Department for Toxicology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Laboratory of Pharm. Chemistry, School of Pharmacy, Aristotle, University of Thessaloniki, 54124 Thessaloniki, Greece.
Chem Biol Interact. 2018 Apr 25;286:119-131. doi: 10.1016/j.cbi.2018.03.013. Epub 2018 Mar 21.
The initial steps in preclinical drug developing research concern the synthesis of new compounds for specific therapeutic use which needs to be confirmed by in vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4-thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2-adamantylthiazol[3,2-b][1,2,4]triazol-6(5H)ones (5-8); and an ethylaminothiazole-based chalcone (9), were tested for antioxidant activity (AOA) by using three in vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive substances test). Compounds 1-4 and 9 in particular are newly synthesized compounds. Also, traditional antioxidants Vitamins E and C and α-lipoic acid (α-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E 2.99% and α-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; α-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated ∼50%; 3 and 8 displayed ∼38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, ∼100%, unlike α-LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox reaction principles between these assays dictate different AOA outcomes for a single compound. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbonyl functional domains and chelating ligand properties of the thiazolidinone derivatives correlated with AOA.
在临床前药物开发研究的初始步骤中， concern 是合成用于特定治疗用途的新化合物，这需要通过体外和体内测试来证实。 九个噻唑烷酮衍生物（编号为 1-9）分为以下几类：基于 1,3-噻唑的化合物（1 和 2）；基于 1,3,4-噻二唑的化合物（3 和 4）；取代的 5-亚苄基-2-金刚烷噻唑[3,2-b][1,2,4]三唑-6(5H)-酮（5-8）；和基于乙基氨基噻唑的查耳酮（9），通过三种体外测定法测试抗氧化活性（AOA）：DPPH（1,1-二苯基-2-苦基肼清除能力测试）；FRAP（铁还原抗氧化能力测试）；和 TBARS（硫代巴比妥酸反应物质测试）。 化合物 1-4 和 9 特别是新合成的化合物。 此外，还测试了传统抗氧化剂维生素 E 和 C 以及 α-硫辛酸（α-LA）。 DPPH 测试结果：维生素 C 94.35%，维生素 E 2.99%和 α-LA 1.57%；化合物：4 33.98%；2 18.73%；1 15.62%；5 6.59%；3 4.99%；6-9 几乎没有 AOA。 TBARS 测试结果（LPO 抑制的%）：维生素 C 62.32%；维生素 E 36.29%；α-LA 51.36%；化合物：1 62.11%；5 66.71%；9 60.93%；4、6 和 7 显示约 50%；3 和 8 显示约 38%；2 23.51%。 通过 FRAP 法，维生素 E 和 C 表现出相同的 AOA，约为 100%，而 α-LA（无 AOA）和测试化合物的 AOA（表示为维生素 C 的 AOA的分数）则为：2 和 4-75%；8、3 和 1-45%；5-7 和 9-27%。 这些测定中不同的氧化还原反应原理导致了单一化合物的不同 AOA 结果。 维生素 C 似乎是传统抗氧化剂中更好的抗氧化剂；而化合物 4 优于其他测试的噻唑烷酮衍生物。 维生素 C 似乎是传统抗氧化剂中更好的抗氧化剂；而化合物 4 优于其他测试的噻唑烷酮衍生物。 苯官能化亚苄基、氨基羰基官能域和噻唑烷酮衍生物的螯合配体性质与 AOA 相关。
