左氧氟沙星(LVX)是氟喹诺酮类抗生素之一,也已在体外和体内研究了其抗癌作用。在这项研究中,我们使用LVX和新型LVX硫化衍生物;化合物2和3,以评估其抗氧化活性,醛脱氢酶(ALDH)酶活性抑制,和抗癌活性。还研究了与多柔比星(DOX)的联合治疗。2,2-二苯基-1-吡啶酰肼(DPPH)测定用于确定抗氧化活性。使用NADH荧光分光光度活性测定来确定ALDH抑制作用。将瑞天青染色方法用于细胞活力测定。分子对接实验采用分子操作环境软件。与抗坏血酸相比,DPPH分析显示,在测试的化合物中,化合物3具有最高的抗氧化活性,具有约35%的清除活性。关于ALDH酶,与化合物2相比,化合物3在200μM时显示出显著的ALDH活性抑制。在A549细胞系上,测试化合物的IC50值约为100µM,非小细胞肺癌(NSCLC)细胞系。然而,通过组合DOX观察到细胞毒性的显著增强和IC50值的降低,并且与组合指数值为0.4的LVX实现协同作用。分子对接测试显示最小结合能,化合物3对ALDH酶具有良好的亲和力。ThionatedLVX衍生物,可能与DOX联合用于NSCLC治疗,考虑到抗氧化活性,ALDH活性抑制,和化合物3的分子对接结果。
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.