da Silva Marciane Maximo, Comin Marina, Duarte Thiago Santos, Foglio Mary Ann, de Carvalho João Ernesto, do Vieira Maria Carmo, Formagio Anelise Samara Nazari
Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil.
Faculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil.
Molecules. 2015 Mar 25;20(4):5360-73. doi: 10.3390/molecules20045360.
The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution, metabolism and excretion (ADME) in the human body using Lipinski's parameters, the topological polar surface area (TPSA) and percentage of absorption (%ABS). In general, the introduction of N'-(substituted)-arylidene galloyl hydrazides 4-8 showed a moderate antitumor activity, while the 2-methylthio- and 2-thioxo-1,3,4-oxadiazol-5-yl derivatives 9 and 10 led to increased inhibition of cancer cell proliferation. The precursor compound methyl gallate 2 and the intermediary galloyl hydrazide 3 showed greater antiproliferative activity with GI50 values < 5.54 µM against all human tumor cell lines tested. A higher inhibition effect against ovarian cancer (OVCAR-3) (GI50 = 0.05-5.98 µM) was also shown, with compounds 2, 3, 9 and 10 with GI50 ≤ 0.89 µM standing out in this respect. The in silico study revealed that the compounds showed good intestinal absorption.
本研究旨在研究一系列带有取代-1,3,4-恶二唑和碳酰肼部分的没食子酰衍生物对十种人类癌细胞系的体外抗增殖活性。还使用Lipinski参数、拓扑极性表面积（TPSA）和吸收百分比（%ABS）对这些化合物进行了人体吸收、分布、代谢和排泄（ADME）的计算机模拟研究。总体而言，N'-(取代)-亚苄基没食子酰肼4-8的引入显示出中等抗肿瘤活性，而2-甲硫基-和2-硫代-1,3,4-恶二唑-5-基衍生物9和10导致癌细胞增殖抑制增加。前体化合物没食子酸甲酯2和中间体没食子酰肼3对所有测试的人类肿瘤细胞系显示出更大的抗增殖活性，GI50值<5.54μM。对卵巢癌（OVCAR-3）（GI50 = 0.05-5.98μM）也显示出更高的抑制作用，在这方面，GI50≤0.89μM的化合物2、3、9和10表现突出。计算机模拟研究表明这些化合物具有良好的肠道吸收。
