title: Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives.
abstract: 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.
authors: Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil. marcianemaximo@hotmail.com.
authors: Marciane Maximo
authors: MM
authors: da Silva
authors: Faculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil. marina_comin@hotmail.com.
authors: Marina
authors: M
authors: Comin
authors: Faculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil. thiagosantos948@gmail.com.
authors: Thiago Santos
authors: TS
authors: Duarte
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, 6171, Campinas, 13083-970 SP, Brazil. foglioma@cpqba.unicamp.br.
authors: Mary Ann
authors: MA
authors: Foglio
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, 6171, Campinas, 13083-970 SP, Brazil. carvalho_je@yahoo.com.br.
authors: João Ernesto
authors: JE
authors: de Carvalho
authors: Faculdade de Ciências Agrárias, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil. mariavieira@ufgd.edu.br.
authors: Maria Carmo
authors: MC
authors: do Vieira
authors: Faculdade de Ciências Agrárias, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, 79.804-970 MS, Brazil. aneliseformagio@ufgd.edu.br.
authors: Anelise Samara Nazari
authors: AS
authors: Formagio
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines; D010069:Oxadiazoles; C052082:methyl gallate; D005707:Gallic Acid; C019289:carbohydrazide