase (-8.8 kcal·mol) and forms stable complex as revealed from docking and MD simulations. ADME analysis proposes favorable features for good oral bioavailability. CONCLUSION: This study ascertains as a promising lead for further biological evaluation and structural optimization toward the development of potential anticancer agents against pancreatic and breast cancers.
Mechanosynthesis and computational studies of new imidazole-based selenium adducts as potential anticancer agents against human prostate and cervical cancer.
Abbas G, Bokhari TH, Iqbal MA … +2 more , Rehman S, Ali A
Future Med Chem · 2026 May · PMID 41914157 · Full text
AIMS: This study aimed to design and synthesize three new selenium adducts to evaluate their anticancer potential against human prostate cancer (PC3) and cervical cancer (HeLa) cell lines using MTT assays. MATERIALS AND...
AIMS: This study aimed to design and synthesize three new selenium adducts to evaluate their anticancer potential against human prostate cancer (PC3) and cervical cancer (HeLa) cell lines using MTT assays. MATERIALS AND METHODS: Imidazole-based selenium adducts, 1,3-dipropyl-1,3-dihydro-2H-imidazole-2-selenone (), 1-butyl-3-propyl-1,3-dihydro-2H-imidazole-2-selenone (), and 1,3-dihexyl-1,3-dihydro-2H-imidazole-2-selenone (), were prepared by using their corresponding symmetric and unsymmetrical -alkylated mononuclear imidazolium salts under solvent-free conditions through a mechanochemical approach instead of the conventional solution method. All synthesized compounds were characterized using elemental analysis, UV-visible, FT-IR, H-NMR, and C-NMR spectroscopic techniques. RESULTS AND CONCLUSIONS: The prepared compounds exhibited higher cytotoxicity against cancer cell lines than against normal cells. The results revealed that selenium adducts were more potent than their respective azolium salts. Among the test compounds, showed significant anticancer potential against both PC3 and HeLa cell lines with reasonably good IC values of 5.75 ± 0.21 µM and 7.86 ± 0.12 µM, respectively. Theoretical studies, comprising molecular docking and DFT analysis, reinforced the experimental results and suggest that selenium adducts can be used as new anticancer agents.
Design, synthesis, in silico, and biological evaluation of novel pyrazolopyrimidinone-based estrogen receptor inhibitors.
Hesham SA, Shahin MI, Ziko L … +4 more , Serya RAT, Farag NA, Abouzid K, Mowafy S
Future Med Chem · 2026 Apr · PMID 41891505 · Full text
AIMS: A series of pyrazolo pyrimidinone derivatives was designed and evaluated as estrogen inhibitors. MATERIALS AND METHODS: The newly synthesized compounds were tested for their antiproliferative activity on 60 NCI cel...
AIMS: A series of pyrazolo pyrimidinone derivatives was designed and evaluated as estrogen inhibitors. MATERIALS AND METHODS: The newly synthesized compounds were tested for their antiproliferative activity on 60 NCI cell lines. RESULTS: Compound emerged as the most potent antiproliferative agent, with a mean growth inhibition percentage (GI%) of 111.5%, followed by compounds . The NCI selected compounds and for five-dose assay, yielding GI50 values of 2.57-17.7 µM and 11.1-24.1 µM, respectively. Furthermore, flowcytometry analysis of the cell cycle on the MCF-7 cell line revealed that compounds induced cell cycle arrest at the G1 phase. Moreover, western blot was done for compounds and , showed two-fold greater potency than tamoxifen at 10 µM. The cytotoxicity of compounds 5a-d was evaluated against a normal human skin fibroblast cell line (HSF), which exhibited favorable safety profiles. A molecular docking study was conducted to investigate the binding mode and affinity of the new compounds to the estrogen alpha receptor (ERα). Finally, molecular dynamics simulations of compounds and were performed to support the stability of the protein-ligand complexes. CONCLUSION: Compounds and showed remarkable activity toward tumors which have higher estrogen expression.
Synthesis and biological profiling of novel quinoline-thiadiazole-thiazolone scaffolds as antimicrobial agents.
Modi HA, Pathak DV, Suradiya PD … +3 more , Chhag DB, Mahida AK, Jadav GL
Future Med Chem · 2026 May · PMID 41889132 · Full text
AIMS: The present study aimed to design and synthesize a series of quinoline-thiadiazole-thiazolone hybrid derivatives and evaluate their antibacterial and antifungal activities. MATERIALS AND METHODS: Ten derivatives ()...
AIMS: The present study aimed to design and synthesize a series of quinoline-thiadiazole-thiazolone hybrid derivatives and evaluate their antibacterial and antifungal activities. MATERIALS AND METHODS: Ten derivatives () were synthesized via an enaminone mediated condensation strategy and characterized using FT-IR, H NMR, C NMR and mass spectrometry. Antimicrobial activity was evaluated using the agar well diffusion method against Gram-positive bacteria (, ), Gram-negative bacteria (, ), and fungal strains (, , ). Streptomycin, ciprofloxacin, and nystatin were used as reference drugs. RESULTS: All synthesized compounds exhibited measurable antimicrobial activity with varying potency. Compounds showed the highest antibacterial activity, producing inhibition zones of approximately and , which are comparable to those of standard antibiotics (20-24 mm). Moderate antifungal activity was observed against and , with inhibition zones of , compared with nystatin (20-23 mm). Molecular docking studies supported these results by revealing favorable ligand-protein interactions for the most active derivatives. CONCLUSIONS: These findings demonstrate that quinoline-thiadiazole-thiazolone hybrids represent promising scaffolds for further optimization toward the development of novel antimicrobial agents.
Design, synthesis, and biological evaluation of disubstituted thiazolidinedione derivatives as pancreatic lipase inhibitors for the management of obesity.
Khan MS, Khator R, Yadav N … +3 more , A Jagtap U, Paul AT, Monga V
Future Med Chem · 2026 Apr · PMID 41885413 · Full text
AIM: Inspired by our previous research findings and to explore the effect of -3 and -5 substitution in relation to pancreatic lipase (PL) inhibitory activity, the present study aims at the design and synthesis of a serie...
AIM: Inspired by our previous research findings and to explore the effect of -3 and -5 substitution in relation to pancreatic lipase (PL) inhibitory activity, the present study aims at the design and synthesis of a series of disubstituted thiazolidinedione (TZD) derivatives and to evaluate their PL inhibitory activity. METHODS: A series of disubstituted TZD derivatives was synthesized by condensing various aldehydes on -5 and substituting 4-fluorobenzyl on -3 of TZD. The synthesized derivatives were screened for PL inhibitory activity. Further, kinetic study and various studies were also performed. RESULTS AND CONCLUSION: Compound displayed most potent inhibitory activity with IC value of 4.58 μM. Kinetic studies revealed competitive mode of inhibition for , , and with values 1.479, 1.827, and 1.939 μM; while their values were found to be 0.611, 0.958, and 0.939 μM, respectively. Docking studies confirmed good binding affinities of synthesized derivatives toward the active site of PL. Molecular dynamic simulation of revealed stability of the protein-ligand complex. Moreover, compound was predicted to have a satisfactory drug likeness profile. Compound can be used as a leading candidate for further structural optimization to identify more potent and efficacious PL inhibitors as anti-obesity agents.
Recent advances in the design and development of small molecules targeting the TLR4 signaling pathway.
Ishfaq M, Shahab M, Jiang G
Future Med Chem · 2026 May · PMID 41875215 · Full text
Toll-like receptor-4 (TLR4) is a key pattern recognition receptor that plays an essential role in initiating innate immune responses. However, dysregulated TLR4 signaling is associated with the progression of sepsis, neu...
Toll-like receptor-4 (TLR4) is a key pattern recognition receptor that plays an essential role in initiating innate immune responses. However, dysregulated TLR4 signaling is associated with the progression of sepsis, neurodegenerative disorders, cardiovascular and autoimmune diseases. Though the clinical progress of TLR4 inhibitors has been hindered by insufficient selectivity, poor pharmacokinetics and concerns of systemic immunosuppression, significant opportunities remain to design more selective and effective TLR4 modulators for diverse inflammatory and immune related diseases. In the past several years, diverse classes of inhibitors such as glycolipid mimetics, heterocyclic small molecules, natural product, peptides and compounds that downregulate receptor expression have shown promising biological activity in preclinical models of disease. These advancements have generated valuable insights into TLR4 recognition, signaling mechanisms and structure activity relationships. This review summarizes recent progress in the identification and design of TLR4 inhibitors, with emphasis on mechanistic characteristics, binding interactions, virtual screening methodologies and structural determinants that influence inhibitor performance. The collective evidence highlights the growing therapeutic potential of selective and broadly effective TLR4 modulators. As the field continues to advance, the further optimization of drug-like properties, in vivo efficacy and the integration of computational approaches will be essential to translate these promising candidates into clinically viable therapies.
Novel multitargeted Imidazo[1,2-]pyridine-1,3,4-oxadiazole hybrids: design, synthesis and biological evaluation as anti-Alzheimer's agents.
Shah D, Patel A, Patel A
Future Med Chem · 2026 May · PMID 41870450 · Full text
AIMS: To design, synthesize, and evaluate novel imidazo[1,2-]pyridine derivatives as dual acetylcholinesterase (AChE) and β-secretase (BACE1) inhibitors for potential Alzheimer's disease (AD) therapy. MATERIALS AND METHO...
AIMS: To design, synthesize, and evaluate novel imidazo[1,2-]pyridine derivatives as dual acetylcholinesterase (AChE) and β-secretase (BACE1) inhibitors for potential Alzheimer's disease (AD) therapy. MATERIALS AND METHODS: A series of imidazo[1,2-]pyridine derivatives () were synthesized via cyclization using various aryl and heteroaryl acids and characterized by MP, TLC, FTIR, MS, and H/C NMR spectroscopy. Molecular docking studies were performed against AChE (PDB ID: 4EY7) and BACE1 (PDB ID: 4ACU). Pharmacokinetic properties were predicted using pkCSM, and molecular dynamics simulations were conducted for the lead compound. inhibitory activities were determined by IC values. anti-AD activity was evaluated in male Sprague Dawley rats using biochemical assays and histological analysis. RESULTS: Compound showed the highest binding affinity toward both targets with stable protein-ligand interactions. It exhibited potent AChE inhibition (IC = 0.054 µM) and significant BACE1 inhibition (IC = 5.67 µM). studies demonstrated significant reversal of AD-associated biochemical and histopathological alterations at high dose. CONCLUSION: emerged as a promising dual AChE/BACE1 inhibitor and a potential lead candidate for further optimization in AD drug development.
Targets for bacterial resistance: recent advances in small-molecule FtsZ inhibitors.
Shao WB, Zhou X, Yang S … +1 more , Zhou Y
Future Med Chem · 2026 May · PMID 41870231 · Full text
ESKAPE pathogens (including , , , , , and ) represent a core challenge in the global antimicrobial resistance (AMR) crisis. Their multidrug resistance and high transmissibility pose severe clinical threats. However, the...
ESKAPE pathogens (including , , , , , and ) represent a core challenge in the global antimicrobial resistance (AMR) crisis. Their multidrug resistance and high transmissibility pose severe clinical threats. However, the pharmaceutical industry's current motivation for developing new drugs targeting these resistant bacteria remains insufficient. Consequently, creating antibiotics with novel mechanisms of action has become a strategic imperative for safeguarding global public health security. Therefore, targeting the bacterial cell division core protein filamentous heat-sensitive Z (FtsZ) has emerged as a key strategy to address the AMR crisis. FtsZ exhibits high conservation and prokaryotic specificity, making it an ideal target for developing novel antimicrobial agents. This paper systematically reviews the structural and functional mechanisms of FtsZ and summarizes research progress on inhibitors targeting its GTPase activity or assembly process - including natural products, synthetic small molecules, peptides, and nanomaterials - based on their sources and structural types. Consequently, drug development targeting FtsZ holds promise as a breakthrough solution for treating infections caused by drug-resistant bacteria such as ESKAPE pathogens.
Rational design and biological investigation of benzylidene-substituted pyrazolo[3,4-]pyridine derivatives as novel PIM-1 kinase inhibitors with anticancer potential.
Singh A, Maity S, Devi P … +2 more , Ali A, Asati V
Future Med Chem · 2026 Apr · PMID 41855502 · Full text
BACKGROUND: PIM-1 kinase is a significant oncogenic serine/threonine kinase that is implicated in various aspects of cancer cell proliferation, survival, and tumor progression. In this manuscript, a novel series of benzy...
BACKGROUND: PIM-1 kinase is a significant oncogenic serine/threonine kinase that is implicated in various aspects of cancer cell proliferation, survival, and tumor progression. In this manuscript, a novel series of benzylidene-substituted pyrazolo[3,4-]pyridine derivatives was designed and synthesized as potential PIM-1 kinase inhibitors with anticancer activity. METHODS: The novel derivatives were synthesized by a novel synthetic route involving a three-step synthetic method from 2-chloro-3-cyanopyridine to produce a total of ten derivatives 6A-6J. The structures of the novel derivatives were confirmed by Fourier Transform Infrared Spectroscopy (FT-IR), 1H and 13C Nuclear Magnetic Resonance Spectroscopy (NMR), and Mass Spectroscopy. The anticancer activity of the novel derivatives was assessed by evaluating their inhibitory activity against the MCF-7 human breast cancer cell line by a colorimetric MTT assay. The inhibitory activity of the novel derivatives against PIM-1 kinase was assessed by an enzyme-linked immunosorbent assay. The binding mode of the most active derivatives within the PIM-1 kinase active site was assessed by molecular docking studies. RESULTS: The results from this investigation revealed that some of the novel derivatives exhibited significant anticancer activity against the MCF-7 human breast cancer cell line. The most potent derivative 6H had an IC₅₀ value of 1.43 ± 0.18 μM, while compound 6D had an IC₅₀ value of 1.56 ± 0.30 μM compared to the standard drug doxorubicin. The inhibitory activity of the most active derivatives against PIM-1 kinase was concentration-dependent. The results from the molecular docking studies revealed that compound 6H had a favorable binding mode within the PIM-1 kinase active site by hydrogen bonding and hydrophobic interactions with some amino acid residues within the enzyme's active site. CONCLUSION: The results from this investigation revealed that benzylidene-substituted pyrazolo[3,4-]pyridine derivatives are potential anticancer agents that could be developed as potential anticancer drug candidates by inhibiting PIM-1 kinase activity.
A comprehensive review of indole hybrids as anti-bacterial and anti-fungal agents: synthetic protocols and SAR studies.
Bellapukonda SM, Anas Kt M, Mishra S … +5 more , Kodi R, Ghosh S, Korra LN, Nanduri S, Yaddanapudi VM
Future Med Chem · 2026 May · PMID 41854730 · Full text
Antimicrobial resistance, a consequence of the prevalent overuse and misuse of antibiotics, has become a serious global health concern. While extensive drug discovery efforts are constantly underway to combat this, the r...
Antimicrobial resistance, a consequence of the prevalent overuse and misuse of antibiotics, has become a serious global health concern. While extensive drug discovery efforts are constantly underway to combat this, the relentless emergence of resistant pathogens demands innovative strategies beyond traditional approaches to address this pervasive health crisis. Among promising strategies, such as drug repurposing and novel chemotype development, molecular hybridization, particularly involving the versatile indole heterocycle, stands out. Its inherent structural flexibility offers unique avenues for optimizing pharmacokinetics, boosting biological activity, and enabling potent bioisosteric modifications. This review consolidates and analyzes advances in indole-based derivatives reported between 2017 and 2025, specifically as antibacterial and antifungal agents. Beyond simply listing advances, we critically integrated chemical synthesis with structure-activity relationships (SAR) and their associated biological activity emerging from a broad spectrum of indole-based modifications. By rigorously detailing these insights, we specifically aim to guide and accelerate the rational design of novel indole-based molecules, providing a vital framework for developing the next generation of antimicrobials to overcome emerging resistance mechanisms.
Evaluation of new 5-benzylidenethiazolidin-2,4-dione derivatives linked to nitric oxide donor oxime moiety as VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative assessment and studies.
Abd El-Hameed AM, Ahmed NM, Fadaly WAA … +3 more , Zidan TH, El-Manawaty M, Magdy F
Future Med Chem · 2026 Apr · PMID 41837691 · Full text
AIM: Approaching VEGFR-2 blockers, two novel series of 5-benzylidenethiazolidine-2,4-dione and were synthesized. METHODS: Screening against and cancer cell lines. RESULTS: Derivatives and employed cytotoxicity agai...
AIM: Approaching VEGFR-2 blockers, two novel series of 5-benzylidenethiazolidine-2,4-dione and were synthesized. METHODS: Screening against and cancer cell lines. RESULTS: Derivatives and employed cytotoxicity against (22.75% to 55.30%) (Doxorubicin = 87.6%). Compound presented IC of 90.70 µM for (Doxorubicin = 32.36 µM). Concerning HCT-116 cell line, compounds 17d, 17e, and 17f haunted % inhibition (59.15% to 83.76%) (Doxorubicin = 96.8%). Besides, 17d, 17e, and 17f exhibited IC of 36.11, 54.50, and 67.22 µM, respectively (Doxorubicin = 21.27 µM). Also, compounds and disclosed safety outlines alongside normal cell IC (109.5 to 165 µM) (Doxorubicin = 38.51 µM). Compound arrested cell cycle at G2/M stage. Compounds released NO potentiating anti-cancer activity. , and inhibit VEGFR-2 (IC of 50.0 nM, 23.0 nM, and 111.0 nM, respectively) and sunitinib (84.0 nM). Western blot results displayed compound notable inhibition of the VEGFR-2/Akt/ERK axis. Docking studies revealed derivatives 17d-f docking score of -8.3 to -8.9 Kcal/Mol comparable to sunitinib and sorafenib. CONCLUSION: The present work flags the approach for advanced expansion of powerful nitric oxide donor offshoots as VEGFR-2 inhibitors.
Newly synthesized 2-cyclopentylidenehydrazinylthiazoles as potential therapeutic agents against peptic ulcer.
Sehrish, Salar U, Naz F … +4 more , Ishaq A, Naz F, Iqbal J, Khan KM
Future Med Chem · 2026 Apr · PMID 41816927 · Full text
BACKGROUND: Urease increases the stomach's pH by hydrolyzing urea and fostering the growth of Helicobacter pylori, linked to a variety of gastrointestinal issues, including peptic ulcers. Despite the availability of conv...
BACKGROUND: Urease increases the stomach's pH by hydrolyzing urea and fostering the growth of Helicobacter pylori, linked to a variety of gastrointestinal issues, including peptic ulcers. Despite the availability of conventional therapies, the development of safe and effective, nontoxic urease inhibitors with better pharmacological profiles remains an unmet need. METHODS: Novel 2-cyclopentylidenehydr azinyl thiazole derivatives were first time synthesized by first reacting cyclopentanone with thiosemicarbazide to afford thiosemicarbazone which then treated with different phenacyl bromides to afford products. RESULTS: All compounds exhibited outstanding urease inhibitory activity (IC50 = 0.14 to 6.39 µM) than the standard inhibitors thiourea and acetohydroxamic acid (AHA), with IC50 values of 19.43 and 41.3 µM, respectively. In fact, CH3 bearing compound (IC50 = 0.04 ± 0.008 µM) exhibited the highest inhibitory potential against urease. Structure-activity relationship (SAR) indicated that the inhibitory potential is strongly influenced by the electronic and steric factors. Furthermore, molecular docking experiments also revealed various interactions between the ligands (compounds) and the enzyme's active site. Detailed pharmacokinetics, drug-likeness, and absorption, distribution, metabolism, and excretion (ADME) properties were also assessed. CONCLUSION: This study demonstrates that these newly synthesized thiazole derivatives may serve as potential lead candidates for the discovery of antiulcer agents.
Wogonin-derived chemotype enables discovery of novel GLS1 inhibitors with potent antitumor activity.
Li X, Liang Y, Zhang X … +10 more , Wu Y, Wu T, Tian Y, Tang C, Qiu Z, Wu H, Bian J, Li Z, Xu X, Wang J
Future Med Chem · 2026 May · PMID 41816795 · Full text
AIMS: This study evaluates , a wogonin-derived glutaminase-1 (GLS1) inhibitor featuring a non- chemotype, designed to overcome the limitations of existing GLS1-targeted therapies. MATERIALS AND METHODS: Following targete...
AIMS: This study evaluates , a wogonin-derived glutaminase-1 (GLS1) inhibitor featuring a non- chemotype, designed to overcome the limitations of existing GLS1-targeted therapies. MATERIALS AND METHODS: Following targeted screening to identify the flavone-based inhibitor , we assessed its GLS1 inhibitory potency and antiproliferative effects in A549 and HCT116 cells. therapeutic efficacy was evaluated using an A549 xenograft model, alongside mechanistic studies to determine its impact on oncogenic signaling. RESULTS: effectively inhibited GLS1 (IC = 15.17 μM) and demonstrated potent antiproliferative activity in A549 and HCT116 cells. In A549 xenografts, achieved 50.3% tumor growth inhibition at 10 mg/kg, outperforming (21.6%) under identical conditions. Mechanistically, attenuated glutamine metabolism while concurrently suppressing signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) signaling, leading to G1 phase cell cycle arrest and induction of autophagy. CONCLUSIONS: The findings establish as a promising flavone-based, non- lead for GLS1 inhibition, exhibiting multi-pathway antitumor activity both and . This work provides a tractable lead compound for the development of next-generation GLS1 therapeutics.
Synthesis, characterization & molecular docking studies of rationally designed azobenzene-Derived 5-oxoimidazoline derivatives as potent antimicrobial agents.
Sharma V, Nain S
Future Med Chem · 2026 Mar · PMID 41814888 · Publisher ↗
AIM: The study aimed to design the series of azobenzene-induced 5-oxoimidazoline moiety, represents as a promising structural framework for the development of a new class of antimicrobial agents, supported by molecular d...
AIM: The study aimed to design the series of azobenzene-induced 5-oxoimidazoline moiety, represents as a promising structural framework for the development of a new class of antimicrobial agents, supported by molecular docking studies. MATERIALS & METHODS: Two series of compounds (10 in each series) were synthesized through a multistep procedure beginning with diazotization of 2-nitroaniline, followed by coupling with methyl paraben to yield azobenzene compound , which were subsequently refluxed with hydrazine hydrate to afford the hydrazide intermediate (11). Reaction of compound with substituted acetophenones and aldehydes produced schiff bases , which upon refluxing with amino acids (glycine and alanine) furnished the desired final compounds and . The compounds were screened for in-vitro antimicrobial activity & molecular docking studies were carried out to investigate ligand - protein interactions and to predict the most probable binding conformations. RESULTS: Compounds (MIC = 0.55 & 0.45 µg/ml, ΔG = -6.093), (MIC = 0.38 µg/ml, ΔG = -5.928), (MIC = 0.40 µg/ml, ΔG = -6.084) showed best anti-fungal activity displaying best docking score (PDB ID: 3LD6). The most active anti-bacterial compounds included (MIC = 0.70 & 0.88 µg/ml, ΔG = -5.832), (MIC = 0.54, 0.72& 0.39 µg/ml, ΔG = -5.755 & -5.845), (MIC = 0.34, 0.75& 0.55 µg/ml, ΔG = -5.683 &-5.894), (MIC = 0.65& 0.44 µg/ml, ΔG = -5.573) with best docking score (PDB ID: 2XCT & 6M1S). CONCLUSION: Compounds , , , & emerged as the most promising antimicrobial candidates, establishing them as potential lead molecules for further optimization and drug development.
Synthesis of acyl hydrazide derivatives of α-naphthalene acetic acid as COX-2 inhibitors: evaluation, molecular docking and DFT studies.
Bibi A, Alam A, Fareed G … +7 more , Ayaz M, Shah TA, Naz S, Qayum A, Ali Shah SA, Ali M, Ahmad M
Future Med Chem · 2026 Apr · PMID 41808456 · Full text
AIMS: Cyclooxygenase-2 (COX-2) is a key enzyme in pain perception and inflammatory cascade that make it an attractive target to develop safer anti-inflammatory agents. METHOD: In pursuit of potential anti-inflammatory ag...
AIMS: Cyclooxygenase-2 (COX-2) is a key enzyme in pain perception and inflammatory cascade that make it an attractive target to develop safer anti-inflammatory agents. METHOD: In pursuit of potential anti-inflammatory agents, a new series based on α-naphthalene acetic acid has been synthesized through multi step reactions process. H-NMR and C-NMR spectroscopic techniques were used to confirm the structures of these derivatives. RESULTS: These compounds have been assessed for their COX-2 inhibitory activity, among them, compounds exhibited excellent activity with IC value ranging from (IC = 0.36 ± 0.22 µM) to (IC = 0.43 ± 0.60 µM), while compounds showed significant activity. DISCUSSION: The molecular docking and density functional theory (DFT) analyses exposed that hydrazide derivatives based on α-naphthylene acetic acid displayed strong binding affinity for COX-2. Compound revealed the highest binding energy of -9.771 kJ mol and the lowest IC (0.43 µM) over π-π interactions and multiple hydrogen bonds. DFT study exposed that compound influenced the highest softening and the smallest HOMO-LUMO energy gap, representing improved reactivity. CONCLUSION: In general, the computational as well as experimental consequences specify that compound 13 is a potent COX-2 inhibitor.
Overview of recent strategic advances in antiviral covalent inhibitors.
Wang B, Wang S, Zhang J … +2 more , Kim M, Zhan P
Future Med Chem · 2026 May · PMID 41804708 · Full text
Targeted covalent inhibitors (TCIs) have emerged as a promising antiviral modality, functioning through irreversible or reversible modification of conserved nucleophilic residues within essential viral proteins. These ag...
Targeted covalent inhibitors (TCIs) have emerged as a promising antiviral modality, functioning through irreversible or reversible modification of conserved nucleophilic residues within essential viral proteins. These agents are increasingly recognized in antiviral drug discovery due to their potential to achieve enhanced target engagement and prolonged pharmacological effects when appropriately designed, thereby addressing limitations of traditional inhibitors such as rapid resistance development and suboptimal efficacy arising from insufficient binding durability. This review summarizes strategic frameworks for antiviral covalent inhibitor development, highlighting seminal and field-defining reports as well as recent advances. It provides a systematic overview of progress in high-throughput screening, mechanistic studies, and the integration of computational chemistry with artificial intelligence, thereby offering insights into the rational design and discovery of next-generation covalent antivirals.
Correction.
Future Med Chem · 2026 Jul · PMID 41782292 · Publisher ↗
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The future of hyperuricemia management: integrating recombinant uricase and mRNA therapeutics.
Chawla PA
Future Med Chem · 2026 Mar · PMID 41778519 · Publisher ↗
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Structural insights of ATP synthase and recent updates on molecular recognition of ATP synthase inhibitors: a review.
Patel E, Patel B
Future Med Chem · 2026 Apr · PMID 41773039 · Full text
In , the FFo-ATP synthase enzyme comprises five polypeptide chains (Chain and three subunits (Subunit , , and ), respectively. ATP is fundamental for the survival and growth of . In tuberculosis, this enzyme survives in...
In , the FFo-ATP synthase enzyme comprises five polypeptide chains (Chain and three subunits (Subunit , , and ), respectively. ATP is fundamental for the survival and growth of . In tuberculosis, this enzyme survives in harsh conditions like hypoxia, fluctuations in pH, and low nutrition in the host, further coercing it to enter the dormant state. Depletion of ATP stopgap the strains strenuous to survive. The discovery of Bedaquiline in 2012 has validated ATP synthase as a substantial target to combat resistance developed in strains. Recent research work done against ATP synthase provides a platform for a better understanding of structural features of chemical compounds and targeting unique epitopes of the ATP synthase enzyme in designing novel therapeutics against tuberculosis. This article summarizes the structural organizations as well as the solitary epitopes present in -ATP synthase. It also highlights its distinguished features from similar enzymes present in eukaryotes, fungi, and other bacterial species. Additionally, the present work reviews recent updates on various heterocyclic active chemical compounds designed as ATP synthase inhibitors for the treatment of tuberculosis till 2025.
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