Faculty of Chemistry, University of Bucharest, 050663 Bucharest, Romania.
"Stefan S Nicolau" Institute of Virology, Romanian Academy, 030304 Bucharest, Romania.
Molecules. 2020 Jul 21;25(14):3308. doi: 10.3390/molecules25143308.
Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti- effects) was proved by . Compounds , , and determined blocking of G1 phase. Compound proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound had the best antibacterial activity, being used as a disinfectant agent. Compounds , , and , seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.
以异烟肼和羧酸为前体，合成了 13 种新的 2-（4-取代苯氧甲基）苯甲酸的酰肼和 1,3,4-噁二唑，并通过适当的方法进行了表征。通过对 HCT-8 和 HT-29 细胞系的细胞凋亡、细胞周期阻滞和药物代谢基因表达等方面评估了它们的生物性能。采用微量 Alamar Blue 测定法对分枝杆菌的抗微生物活性进行了体外抗菌试验，采用改良的琼脂圆盘扩散技术对其他非结核细菌株进行了抗菌试验。化合物 、 、 和 表现出最佳的抗菌活性（抗效）。化合物 、 、 和 确定了 G1 期阻滞。化合物 被证明具有毒性，在 72 小时后诱导 54%的细胞凋亡，这可以通过 24 小时后 mRNA 半胱天冬酶 3 和 7 的表达增加来预测。化合物对药物代谢相关酶基因表达的影响表明，合成的化合物可以通过 NAT2 以外的途径代谢，从而避免异烟肼的不良反应。化合物 具有最佳的抗菌活性，可用作消毒剂。化合物 、 、 和 似乎具有抗肿瘤潜力。进一步研究这些化合物对细胞周期的作用机制可能会为它们的生物活性提供新的信息。
