Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
University College of Pharmacy, University of the Punjab, Lahore, Pakistan.
Anticancer Agents Med Chem. 2020;20(13):1516-1529. doi: 10.2174/1871520620666200516145117.
Due to the pressing need and adverse effects associated with the available anti-cancer agents, an attempt was made to develop the new anti-cancer agents with better activity and lesser adverse effects.
Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken with the aim of improving anti-cancer agents' safety profile.
In the present study, quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic acid (M1) and 2-(4-chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by the reaction of aldehyde and pyruvic acid. The complete reaction was indicated by thin-layer chromatography. Newly synthesized M1and M3were tested for in silico and in vitro studies.
M1 and M3 were docked against selected targets. Both the test compounds showed good affinity against all targets except the p300\CBP-associated factor target as there was no H-bond formed by M1. IC50 values of M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity were 562 and 136.56ng/mL, respectively. In brine shrimp lethality assay, M1 and M3 showed IC50 value of 81.98 and 139.2ng/mL, respectively. IC50 values recorded for M1 and M3 in tumor inhibition activity were 129 and 219μg/mL, respectively. M1 and M3 exhibited concentration-dependent anti-cancer effects against human cell lines of hepatocellular carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and 43.62μg/mL, respectively. M1 and M3 utilized against HCT-116 cell lines possessed IC50 values of 62.5 and 15.3μg/mL. M1 and M3 also showed an anti-leishmanial effect with IC50 values of 336.64 and 530.142μg/mL, respectively.
From the results of pharmacological studies, we conclude that the newly synthesized compound showed enhanced anti-oxidant, anti-cancer and anti-leishmanial profile with good yield.
由于现有抗癌药物的迫切需求和不良反应，我们试图开发具有更好活性和更少不良反应的新型抗癌药物。
基于喹啉衍生物的化学修饰，进行了合成方法研究，旨在改善抗癌药物的安全性。
在本研究中，通过醛和丙酮酸的反应合成了喹啉衍生物 6-羟基-2-(4-甲氧基苯基)喹啉-4-羧酸（M1）和 2-(4-氯苯基)-6-羟基喹啉-4-羧酸（M3）。薄层色谱显示完全反应。对新合成的 M1 和 M3 进行了计算机模拟和体外研究。
M1 和 M3 对接对选定的靶标。两种测试化合物均显示出对所有靶标良好的亲和力，除了 p300\CBP 相关因子靶标外，因为 M1 没有形成氢键。M1 和 M3 对 1,1-二苯基-2-苦基肼自由基清除活性的 IC50 值分别为 562 和 136.56ng/mL。在卤虫致死试验中，M1 和 M3 的 IC50 值分别为 81.98 和 139.2ng/mL。M1 和 M3 在肿瘤抑制活性中的 IC50 值分别为 129 和 219μg/mL。M1 和 M3 对人肝癌（HepG2）和结肠癌（HCT-116）细胞系表现出浓度依赖性的抗癌作用。对 HepG2 细胞，M1 和 M3 的 IC50 分别为 88.6 和 43.62μg/mL。M1 和 M3 对 HCT-116 细胞系的 IC50 值分别为 62.5 和 15.3μg/mL。M1 和 M3 还表现出抗利什曼原虫的作用，IC50 值分别为 336.64 和 530.142μg/mL。
从药理研究结果来看，我们得出结论，新合成的化合物具有良好的产率，表现出增强的抗氧化、抗癌和抗利什曼原虫作用。
