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

Synthesis, characterization, docking and in vitro evaluation of new pyrazole-carboxylate derivatives as antibacterial, anticancer and anti-inflammatory agents

Pyrazoles and chalcones have been extensively studied over time due to their broad range of therapeutic potentials. In this study, a new series of pyrazole-carboxylate derivatives were synthesized, characterized, and evaluated for their antibacterial, anticancer and anti-inflammatory activities. Among the synthesized derivatives, compound 5a exhibited significant percentage inhibition in colony counting assay. Compound 5c demonstrated significant cytotoxic activity with an IC50 value of 9.91 µg mL−1, while also exhibiting lower cytotoxicity towards non-cancerous HEK-293T cells (IC50 = 36.31 µg mL−1), indicating favourable selectivity. Mechanistic studies, including DAPI staining and flow cytometric analysis, indicated that compounds 5c and 5f inhibited cancer cell growth predominantly by inducing apoptosis rather than cell cycle arrest. Anti-inflammatory activity was determined using protein denaturation assay where compound 5f demonstrated promising activity with an IC50 value of 59.37 ± 0.149 µg mL−1. Furthermore, molecular docking analysis further provided insights into the binding interactions of the derivatives and the targeted protein. In addition, drug-likeness evaluation using swissADME indicates that the compounds satisfied Lipinski's rule of five.

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

Evaluation of Anticancer and Anti‐Inflammatory Activities of some Thiazole Derivatives

In this study, 2‐(heteroaryl thio)‐ N ‐(4‐methylthiazol‐2‐yl)acetamide ( 3a–3i ) derivatives were synthesized, and the anticancer activity of the compounds were investigated on A549 lung cancer and C6 glioma cell lines. Their anti‐inflammatory activities were tested against COX‐1, COX‐2, and LOX enzymes. Compounds 3a and 3c showed high cytotoxic activity against the A549 cell line, while compounds 3b, 3c, and 3f exhibited selective cytotoxicity against C6. Compared to cisplatin, a strong antiproliferative activity was detected against the C6 cell line. Further studies of anticancer treatments revealed that compound 3c significantly induced apoptosis, caspase‐3 activation, and mitochondrial membrane polarization against the A549 cell line. Compound 3c inhibited COX‐1 by 98.11% and 3h by 90.47%, while showing no significant inhibition of COX‐2 or LOX. Compound 3c , a derivative containing 2‐thiazoline, which showed the most potential in terms of both anticancer and anti‐inflammatory activity among all compounds, was subjected to molecular docking studies on Caspase‐3 and COX‐1 enzymes. Compound 3c was found to interact with Ser205, Arg207, and Gly122 of caspase‐3 enzyme via hydrogen bonds, and similarly, due to its hydrophobic property in both caspase‐3 and COX‐1 enzymes, 3c interacts with the hydrophobic regions of amino acids.

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.

Synthesis and Evaluation of Novel Piperazine Hybrids as Promising Anticancer Agents

The results revealed that the synthesised derivative 3h has potential binding affinity hence blocking the activity, and the synthesised piperazine derivatives are identified as promising lead compounds for further anticancer optimization.

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

This study aimed to develop novel CDK2 inhibitors with potent antimelanoma activity. Accordingly, a series of 2‐thioxothiazolyl pyrazoles (2–11) was rationally designed through molecular hybridization and synthesized using efficient and straightforward synthetic procedures. The structures of the synthesized compounds were confirmed by IR, NMR, mass spectrometry, and elemental analyses. All compounds were evaluated by the NCI, USA, against the 60‐human cancer cell line panel at a single dose (10 µM). The preliminary screening revealed promising antiproliferative activity, particularly against melanoma cell lines, with compound 11 exhibiting the highest growth inhibition against LOX‐IMVI and MALME‐3 M cells (21.60% and 49.41%, respectively). Based on these results, compounds 2, 4, and 11 were further evaluated by the MTT assay. Compound 11 exhibited the greatest cytotoxicity, with IC 50 values of 3.82 and 2.52 µM against LOX‐IMVI and MALME‐3 M cells, respectively, superior to doxorubicin and 5‐fluorouracil, together with excellent selectivity (SI = 12.14 and 18.40). Moreover, compound 11 potently inhibited CDK2 (IC 50 = 1.07 µM), approaching the activity of roscovitine (IC 50 = 0.84 µM), and induced cell cycle arrest at G1‐phase, besides promoting intrinsic apoptosis (23‐ to 40‐fold) in MALME‐3 M cells. These findings identify compound 11 as a promising selective CDK2‐targeted lead for melanoma therapy.