Aug 2026· Journal of Computer-Aided Molecular Design· Vol 40· 0 citations· 31 references
Medicine
TL;DR
Two novel classes of hybrid quinazolin-2,4-diones 2–17, privileged with urea and/or carbamate moieties, as EGFR-TK inhibitors represent promising lead candidates for developing novel EGFR inhibitors for cancer treatment.
Combined computational and preliminary cell-based findings support compound 4i as a promising lead for further investigation of EGFR-targeted anticancer activity and biochemical EGFR kinase inhibition and target-engagement studies are required to determine the mechanism of action.
Sandip Badadhe, Vikas B. Gawali, C. Jangme et al.· Journal of the Iranian Chemi...· 0 citations
A novel series of benzofuran-based aryl urea derivatives incorporating a 1,3,4-thiadiazole linker were designed as dual VEGFR-2/BRAFWT inhibitors using sorafenib as a pharmacophoric template, with compound 7j emerging as the most active analogue.
Marwa I Serag, Mohamed R. Elnagar, Wafaa A. Ewes et al.· Bioorganic & Medicinal Chemi...· 0 citations
Compound 6b is identified as a promising lead candidate for further development as a VEGFR-2-targeted anticancer agent and stable backbone behavior, regulated ligand fluctuations, preserved structural compactness, and sustained hydrogen bonding within the 6b-VEGFR-2 complex are identified.
Mohamed El-Naggar, Hend I Abdelaal, Mohamed E Albakri et al.· RSC Advances· 0 citations
Abstract A series of novel sulfonamide derivatives of 6-(aminothiazole) flavones have been designed, synthesized and evaluated in MTT cell proliferation assay against three human cell lines, HeLa (Cervical carcinoma), Hep3B (Hepatocytic carcinoma) and MCF-7 (Breast carcinoma). All the compounds were analyzed by spectroscopic methods. Compound 10c IC50 of 21.93 µM is the good inhibitor of MCF-7 cell line. In sulfonamide series 10h with IC50 values 20.32 µM and 17.23 µM against HeLa and HeP3B cell lines is showing activity comparable with methotrexate. Docking results also have supported above observations by indicating that compounds are held in the active pocket by combination of various hydrogen and hydrophobic interactions. Graphical abstractChemical synthesis diagram of 2-Aminothiazole and Flavone hybridization, with IC50 values and molecular docking of compound 10b with proteins.The figure presents a detailed chemical synthesis diagram split into sections. At the top left, the structure of 2-Aminothiazole (pink) and Flavone (blue) are displayed, connected by an arrow indicating their hybridization. Below is a modified Flavone derivative marked with a sulfonamide group (in red). The central section features compound 10h's structure along with its HeLa IC50 = 20.32 µM and Hep3B IC50 = 17.23 µM values. Two molecular docking images illustrate compound 10b interacting with proteins 7L1X and 3QX3, labeled with amino acids and molecular interactions.
N. M. Thorat, Ashvini U. Chaudhari, A. P. Ingale et al.· Phosphorus Sulfur and Silico...· 0 citations
Cancer remains a leading cause of mortality worldwide, necessitating the development of new, selective, and potent therapeutic agents. In this study, a novel, metal-free, one-pot sequential synthetic approach was developed for the synthesis of carbazolyl-thiazolidinone (CTZD) derivatives via the reaction of N-octylcarbazole-3-carbaldehyde with variety of aromatic and aliphatic primary and secondary amines and thioglycolic acid. This strategy efficiently yielded a diverse range of CTZD derivatives (4a-p) in moderate to high yields (20-95%). The synthesized compounds were characterized by FTIR, NMR (1H, 13C, DEPT, APT), and HRMS. Their in vitro cytotoxicity was tested on human leukemia cell lines NB4, K562 and U937 using MTT assays, where four derivatives (4e, 4i, 4j, and 4o) exhibited potent, concentration-dependent antiproliferative activity over the tested concentration range (1.25-10 μM). As c-MYC is a key regulator of cell proliferation, qRT-PCR analysis demonstrated that these four derivatives significantly downregulated c-MYC mRNA expression, with compound 4j producing the greatest reduction, suggesting a potential association with modulation of the Wnt/β-catenin pathway. DNA fragmentation analysis showed no detectable late-stage apoptosis, indicating that the observed c-MYC downregulation and antiproliferative effects were not associated with late-stage apoptotic cell death. The ADME/T analysis of all compounds showed favorable pharmacokinetic profiles with prediction of good oral absorption (HIA >92%) and no hERG I liability. Molecular docking studies demonstrated strong binding affinities of these compounds to β-catenin protein (PDB ID: 7ZRB) with compound 4i showing strongest affinity with ΔG = -8.10 kcal/mol via H-bonds with Ser473, Asn430, Arg469 and His470 amino acid residues. The developed metal-free synthesis provided a sustainable route to bioactive carbazolyl-thiazolidinones, and derivatives 4e, 4i, 4j, 4o could be promising leads for targeting Wnt/β-catenin/c-MYC signaling in leukemia.
S. Shehzadi, Sana Naveed, D. Khan et al.· Bioorganic chemistry (Print)· 0 citations
A new series of pyrazolo[3,4-d]pyrimidine scaffolds, namely, 4a–l, were designed, synthesized, and tested for anti-inflammatory and anti-proliferative activities. Compounds 4f and 4g displayed advanced COX-2 selectivity (SI = 4.95 and 16.22) in comparison to celecoxib (SI = 7.61). In addition, all compounds were evaluated for their cytotoxic activity against three cancer cells using a reference drug (staurosporine). Compounds 4f and 4g showed the most potent anti-proliferative activity against MCF-7 (IC50 = 0.259 and 0.292 µM, respectively), MDA-MB-231 (IC50 = 0.258 and 0.327 µM, respectively), and Caco-2 (IC50 = 0.228 and 0.178 µM, respectively) cell lines and were more potent than staurosporine (IC50 = 0.401, 0.411, and 0.224 µM, respectively). Moreover, both derivatives were less toxic with comparable selectivity to the normal breast cell line (MCF-10) (SI values of 1.13–4.43) compared to staurosporine (SI values of 1.10–2.02). Further assessment of the CDK2 inhibitory activity of the most cytotoxic candidates 4f and 4g revealed their higher potency (IC50 = 0.324 and 0.215 µM, respectively) than that of the reference drug ribociclib (IC50 = 0.496 µM). Additionally, compound 4g revealed cell cycle arrest at the G2/M phase in Caco-2 cells, resulting in cell apoptosis. Furthermore, molecular docking and dynamics simulations revealed that derivatives 4f and 4g form stable and tighter complexes with the CDK2 kinase domain, as confirmed by their lower RMSD values, superior interaction stability, and stronger hinge and catalytic site binding. Finally, ADME profiling demonstrated that compound 4f satisfies all major drug-likeness criteria without any violations, while compound 4g fully adheres to the Veber's, Lipinski's, Egan's, and Ghose's drug-likeness guidelines. Consequently, these compounds represent promising starting candidates for the development of future CDK2 kinase and COX-2 inhibitors.
Sara Y. Ewieda, Laila Ziko, Ahmed Elshewy et al.· RSC Advances· 0 citations
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