Quantum Chemical Studies on Ultimate Carcinogenic Metabolites from Polycyclic Aromatic Hydrocarbons
Author: Borosky, Gabriela L.
Source: Current Medicinal Chemistry, Volume 15, Number 28, December 2008 , pp. 2901-2920(20)
Publisher: Bentham Science Publishers
Abstract:Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants well known as mutagenic/carcinogenic agents. This review will discuss recent theoretical studies regarding the stability and reactivity of ultimate carcinogenic metabolites from PAHs, focusing on their diol epoxide and amine derivatives. Geometrical and electronic features will be analyzed in order to obtain structure-activity relationships. Charge delocalization modes (positive charge density distribution), substituent effects, and conformational aspects will be considered. Computed properties will be compared with the available biological activity data. Correlations between experimental mutagenic potencies reported in the literature and calculated reaction energies and electronic properties will be shown. Heteroaromatic compounds (aza-PAHs, thia-PAHs, and heteroaromatic amines) will also be examined. To model the important step of covalent adduct formation, calculation of the adducts resulting from bond formation between some of these electrophilic intermediates and nucleotide bases (guanine, cytosine) will be described.
Document Type: Research article
Publication date: 2008-12-01
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.