Prostate Cancer (PCa) is the most frequently diagnosed cancer in men in their late '50s. PCa growth is mainly due to the activation of the androgen receptor by androgens. The treatment for PCa may involve surgery, hormonal therapy, and oral chemotherapeutic drugs. A structural based molecular docking approach revealed the findings of (E)-N'-((1-chloro-3,4-dihydronaphthalen-2-yl)methylene)benzohydrazide derivatives, where the possible binding modes of the compounds with protein (PDB ID: 3V49) are shown. The compounds (6a-k) were synthesized and characterized by using conventional methods. The compounds, 6g, 6j, and 6k were reconfirmed through single crystal X-ray diffraction (XRD). Further, the compounds (6a-k) and standard drug were evaluated against human prostate cancer cell lines, LNCaP and PC-3 and the non-cancerous cell line, 3T3. Among these compounds, 6g and 6j showed higher cytotoxicity, and 6g exhibited dose-dependent activity and reduced cell viability. The mechanism of action was observed through the induced apoptosis and was further confirmed by western blot and ELISA. Molecular dynamics simulation studies were carried out to calculate the interaction and the stability of the protein-ligand complex in motion. ADME properties were predicted for all the tested compounds. These findings may give vital information for further development.

中文翻译：

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(E)-N'-((1-氯-3,4-二氢萘-2-基)亚甲基)苯甲酰肼衍生物作为抗前列腺癌药物的设计、合成和生物学评价。


前列腺癌 (PCa) 是 50 多岁男性最常诊断出的癌症。 PCa的生长主要是由于雄激素激活雄激素受体。 PCa 的治疗可能包括手术、激素治疗和口服化疗药物。基于结构的分子对接方法揭示了 (E)-N'-((1-氯-3,4-二氢萘-2-基)亚甲基)苯甲酰肼衍生物的发现，其中化合物与蛋白质 (PDB) 的可能结合模式ID：3V49）如图所示。采用常规方法合成并表征了化合物(6a-k)。通过单晶X射线衍射(XRD)再次确认化合物6g、6j和6k。此外，针对人前列腺癌细胞系LNCaP和PC-3以及非癌细胞系3T3评估了化合物(6a-k)和标准药物。在这些化合物中，6g和6j表现出较高的细胞毒性，6g表现出剂量依赖性活性并降低细胞活力。通过诱导细胞凋亡观察其作用机制，并通过western blot和ELISA进一步证实。进行了分子动力学模拟研究，以计算蛋白质-配体复合物运动中的相互作用和稳定性。预测所有测试化合物的 ADME 特性。这些发现可能为进一步发展提供重要信息。