Structural design and cytotoxic profiling of a novel 1,3,4-thiadiazole derivative targeting MCF-7 and HCT-116 cell lines: synthesis, cytotoxicity, and in silico study

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

Design, synthesis, in silico, in vitro and in vivo anticancer potential of sulphonamide- ethylamine-triazole-aryl in against triple negative breast cancer and Dalton lymphoma.

It is suggested that 4c exerts anticancer activity through ROS-mediated mitochondrial apoptosis and cell-cycle disruption, highlighting its promise as an oncotherapeutic candidate for TNBC and Dalton lymphoma.

Novel benzofuran-furan-pyrano[2,3-c]pyrazole hybrids as potential anticancer agents: design, synthesis, in silico profiling, and multi-mechanistic biological evaluation

It is demonstrated that benzofuran-furan-pyrano[2,3-c]pyrazole hybrids possess promising multifaceted in vitro anticancer activity by inhibiting cancer cell proliferation, migration, invasion, and clonogenicity while inducing ROS-mediated mitochondrial apoptosis, highlighting these hybrid scaffolds as attractive candidates for further anticancer drug development.

Design, synthesis and dual anticancer and antibacterial evaluation of novel 1,3,4-oxadiazole-2-thiol derivatives targeting EGFR and DNA Gyrase B: integrated docking, DFT and ADMET studies.

Novel 1,3,4-oxadiazole-2-thiol derivatives (8a-j) were synthesized via multistep reactions and characterized using IR, 1H NMR, and 13C NMR spectroscopy. The compounds were evaluated for dual anticancer and antibacterial activities through computational and experimental approaches. Molecular docking against EGFR (1M17) and DNA gyrase B (2XCT) revealed compound 8h as the most potent EGFR inhibitor (-7.528 kcal/mol), surpassing methotrexate (-7.448 kcal/mol), while compound 8c demonstrated superior DNA gyrase B binding (-7.263 kcal/mol), exceeding ciprofloxacin (-6.11 kcal/mol) by 19%. In vitro cytotoxicity against A549 human lung carcinoma cells identified compound 8c as the most active anticancer agent (IC50 = 14.59 ± 0.19 µg/mL), comparable to methotrexate (IC50 = 11.82 ± 1.22 µg/mL). Antibacterial screening against S. aureus, E. coli, and K. pneumoniae revealed compound 8d as the most effective broad-spectrum agent (MIC = 25 µg/mL across all strains), demonstrating 2-fold superior activity against S. aureus versus ciprofloxacin. Comprehensive DFT calculations on compound 8c elucidated frontier orbital energies (HOMO-LUMO gap: 4.7528 eV), global reactivity descriptors, optimized geometry, Mulliken charge distribution, and topological properties (MEP, RDG, ELF, LOL). ADMET profiling revealed favorable drug-likeness with 0-1 Lipinski violations, optimal lipophilicity (cLogP: 2.7-3.97), and good predicted oral absorption (57-64%). These findings establish 1,3,4-oxadiazole-2-thiol derivatives as promising dual-action therapeutic scaffolds.

Design, robust synthesis, and anti-liver cancer activity of 2-hydrazono-5-acetyl-[1,3,4]thiadiazole and N'-ethylideneethanethiohydrazide derivatives: In vitro, gene expression, DNA damage, and DNA fragmentation.

A novel series of 2-hydrazono-5-acetyl-[1,3,4]thiadiazole (10-15) and N'-ethylideneethanethiohydrazide (17-21) derivatives were designed and synthesized using robust methodology and tested as anticancer agents against a panel of cancer cell lines, including PC3 (prostate cell line), A549 (lung carcinoma), HepG2 (hepatocellular carcinoma cell line), HCT116 (human colon cancer cell line), and the normal human fibroblast cell line (BJ1). The findings identified compounds coded 10 and 11 as the most promising candidates, with IC₅₀ values of 47 ± 0.24 μM and 50.8 ± 0.41 μM, respectively. Compound 10 exhibited selective cytotoxicity toward HepG2 cells with a selectivity index of 3.19. In contrast, the selectivity index for compound 11 could not be determined because it produced a negative effect on the BJ1 cells at the highest tested concentration. Furthermore, the mechanism of action of the most active compounds against liver cancer was explored through gene expression, DNA damage, and DNA fragmentation. Expression levels of the anti-apoptotic gene BCL-2 increased significantly (1 ± 0.046) in negative samples of liver cancer cell lines relative to the treated cell lines (10: 0.62 ± 0.033, and 11: 0.68 ± 0.038). BCL-2 expression decreased significantly in HepG2 + 10 (62% of control), followed by HepG2 + 11 (68% of control), and reached the lowest levels in HepG2 + Doxo (42% of control). In contrast, DNA damage values increased significantly in treated liver cancer cell line samples exposed to 10 (27.80 ± 1.36) and 11 (25.60 ± 1.29), as well as to the Doxo drug (33.20 ± 1.43). DNA fragmentation rates also increased significantly in treated liver cancer cells treated with 10 (24.48 ± 1.02), 11 (23.08 ± 0.94), and Doxo (29.54 ± 1.25) compared with the negative control.

Novel benzofuran-1,3,4-thiadiazole aryl urea hybrids as dual VEGFR-2/BRAF inhibitors: anticancer activity, apoptosis induction, and molecular modeling studies.

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.