Novel Hydrazone Derivative with 4-(4-Aminophenoxy)-N-methylpicolinamide Moiety: Spectroscopic, Molecular Dynamics, and Docking Studies for Potential Anticancer Activity

Design, Synthesis, Characterization and Evaluation of Anticancer Activity of Substituted-4-(Substitutedphenylhydrazon o)-3,4-Dihydroquinolin-2-(1H)-One

1-Butylindoline-2,3-dione derivatives as potent VEGFR-2 inhibitors: synthesis, mechanistic anticancer studies, and molecular dynamics simulations

A novel series of N-butyl isatin (indolin-2-one) derivatives was designed and synthesized as potential VEGFR-2-targeted anticancer agents, drawing inspiration from the oxindole-based inhibitor sunitinib. The synthesized compounds were assessed for antiproliferative activity against colorectal cancer cell lines (HT29 and HCT116) and for their inhibitory potential on VEGFR-2. Compound 6b exhibited the highest potency, demonstrating strong VEGFR-2 inhibition comparable to that of sunitinib. Mechanistic investigations in HCT116 cells demonstrated that 6b induced G0/G1 cell cycle arrest and promoted apoptosis, which was associated with the upregulation of p53 and Bax, downregulation of Bcl-2, and suppression of Cyclin D1 and Cyclin E expression. Furthermore, 6b markedly decreased VEGF-A expression, supporting modulation of VEGF/VEGFR-2-associated signaling. Molecular docking studies involving VEGFR-2 (PDB ID: 4AGD) demonstrated favorable binding of compound 6b in the ATP-binding pocket, establishing essential interactions with essential residues. Docking validation was established through the successful redocking of sunitinib, yielding an RMSD of 0.44 Å. Additionally, 500 ns molecular dynamics simulations indicated stable backbone behavior, regulated ligand fluctuations, preserved structural compactness, and sustained hydrogen bonding within the 6b-VEGFR-2 complex. The findings collectively identify compound 6b as a promising lead candidate for further development as a VEGFR-2-targeted anticancer agent.

Design, one-pot synthesis, and structural characterization of novel 2-ureido-6-nitrobenzamide derivatives as MTDLs targeting HDAC8/epigenetic-kinase networks.

Modulating intersecting pathological pathways via multi-target directed ligands (MTDLs) is an active frontier in drug discovery. Herein, we report the design, one-pot synthesis, and characterization of a novel series of functionalized 2-ureido-6-nitrobenzamide derivatives 4-8 in 72-82% yields. Sequential nitration and imidization of phthalic anhydride 1, followed by sulfonylation, afforded the N-cyclic imide 2 and its sulfonyl ester building block 3. Aminolysis of 3 using various amines and hydrazines furnished target compounds 4-8 via a base-catalyzed Lossen rearrangement/addition-nucleophile ring-opening (ANRO) cascade. The structures were characterized using NMR, FT-IR, and mass spectrometry. In silico SwissADME analysis predicted favorable drug-like profiles adhering to Lipinski's Rule of Five. To normalized binding free energies, multi-parameter optimization (MPO) workflow utilizing, AutoDock Vina converted raw docking energies (ΔGcalc) into calculated logarithmic inhibition constants (pKi,calc) across ten targets proteins. The validated and predicted heavy-atom poses closely matched reference structures, with RMSD values confirming docking reliability, while 2D interaction diagrams verified conserved of key contacts. Compound 6 emerged as a prioritized multi-target template, with a balanced predicted dual-target profile against HDAC8 and JNK1. Compound 7 was identified as a prioritized in silico multi-target hit against HDAC8 and PIM1. Structural modifications shifted other derivatives toward target-biased profiles, such as building block 3 against GSK-3β and compound 8 against JAK2. Overall, these tunable 2-ureido-6-nitrobenzamide scaffold serves as an in silico prioritization starting point for the rational design of dual-action therapeutics targeting complex oncology and neurodegenerative networks, requiring future in vitro and in vivo validation.

Molecular Docking and ADME Profiling of N-(Substituted-1,3-benzothiazol-2-yl)benzamide Derivatives as Potential Anticonvulsant Agents

The docking analysis suggest that selected N-(substituted-1,3-benzothiazol-2-yl)benzamide derivatives, particularly Cp1, Cp3, Cp7, Cp10, Cp12, Cp13, and Cp14 were identified as the most promising lead candidates, with significant potential for anticonvulsant activity.

Tetrazole–imidazole hybrid derivatives as potential EGFR tyrosine kinase inhibitors: design, synthesis and in silico evaluation with preliminary antiproliferative assessment

SYNTHESIS, MOLECULAR DOCKING, AND ANTICANCER ACTIVITY OF NOVEL COUMARIN DERIVATIVES

Coumarin scaffolds are attractive templates for anticancer drug discovery because they modulate multiple molecular targets, including receptor tyrosine kinases, apoptosis regulators, and topoisomerases. This study aimed to synthesize, characterize, and evaluate three novel coumarin derivatives: 3-(4-fluorophenyl)-7-hydroxycoumarin (C1), 3-(3,4-dimethoxyphenyl)-7-methoxycoumarin (C2), and 6-bromo-3-(4-chlorophenyl) coumarin (C3). The compounds were synthesized using modified Pechmann or Knoevenagel condensation routes, purified by column chromatography, and characterized by FTIR, UV–Vis, 1H/13C NMR, LC–MS/MS, HRMS, elemental analysis, melting point, and TLC. Molecular docking was performed against EGFR, VEGFR-2, PI3K, CDK2, Bcl-2, and Topoisomerase II using validated protein structures, while drug-likeness and ADMET properties were predicted using SwissADME, pkCSM, and ADMETlab. Anticancer activity was assessed by MTT assay against MCF-7, A549, HeLa, and HCT-116 cell lines. The compounds were obtained in 58–74% yields with confirmed structures. C1 demonstrated the strongest binding toward EGFR (−9.1 kcal/mol) and Bcl-2 (−8.0 kcal/mol), forming key interactions with Met793 and hydrophobic residues, and exhibited the highest cytotoxicity against MCF-7 (IC₅₀ = 6.8 ± 0.9 µM) and HCT-116 (IC₅₀ = 9.5 ± 1.1 µM). C2 preferentially targeted CDK2 and PI3K, whereas C3 showed favorable binding to Topoisomerase II and VEGFR-2 with selective activity against A549 cells (IC₅₀ = 8.9 ± 1.2 µM). ADMET analysis predicted favorable oral drug-likeness for C1 and C2 with acceptable pharmacokinetic profiles. Overall, C1 emerged as the most promising lead for further optimization as a multitarget anticancer agent, while C2 and C3 provide complementary scaffolds for future medicinal chemistry and mechanistic investigations.