Design and synthesis of 1,2,4-oxadiazole-functionalized funtumine derivatives as potent anticancer agents

Design and Synthesis of 2,4-Thiazolidinedione-Based Derivatives as Potent EGFR-Targeting Anticancer Agents

Structural–activity relationship analysis revealed the importance of the TZD core, electron-rich aromatic moieties, and balanced lipophilicity for enhanced anticancer activity, identifying TZD hybrids as promising EGFR-targeted anticancer leads.

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

Design, synthesis, antitumor estimation, and molecular docking of new imidazothiazolediones as potential dual EGFR and IDO1 inhibitors and apoptosis stimulators.

A novel set of imidazo[2,1-b]thiazolediones 4a,b and 5a-d, with anticipated EGFR and IDO1 inhibition activities, was designed and prepared. These novel derivatives were evaluated in the NCI 60 cell line panel in which the superior compounds 5b and 5d were chosen for further evaluation of their five dose cytotoxicity toward the most sensitive cancer cells namely non-small cell lung cancer EKVX and HOP-92, breast HS 578 T, and normal WI-38 cells. The presence of a substituted benzylidene moiety at position-2 of the imidazothiazole scaffold in compounds 5a-d positively influences anticancer activity, with the phenylallylidene moiety at position-6 exhibiting superior cytotoxic effects compared to the 2-thienylidene moiety. Among the examined hybrids, 5d showed significant antiproliferative effect against HS 578 T tumor cell. To explore the underlying cell-death mechanisms, secondary biological evaluations were conducted, including cell-free EGFR and IDO1 enzymatic inhibition, apoptosis assay, and cell cycle analysis. In cell-free biochemical assays, the most active derivatives demonstrated a promising potential dual inhibitory profile against EGFR and IDO1, with compound 5d exhibiting sub-micromolar activity against both target enzymes, providing a plausible biochemical rationale for its potent cell killing. Furthermore, compound 5d induced cell cycle arrest at the G2/M phase and triggered apoptosis in HS 578 T cells, as supported by the up-regulation of Caspase-3 and Bax accompanied by the down-regulation of Bcl-2. In-silico ADMET profiling and molecular docking simulations further supported the favorable drug-like properties and binding modes of the key compounds within the target active sites. Overall, these findings highlight compound 5d as a promising lead candidate for further optimization and cellular mechanistic validation in anti-cancer drug discovery.

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.

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.

Investigation of the In Vitro and In Silico Anticancer Potential of Novel 4‐Arylthiazole‐Hydrazone Derivatives

ABSTRACT The anticancer efficacy of 4‐aryl‐2‐hydrazinothiazole derivatives, which combine a thiazole known for its wide range of medicinal applications and a hydrazide/hydrazone structure known for its unique biological properties, has been determined in numerous studies. In this study, novel 2‐[4‐[(2‐(4‐substituted thiazol‐2‐yl)hydrazono)methyl]phenoxy]acetic acid derivatives (2a–l) were synthesized and evaluated for their anticancer activity in MCF‐7 breast cancer, A549 lung cancer, and L929 normal cell lines using cytotoxicity, apoptosis, and caspase‐3 activation assays. The compounds were found to exhibit high cytotoxicity, particularly showing more selective and high‐potential antiproliferative activity on the MCF‐7 cell line. In apoptosis studies, compounds 2c, 2d, and 2h caused programmed cell death in MCF‐7 cells exceeding 24%, close to cisplatin. Among these compounds, the derivative 2c containing 4‐methoxyphenyl caused caspase‐3 activation at a level similar to cisplatin. To conduct in silico studies of the compounds, molecular docking studies with the (4QTX) caspase‐3 enzyme, molecular dynamics simulation for three compounds (2d, 2g and 2l), and Density Functional Theory (DFT) studies were performed. These studies have shown that the carboxylate groups in the compounds form strong and stable interactions with Arg64 and Arg207.