Shaaban Saad, Althikrallah Hanan A, Negm Amr, Abo Elmaaty Ayman, Al-Karmalawy Ahmed A
Department of Chemistry, College of Science, King Faisal University Al-Ahsa 31982 Saudi Arabia
Department of Chemistry, Faculty of Science, Mansoura University 35516 Mansoura Egypt.
RSC Adv. 2024 Jun 10;14(26):18576-18587. doi: 10.1039/d4ra02944e. eCollection 2024 Jun 6.
Organoselenium (OSe) agents hold promise for preventing cancer due to their potential ability to fight cancer development and protect cells from oxidative damage. Herein, OSe-based maleanilic and succinanilic acids were tested to estimate their antitumor activities against fifteen cancer cell lines. Besides, their potential safety and selectivity were further investigated against two normal cell lines, namely, human skin fibroblasts (HSF) and olfactory ensheathing cell line (OEC) using the growth inhibition percentage (GI%) assay. Moreover, the apoptotic potential of the superior anticancer candidates (8, 9, 10, and 11) was evaluated against P53, BAX, Caspase-3, Caspase-6, Caspase-8, Caspase-9, BCL-2, MMP2, and MMP9 apoptotic markers. Additionally, to enhance our understanding and predict the inhibitory potential of the examined compounds as potential anticancer agents, a thorough structure-activity relationship (SAR) analysis was conducted. On the other hand, molecular docking and ADMET studies were performed for the examined candidates as well. Overall, our findings point to significant anticancer activities of the organoselenium tethered amidic acids, suggesting their promising cytotoxic potential as effective anticancer drugs.
有机硒(OSe)制剂因其具有对抗癌症发展和保护细胞免受氧化损伤的潜在能力,有望用于预防癌症。在此,对基于OSe的马来酰苯胺酸和琥珀酰苯胺酸进行了测试,以评估它们对15种癌细胞系的抗肿瘤活性。此外,使用生长抑制率(GI%)测定法,进一步研究了它们对两种正常细胞系,即人皮肤成纤维细胞(HSF)和嗅鞘细胞系(OEC)的潜在安全性和选择性。此外,针对P53、BAX、半胱天冬酶-3、半胱天冬酶-6、半胱天冬酶-8、半胱天冬酶-9、BCL-2、基质金属蛋白酶2和基质金属蛋白酶9凋亡标志物,评估了最佳抗癌候选物(8、9、10和11)的凋亡潜力。此外,为了加深我们的理解并预测所研究化合物作为潜在抗癌剂的抑制潜力,还进行了深入的构效关系(SAR)分析。另一方面,也对所研究的候选物进行了分子对接和ADMET研究。总体而言,我们的研究结果表明,有机硒连接的酰胺酸具有显著的抗癌活性,表明它们作为有效的抗癌药物具有可观的细胞毒性潜力。