Alghamdi Maha Ali, Abdulbaqi Mustafa R, Alshaya Dalal Sulaiman, Alharthi Jawaher, Katouah Hanadi A, Elsaid Fahmy Gad, Fayad Eman, Abu Almaaty Ali H, Abdullah Alzahrani Abdullah Yahya, Beshay Botros Y
Department of Biotechnology, College of Sciences, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Al-Naji University Baghdad 10015 Iraq.
RSC Adv. 2025 Jun 3;15(23):18490-18500. doi: 10.1039/d5ra02384j. eCollection 2025 May 29.
Currently, the human health is facing numerous challenges, especially with regard to cancer. Therefore, new treatment options that specifically target tumor cells will inevitably improve the therapeutic toolkit for various cancers. In this regard, a sequence of acrylamide-PABA hybrids 4a-j was synthesized, and their formation was confirmed spectral and elemental analyses. The compounds were evaluated for their antiproliferative activity against MCF-7 (breast), HepG2 (liver) and a normal health breast cell line (MCF-10A). Among the series, acrylamide-PABA analog 4j with a furan group in the acrylamide moiety was the most potent anti-proliferative member with a notable IC value (IC = 1.83 μM) against MCF-7 cells. Compound 4j's anti-tubulin activity and apoptosis-promoting properties were the cause of its anti-proliferative inhibitory mechanism. Compound 4j promoted apoptosis in MCF-7 cells by raising the expression of apoptotic markers, such as p53, Bax, Bcl-2 and caspase 9, with respect to the untreated control. The molecular docking study of compound 4j revealed a nice fitting into the active site of tubulin.
目前，人类健康面临着诸多挑战，尤其是在癌症方面。因此，专门针对肿瘤细胞的新治疗方案将不可避免地改善各种癌症的治疗手段。在这方面，合成了一系列丙烯酰胺 - 对氨基苯甲酸杂化物4a - j，并通过光谱和元素分析证实了它们的形成。评估了这些化合物对MCF - 7（乳腺癌）、HepG2（肝癌）和正常健康乳腺细胞系（MCF - 10A）的抗增殖活性。在该系列中，丙烯酰胺部分带有呋喃基团的丙烯酰胺 - 对氨基苯甲酸类似物4j是最有效的抗增殖成员，对MCF - 7细胞具有显著的IC值（IC = 1.83 μM）。化合物4j的抗微管蛋白活性和促凋亡特性是其抗增殖抑制机制的原因。相对于未处理的对照，化合物4j通过提高凋亡标志物如p53、Bax、Bcl - 2和caspase 9的表达来促进MCF - 7细胞凋亡。化合物4j的分子对接研究表明它能很好地契合微管蛋白的活性位点。
