Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

Abstract

On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.

Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation

“…Inspired by the aforementioned discoveries and in connection with our research work concerning the development of effective anti-breast cancer agents [15][16][17][18], we were endeavored to design novel indole derivatives that promisingly possess antiproliferative activity. Perceiving the significance of these facts and based on our growing research interest in marine natural products, we were persuaded to tackle this study to design and synthesize marine-inspired bis-indole derivatives that have potential in vitro antitumor activity against breast cancer.…”

One pot synthesis of 2‐substituted thiobenzoazoles containing α‐sulfenylated aromatic ketones under transition metal‐free conditions

“…Among them, 2-substituted thiobenzoazoles (especially the ones containing α-sulfenylated aromatic ketones) are especially important due to their biological and pharmaceutical activities [2]. They can be used as antibiotics, antiviral, antifungal, antidiabetic, and anti-cancer drugs [3][4][5]. Some representative examples are shown in Figure 1, such as compound a (antitumor agent), compound b (CCR3 selective antagonist), compound c (HIV-1 protease inhibitor), and compound d (MvfR/ PqsBC dual inhibitors) [6][7][8][9].…”

Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation

“…Taking the above into account and as a continuation of our endeavor towards developing novel anticancer agents [ 22 , 23 , 24 , 25 ], it was thought worthwhile to extend our examinations to probe certain pyridine-urea derivatives displaying potent anticancer activity. In this study, a new series of pyridine-ureas 8a – n ( Figure 2 ) was synthesized as potential anticancer agents.…”