Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt.
Photochemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
Mini Rev Med Chem. 2019;19(15):1255-1275. doi: 10.2174/1389557518666180330110828.
Objective & Methodology: New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency was elicited by the target candidates against the viability of HCT116 cell lines. It was higher than that obtained by the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 μM, IC50, 5-FU; 1.10 μM). Results: Cell cycle analysis and apoptosis activation revealed that compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, compound 20 activates the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models. Conclusion: Furthermore, there is a good agreement between the observed pIC50 and the predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent and broad spectrum antibacterial and antifungal potency that was equivalent to that revealed by Vibramycin and Ketoconazole (MIC; 125 μg/mL). Moreover, compounds 15a, 21c, investigated dual potent antimicrobial and anticancer activity.
合成了噻吩-五/六杂环的新型杂合体，并对其体外抗三种人癌细胞系（即 HCT116（人结直肠癌细胞）、PC-3（人前列腺腺癌）和 HepG2（人肝癌）细胞系）的增殖活性进行了评估。候选物对 HCT116 细胞系活力的抑制作用最强，比阳性对照 5-氟尿嘧啶（IC50 范围为 0.11-0.49 μM，IC50，5-FU；1.10 μM）获得的抑制作用更高。结果：细胞周期分析和凋亡激活表明，化合物 20 诱导 HCT116 细胞发生 G2/M 期阻滞和凋亡。此外，化合物 20 激活了 caspase-9 和 caspase-3，这一过程可能介导了 HCT116 细胞的凋亡。进行了定量构效关系研究，结果表明模型具有较高的预测能力 R2。结论：此外，观察到的 pIC50 与预测的 pIC50 值之间存在良好的一致性，此外，低 RMSD 和标准误差值表明模型的准确性。抗菌评估显示，其中一些化合物对测试的致病菌和真菌表现出显著的活性，其中化合物 7a、14、15a、21a 产生了最有效和广谱的抗菌和抗真菌活性，与 Vibramycin 和 Ketoconazole（MIC；125 μg/mL）相当。此外，化合物 15a、21c 表现出双重有效的抗菌和抗癌活性。
