In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 7; p. 1060
• Main Authors: Escobedo-González, René, Vargas-Requena, Claudia Lucia, Moyers-Montoya, Edgar, Aceves-Hernández, Juan Manuel, Nicolás-Vázquez, María Inés, Miranda-Ruvalcaba, René
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-06-2017; MDPI
• Subjects: Apoptosis; Bioinformatics; Cancer; Cell Line, Tumor; Cell Survival - drug effects; chemioinformatics tools; Computational Biology - methods; Computer Simulation; Cytotoxicity; Docking; docking study; Humans; Hydrogen Bonding; indolylquinones; Metabolic pathways; Metabolism; Molecular Docking Simulation; Molecular Structure; Neoplasms - drug therapy; Neoplasms - metabolism; perezone; Pharmacology; Physicochemical properties; quantum chemistry calculations; Quantum Theory; Quinones; Quinones - chemistry; Quinones - pharmacology; Sesquiterpene quinone; Sesquiterpenes - chemistry; Signal Transduction - drug effects; chemioinformatics tools; apoptosis; cancer; docking study; indolylquinones; quantum chemistry calculations; perezone
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22071060

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC
value ranking,
indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.