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.

Keywords: Polycyclic aromatic hydrocarbons; aromatic amines; quantum-chemical calculations; mutagenic/carcinogenic metabolites; DNA covalent adducts; carbocations

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986708786848686

Affiliations: 1: Unidad de Matematica y Fisica, INFIQC, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, Cordoba 5000, Argentina.

Publication date: 2008-12-01

More about this publication?

• 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.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Borosky, Gabriela L.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers