Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 4; pp. 5360 - 5373
• Main Authors: da Silva, Marciane Maximo, Comin, Marina, Duarte, Thiago Santos, Foglio, Mary Ann, de Carvalho, João Ernesto, do Vieira, Maria Carmo, Formagio, Anelise Samara Nazari
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.03.2015; MDPI
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antiproliferative activity; Cancer; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Electronic mail systems; Gallic Acid - analogs & derivatives; Gallic Acid - chemistry; galloyl; HT29 Cells; Humans; hydrazide; Hydrazines - chemical synthesis; Hydrazines - chemistry; Hydrazines - pharmacology; in silico study; MCF-7 Cells; Metabolism; Molecular Structure; oxadiazole; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Brazil
• ISSN: 1420-3049; 1420-3049
• 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.