Farooq Urva, Khan Faizullah, Mali Suraj N, Ghaffar Uzma, Hussain Javid, Khan Ajmal, Chaudhari Somdatta Y, Al-Shwaiman Hind A, Elgorban Abdallah M, Jawarkar Rahul D, Islam Waseem Ul, Al-Harrasi Ahmed, Shafiq Zahid
Institute of Chemical Sciences, Bahauddin Zakariya University Multan 60800 Pakistan
Department of Pharmacy, Abdul Wali Khan University Mardan KPK Pakistan.
RSC Adv. 2025 Apr 25;15(17):13284-13299. doi: 10.1039/d5ra02194d. eCollection 2025 Apr 22.
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and it is characterized by a high recurrence rate and the rapid development of drug resistance across various subtypes. Currently, there is no targeted therapy, which is specifically approved for the treatment of TNBC. In this study, we synthesized a series of -benzyl indole-3-carboxaldehyde-based hydrazones and subjected them to anticancer studies on MCF-10A and MDA-MB-231 breast cancer (BC) cell lines. Our results suggested that all the compounds exhibited significant anti-TNBC activity, especially on MDA-MB-231 cells. Compound 5b showed excellent activity on MDA-MB-231 (IC = 17.2 ± 0.4 nM). Furthermore, molecular docking analysis revealed that this compound had a higher binding affinity towards the target EGFR (epidermal growth factor receptor) with a docking score of -10.523 kcal mol. The molecular dynamics simulation of complex 5b:3W2S showed stable binding over a period of 100 ns. A detailed multi-linear regression (MLR) QSAR denoted the importance of key molecular descriptors, such as com_accminus_2A, fringNlipo6A, and spCplus_AbSA. These analyses indicate that the synthesized compounds deserve further studies for developing novel and more potent candidates against triple-negative breast cancer.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌形式之一，其特征是复发率高且各亚型均迅速产生耐药性。目前，尚无专门获批用于治疗TNBC的靶向疗法。在本研究中，我们合成了一系列基于苄基吲哚 - 3 - 甲醛的腙，并对MCF - 10A和MDA - MB - 231乳腺癌（BC）细胞系进行了抗癌研究。我们的结果表明，所有化合物均表现出显著的抗TNBC活性，尤其是对MDA - MB - 231细胞。化合物5b对MDA - MB - 231表现出优异的活性（IC = 17.2 ± 0.4 nM）。此外，分子对接分析表明，该化合物对靶点表皮生长因子受体（EGFR）具有更高的结合亲和力，对接分数为 - 10.523 kcal/mol。复合物5b:3W2S的分子动力学模拟显示在100 ns的时间段内结合稳定。详细的多线性回归（MLR）定量构效关系表明了关键分子描述符的重要性，如com_accminus_2A、fringNlipo6A和spCplus_AbSA。这些分析表明，所合成的化合物值得进一步研究，以开发针对三阴性乳腺癌的新型且更有效的候选药物。
