新型双噻唑衍生物的设计、合成及细胞毒活性评价：作为 Pim1 激酶的选择性抑制剂，及其构效关系研究。

Design, synthesis and cytotoxic evaluation of novel bis-thiazole derivatives as preferential Pim1 kinase inhibitors with and study.

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Modern University for Technology and Information (MTI) University, Cairo, Egypt.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2166936. doi: 10.1080/14756366.2023.2166936.

Bis-thiazole derivatives were synthesised conforming to the Pim1 pharmacophore model following Hantzsch condensation. Pim1 has a major role in regulating the G1/S phase which upon inhibition the cell cycle stops at its early stages. Derivatives and showed the best Pim1 IC 0.32 and 0.24 µM, respectively relative to staurosporine IC 0.36 µM. Further confirmation of and Pim1 inhibition was implemented by hindering the T47D cell cycle at G0/G1 and S phases where showed 66.5% cells accumulation at G0/G1 phase while demonstrated 26.5% cells accumulation at the S phase compared to 53.9% and 14.9% of a control group for both phases, respectively. Additional cytotoxic evaluation of and revealed strong antitumor activity with up-regulation of caspase-3 and down-regulation of VEGF and TNF immune expression with concomitant elevation of malondialdehyde levels in case of .

双噻唑衍生物是根据 Pim1 药效团模型，通过 Hantzsch 缩合反应合成的。Pim1 在调控 G1/S 期方面起着重要作用，当它被抑制时，细胞周期会在早期停止。与 staurosporine 的 IC0.36 μM 相比，衍生物和显示出最佳的 Pim1 IC0.32 和 0.24 μM。通过阻止 T47D 细胞周期进入 G0/G1 和 S 期，进一步证实了和对 Pim1 的抑制作用，其中显示 66.5%的细胞在 G0/G1 期积累，而显示 26.5%的细胞在 S 期积累，而对照组的两个阶段分别为 53.9%和 14.9%。和的进一步细胞毒性评估显示出强烈的抗肿瘤活性，同时上调 caspase-3，下调 VEGF 和 TNF 的免疫表达，并伴随着丙二醛水平的升高。