Sur une tentative d'unification des théaories quantiques de la cancèrisation par les polyacènes: I. Thèorie des règions M, L, et B

Abstract

ResumeBien que la rCgion M des polyactnes soit beaucoup moins rCactive que leur rigion K, les rCactivitCs de AbstractThis study is a unified approach to quantum theories of polyacen carcinogenesis. Part I discusses the M, L, and B regions theory. Although the M region of polyacens is much less reactive than is the K region, the chemical reactivity of these two regions parallels each other. Consequently, the K-L Pullman's theory may be reformulated by replacing the K region by the M region. The M-L regions theory improves all the quantum structure-carcinogenic activity relationships obtained previously in the K-L framework. Moreover, it would appear that in these correlations, the most important role is played by nonconcerted electrophilic reactions. We suggest that the M-L modified Pullman's theory and the Bay (B) region theory, proposed by Jerina et al., are related to different steps of the metabolic activation mechanism leading to ultimate carcinogen: the first step for the Pullman's theory and the carbocation step for the theory of the Bay region. We have termed the "M, L and B regions theory" as this unified approach to the problem of polyacens carcinogenesis.

Structure−Activity Relationship Studies of Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons Using Calculated Molecular Descriptors with Principal Component Analysis and Neural Network Methods

“…Our experimental data to define active and inactive compounds are from the Iball indices 10 and from the scale proposed by Cavaliere et al 19 The set of 81 PAH molecules, sequentially numbered (Figures 1 and 2; Tables 1 and 2), was divided into two groups: G1 and G2. Group G1, category 1, consists of 34 active molecules (1-10 in Figure 1, 33-56 in Figure 2).…”

Theoretical Approach to Identify Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons

“…1. These molecules were selected based on the fact that the experimental Iball index [11] is available for them. This index is defined as the percentage of skin cancer or papilloma-developing mice (skin painting experiments) divided by the average latent period in days for the affected animals multiplied by 100 [12].…”

Carcinogenic classification of polycyclic aromatic hydrocarbons through theoretical descriptors

“…The compounds were labeled sequentially, and for the structure–activity investigation were divided into two groups of activity following the approach proposed by Villemin et al 7 (active ( A ) and inactive ( I ) molecules). For the experimental data the Iball 5 indices were considered and the scale of activity proposed by Cavalieri et al 19. The A subset incorporates the compounds with experimental indices +++++, ++++, +++ (from extremely active to active according to Cavalieri 19) whereas the subset I is composed by the remaining compounds with experimental indices ++, +, ±, and – (from moderately active to inactive according to Cavalieri 19) 9, 11–13.…”

“…Other similar theories evolved to include what is called the bay region 1, and recent ones, using statistical analysis, neural networks, and intelligence methods have been proposed and tested, but none is totally consistent with all the available experimental data. Some of them work well for a specific subset of compounds but fail for the remaining 5–8.…”