左氧氟沙星及其硫代衍生物的生物学评价:抗氧化活性、醛脱氢酶抑制作用以及对 A549 细胞系的细胞毒性

Hamza Abumansour, Osama H. Abusara, Wiam Khalil, Hassan Abul-Futouh, Ali I. M. Ibrahim, Mohammad K. Harb, Dina H. Abulebdah, Worood H. Ismail
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引用次数: 0

摘要

左氧氟沙星(LVX)是氟喹诺酮类抗生素中的一种,其抗癌作用也已在体外和体内进行过研究。在本研究中,我们使用 LVX 和新型 LVX 硫代衍生物(化合物 2 和 3)来评估它们的抗氧化活性、醛脱氢酶(ALDH)活性抑制和抗癌活性。此外,还研究了与多柔比星(DOX)的联合疗法。采用 2,2-二苯基-1-苦基肼(DPPH)测定法来确定抗氧化活性。NADH 荧光分光光度法用于测定 ALDH 的抑制作用。细胞存活率检测采用的是瑞香素染料法。分子操作环境软件用于分子对接实验。与抗坏血酸相比,DPPH 试验表明化合物 3 的抗氧化活性最高,约为 35% 的清除活性。与化合物 2 相比,化合物 3 在 200 µM 的浓度下对 ALDH 酶的活性有明显的抑制作用。在非小细胞肺癌(NSCLC)细胞株 A549 上,受试化合物的 IC50 值约为 100 µM。然而,通过与 DOX 联用,观察到细胞毒性明显增强,IC50 值明显降低;与 LVX 联用则产生了增效作用,联用指数值为 0.4。分子对接测试表明,化合物 3 与 ALDH 酶的结合能最小,亲和力强。考虑到化合物 3 的抗氧化活性、ALDH 活性抑制作用和分子对接结果,硫代 LVX 衍生物可与 DOX 联合用于 NSCLC 治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biological evaluation of levofloxacin and its thionated derivatives: antioxidant activity, aldehyde dehydrogenase enzyme inhibition, and cytotoxicity on A549 cell line

Biological evaluation of levofloxacin and its thionated derivatives: antioxidant activity, aldehyde dehydrogenase enzyme inhibition, and cytotoxicity on A549 cell line

Levofloxacin (LVX) is among the fluoroquinolones antibiotics that has also been studied in vitro and in vivo for its anticancer effects. In this study, we used LVX and novel LVX thionated derivatives; compounds 2 and 3, to evaluate their antioxidant activity, aldehyde dehydrogenase (ALDH) enzymes activity inhibition, and anticancer activity. Combination treatments with doxorubicin (DOX) were investigated as well. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the antioxidant activity. The NADH fluorescence spectrophotometric activity assay was used to determine the ALDH inhibitory effects. Resazurin dye method was applied for cell viability assays. Molecular Operating Environment software was used for the molecular docking experiments. Compared to ascorbic acid, DPPH assay showed that compound 3 had the highest antioxidant activity among the tested compounds with approximately 35% scavenging activity. On ALDH enzymes, compound 3 showed a significant ALDH activity inhibition compared to compound 2 at 200 µM. The IC50 values for the tested compounds were approximately 100 µM on A549 cell line, a non-small cell lung cancer (NSCLC) cell line. However, significant enhancement of cytotoxicity and reduction of IC50 values were observed by combining DOX and synergism was achieved with LVX with a combination index value of 0.4. The molecular docking test showed a minimum binding energy with a good affinity for compound 3 towards ALDH enzymes. Thionated LVX derivatives, may be repurposed for NSCLC therapy in combination with DOX, taking into account the antioxidant activity, ALDH activity inhibition, and the molecular docking results of compound 3.

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