Synthesis, Antiproliferative Activity and Molecular Properties Predictions of Galloyl Derivatives

Molecules

Marciane Maximo da Silva³  Marina Comin¹  Thiago Santos Duarte¹  Mary Ann Foglio⁴  João Ernesto de Carvalho⁴  Maria do Carmo Vieira²  Anelise Samara Nazari Formagio² 

[1] Faculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, Rodovia Dourados—Itahum, Km 12, Dourados, 79.804-970 MS, Brazil; E-Mails:;Faculdade de Ciências Agrárias, Universidade Federal da Grande Dourados, Rodovia Dourados—Itahum, Km 12, Dourados, 79.804-970 MS, Brazil; E-Mail:;Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Rodovia Dourados—Itahum, Km 12, Dourados, 79.804-970 MS, Brazil; E-Mail:;Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, 6171, Campinas, 13083-970 SP, Brazil; E-Mails:

关键词: galloyl;    hydrazide;    oxadiazole;    antiproliferative activity;    in silico study;   

DOI  :  10.3390/molecules20045360

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.