Design, Synthesis, and Mechanistic Understanding of Thioxothiazole Scaffolds as Possible Apoptotic Inducers and CDK2 Inhibitors in Melanoma

Integrated design, synthesis, biological evaluation, and computational mechanistic insights of novel benzanilide derivatives as VEGFR-2 targeted anticancer agents

Findings identify compound 7e as a promising VEGFR-2-targeted anticancer lead with strong enzymatic inhibition, potent cytotoxicity, and a well-supported mechanistic profile integrating experimental and computational evidence.

Targeting CDK‐2 With Novel Indole‐Pyrazole Hybrids: Discovery of Potent Anticancer Agents Supported by Mechanistic and In Silico Studies

The current study devised and synthesized a novel class of pyrazole derivatives based on indole as possible inhibitors of cyclin‐dependent kinase‐2 (CDK‐2). 1H NMR, 13C NMR, NOESY, HMQC, and elemental analysis were used to confirm the structural integrity of the synthesized compounds. Promising CDK‐2 inhibitory activity was observed in biological assays, and numerous compounds exhibited sub‐micromolar IC50 values. Compound 5 d outperformed the reference inhibitor Roscovitine (IC50 = 0.716 µM) as the most potent inhibitor (IC50 = 0.536 µM), followed by compound 9 g (IC50 = 0.675 µM). SAR analysis showed that the observed activity was significantly influenced by the electronic nature of the added substituents as well as the orientation of the indole bond, with brominated derivatives exhibiting greater potency. The antiproliferative activity of the most potent compounds against the cancer cell lines HepG2, HCT‐116, and MCF‐7 was further assessed. In addition to having an enhanced selectivity index for normal MCF‐10A cells (SI = 8.00 vs. 4.96 for Roscovitine), compound 5 d had the greatest activity against MCF‐7 cells (IC50 = 6.78 µM), surpassing Roscovitine (IC50 = 8.11 µM). According to mechanistic investigations, compound 5 d significantly reduced the S‐phase population, markedly promoted apoptosis, and caused G1 and G2/M cell‐cycle arrest. Additionally, the consistent binding of compound 5 d within the ATP‐binding pocket of CDK‐2 was confirmed by molecular docking and molecular dynamics simulations, and attractive drug‐like and pharmacokinetic features, similar to those of Roscovitine, were demonstrated by in silico ADMET predictions. All of these results point to compound 5 d as a promising lead scaffold for developing potent CDK‐2‐targeted anticancer agents.

Design, synthesis, antiproliferative evaluation, and computational studies of novel quinoline–pyrazoline hybrids against breast and ovarian cancer cell lines

Among the synthesized compounds, PBc1 exhibited the greatest in vitro antiproliferative activity against both MDA-MB-231 and SK-OV-3 cell lines, suggesting that PBc1 is a promising compound for further biological and mechanistic investigation.

Design, Synthesis, In Vitro Cytotoxicity, and Molecular Docking of Novel 2-Thioxoimidazolidin-4-one Derivatives

Comprehensive Investigation of Benzimidazolium Derivatives Through Synthesis, Characterization, Cytotoxicity Activity, Immunocytochemistry, and ADME and Toxicity Analyses

The results indicated that the compounds possess high lipophilicity but show limited bioavailability due to low solubility and none of the compounds were predicted to cross the blood–brain barrier, which limits their potential for direct effects on the central nervous system.

A Novel Class of Pyrazole−1,2,3 Triazole Hybrids: Synthesis, Characterization, and Biological Evaluation

A new set of pyrazole‐1,2,3‐triazole conjugates ( 7a–o ) was synthesized via a three‐step protocol that included diazotization, cyclization, and a copper(I)‐catalyzed azide‐alkyne cycloaddition (“click” reaction). The alkyne intermediate was coupled with different aryl azides to obtain the final conjugates, which were carefully confirmed using spectroscopic techniques. The synthesized molecules were tested against MCF‐7 (breast cancer), PC‐3 (prostate cancer), and HeLa (cervical cancer) cell lines using the MTT assay. Some derivatives showed strong antiproliferative activity, especially against MCF‐7 cells. Antimicrobial screening demonstrated broad‐spectrum antibacterial and antifungal activity. Molecular docking studies with vascular endothelial growth factor receptor‐2 (VEGFR2) revealed favorable binding through hydrogen bonding and hydrophobic stacking, which aligned with the observed biological activity. In addition, in silico ADME‐T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions showed good pharmacokinetic properties and drug‐likeness, supporting their potential as lead molecules for further development. The synthetic method offers advantages such as simple operation, short reaction times, low toxicity, and a broad substrate range, highlighting its usefulness in designing bioactive heterocyclic scaffolds.