QSAR FOR CARCINOGENICITY IN METHYL BENZ[a]ANTHRACENES AND BENZ[c]ACRIDINES USING π-ELECTRONIC DATA IN A SELF-CONSISTENT FIELD MO THEORY

Abstract

Quantitative structure-activity relationships were obtained for series of methyl benz[a]anthracene and benz[c]acridine molecules. Regression analysis was done on π-electronic indices associated with specified molecular regions of importance named “bay” (Q _AB ),“K” (Q _K ), “L”(QL), N-heteroatomic position (QN) and superdelocalizability index (SK associated with K-region) of these molecules to correlate with reported experimental carcinogenicity indices. The electronic indices calculated earlier for methyl benz[c]acridines by a self-consistent field molecular orbital theory named ‘two-parameter omega-technique’ are reported from unpublished data. ‘Two-parameter omega-technique’ used successfully for methyl derivatives earlier, was modified to incorporate the N-heteroatom present in benzacridines. Reported log (carcinogenicity indices) for a series of 14 methylbenz[a]anthracenes are found to be positively correlated with Q _AB having correlation coefficient (R = 0.65) which is increased to 0.82 by combining this correlation equation with that depending on QL which is negatively correlated (R = 0.7) with reported log (carcinogenicity indices). Highly significant positive correlations of QN (R = 0.92), Q _AB (R = 0.85) and SK (R = 0.90) and negative correlations of QL (R = 0.94) for a series of 9 methyl benz[c]acridines with reported cancer indices are obtained. Combining the negative correlation equation dependent on QL with the best positive correlation equation involving QN cannot improve the correlation coefficient, but still gives the best value of (R = 0.94) for methylbenz[c]acridines. The carcinogenicities of a series of methyl derivatives of benz[a]anthracene and benz[c]acridines are discussed in terms of the relationships with frontier electron density and superdelocalizability of specific regions of molecular periphery of these molecules. π-Electron density obtained by combination of electron-density of a low reactive L-region with a highly reactive region like bay-region, K-region or nitrogen-atom position of molecular periphery is found to be the best indicator of carcinogenicity in a series of methyl benz[a]anthracenes and benz[c]acridines.

Keywords:

• benz[a]anthracene
• benz[c]acridine
• prediction of carcinogenicity
• quantitative structure-activity relationship

Keya Dhar and Keya Roy is the one and the same person.

Notes

^a DMBA, 7,12-dimethylbenz[a]anthracene; 7-MBA,7-methylbenz[a]anthracene; BA,benz[a]anthracene (see Figure 1 for nomenclature).

^b ,

^c Data from Majumdar et al. (4, 8) except DMBA from Roy (7).

^d Data from Roy (7).

^e Data fromLewis et al. (3).

^a Excluding benzo-ring derivatives.

^b Including benzo-ring derivatives.

^{a a} Data from Roy (7).

^b 8-Me, 8-methylbenz[c]acridine; 10,11-dMe, 10,11-dimethylbenz[c]acridine.

^c C.I, cancer index that is the average of painting and injection technique. Data from (13).

^d C.A, carcinogenic activity data from Satoh et al. and Motohashi et al. (9, 14).