摘要：A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety, which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-75 A549, H460 and HT29) and PD-1/PD-L1 inhibitory activities. Moreover, several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293). The most promising compound llo showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45, 8.65, 6,57 and 8.13 gmol/L, respectively, and displayed weak cytotoxicity on the normal cell(HEK-293). Furthermore, screening of PD-1 /PD-L1 inhibitory activity revealed that compound llo could effectively inhibit the binding of PD-1/PD-L1, and the binding interactions of compound llo with PD-L1 protein were explored by molecular docking. All above evidences showed that compound llo might be worthy of further study as a valuable leading compound for the treatment of cancer.

摘要：随着人工智能技术的快速发展,小分子生成模型已成为药物发现领域的重要研究方向。该类模型,包括生成对抗网络(GANs)、变分自编码器(VAEs)和扩散模型等,已被证明在优化药物属性和生成复杂分子结构方面具有显著能力。本文综合分析了上述先进技术在药物发现过程中的应用,展示了其如何补充和改进传统药物设计方法。同时,提出了当前方法在数据质量、模型复杂性、计算成本及泛化能力等方面的挑战,并对未来的研究方向进行了展望。

摘要：随着中国医药产业逐渐从仿制药领域向创新药物领域转型,创新型药学人才成为医药企业健康稳定发展的迫切需求。药物化学作为药物设计和开发的基础学科,对培养创新型人才起着至关重要的作用。以培养创新型人才为导向,从教学内容、教学方式及教学实践三个方面对药物化学课程教学进行探索。