1. Studies on quinones. Part 47. Synthesis of novel phenylaminophenanthridinequinones as potential antitumor agents.
- Author
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Valderrama JA, Ibacache A, Rodriguez JA, Theoduloz C, and Benites J
- Subjects
- Antineoplastic Agents pharmacology, Cell Line, Tumor, Drug Screening Assays, Antitumor, Fibroblasts cytology, Humans, Inhibitory Concentration 50, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Molecular Structure, Quinones pharmacology, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology, Structure-Activity Relationship, Urinary Bladder Neoplasms drug therapy, Urinary Bladder Neoplasms pathology, Aniline Compounds chemistry, Antineoplastic Agents chemical synthesis, Cell Survival drug effects, Fibroblasts drug effects, Phenanthridines chemistry, Quinones chemical synthesis
- Abstract
In our search for potential anticancer agents, a series of 8- and 9-phenylamino-3,4-tetrahydro-phenanthridine-1,7,10(2H)-triones with substituent variations at 6-, 8- and 9-positions were prepared using a highly efficient sequence involving: a) solar photoacylation reactions of benzoquinone with arylaldehydes, b) one-pot procedure for the synthesis of 3,4-dihydrophenanthridine-1,7,10(2H)-trione intermediates from acylhydroquinones and c) highly regiocontrolled acid-induced amination reaction of phenanthridinequinones with phenylamines. The members of this series were in vitro evaluated using the MTT colorimetric method against one normal cell line and three human cancer cell lines. The SAR analysis indicates that the location of nitrogen substituents on the quinone nucleus, the presence of methyl, phenyl, furyl and thienyl groups at the 6-position and the aromatization of the angular cycloaliphatic ring of the phenylamino-3,4-tetrahydrophenanthridine-1,7,10(2H)-trione pharmacophore play key roles in the antitumor activity., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
- Published
- 2011
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