Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents
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Date
2010
Journal Title
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Volume Title
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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Abstract
Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells) and healthy fibroblasts (BALB/3T3) were assessed in vitro using the MTT reduction assay 48 h after drug exposure. SAR analysis of the aminonaphthoquinone series showed that insertion of a chlorine atom in the acceptor quinone nucleus and/or insertion of a methyl group at the nitrogen atom of the donor phenylamino group induced significant changes in cytotoxic activity. Quinones 7 and 9, which exhibited the highest selective indexes (5.73 and 6.29, respectively), were further characterized using the following assays: Colony formation, caspase-3 activity, and ATP content. The results showed that aminoquinone 7 strongly influenced ATP levels and impaired the proliferative capacity of T24 cells without activating caspase-3. (C) 2010 Elsevier Masson SAS. All rights reserved.
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Keywords
Antitumor agents, Cytotoxicity, Donor-acceptor systems, Quinones, Structure-activity relationships, SUBSTITUTED 1,4-NAPHTHOQUINONES, OXIDATIVE STRESS, VITAMIN-C, DERIVATIVES, APOPTOSIS, INHIBITION, HALLMARKS, PROTEINS, GROWTH, CANCER