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

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.

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

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

Synthesis of triazolopyridazine derivatives using iodobenzene diacetate and evaluation of their anticancer activity against MCF-7 breast cancer cells

This study reports an efficient synthesis of 6-(4-methoxyphenyl)-3-aryl-[1,2,4]triazolo[4,3-b]pyridazine derivatives via oxidative cyclization of the corresponding hydrazones using iodobenzene diacetate as a mild and metal-free oxidizing agent. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, FTIR, and mass spectrometry. Their in vitro anticancer activity was evaluated against the MCF-7 breast cancer cell line, where four compounds (7a, 7c, 7d, and 7f) exhibited notable cytotoxic effects. Molecular docking studies suggested favorable binding interactions of these compounds with several cancer-related targets, including human 17β-hydroxysteroid dehydrogenase, topoisomerase IIα, p73 tetramerization domain, Bcl2-xL, EGFR tyrosine kinase, and survivin. Docking of the complete compound series (7a-7j) further supported the observed activity trends. These findings indicate that triazolopyridazine derivatives represent promising scaffolds for further investigation as anticancer agents. IBD was used as an environment friendly reagent for the synthesis of 1,2,4-triazolo[4,3-b]pyridazines by oxidative cyclization of hydrazone derivatives. 1,2,4-Triazoles showed excellent anticancer activity against breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. The molecular docking studies were carried out with several enzymes associated with breast cancer to find the effective binding of the synthesized compounds.

Design, Molecular Docking, and Biological Evaluation of Imidazo[2,1-b]thiazole Derivatives

The research includes all stages of development, which include designing, synthesizing, molecular docking work, and testing anticancer properties of imidazo[2,1-b]thiazole compounds (5A–5E). The molecular docking studies showed that the complex formed between the two proteins displayed strong binding capacity to epidermal growth factor receptor and estrogen receptor alpha. The researchers used the MTT assay to test the cytotoxic activity of synthesized compounds against MCF-7 and MDA-MB-231 cell lines, which demonstrated that cell viability decreased with increasing concentration. The compound 5E showed the strongest cytotoxic properties among all tested compounds, while 5C displayed the second-highest activity level based on its lowest IC₅₀ value. The flow cytometric analysis demonstrated that compound 5E caused cells to undergo apoptosis while blocking their normal cell cycle progression, which resulted in an increased SubG1 population. The studies revealed that compound 5E served as the main lead candidate for development as an anticancer drug.

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

Mechanical investigations indicated that 4m triggered apoptosis in a dose-dependent manner and modified the transcriptomic profile of HepG2 cells, affecting crucial pathways such as chemical carcinogenesis-DNA adducts, steroid hormone biosynthesis, and cytochrome P450-mediated xenobiotic metabolism.