Molecular modeling studies of some bioactive hexahydropyrimidine and acridone derivatives

Adeayo Olayinka Ajala, Tennessee State University


Seventeen hexahydropyrimidine and fifteen N-substituted acridone derivatives have been evaluated and modeled using CoMFA/CoMSIA and topomer CoMFA algorithms, respectively. On one hand, 3D-QSAR models of a series of fluorinated hexahydropyrimidine derivatives with cytotoxic activities have been developed using CoMFA and CoMSIA. These models provide a better understanding of the mechanism of action and structure-activity relationship of these compounds. By applying leave-one-out (LOO) cross validation study, the best predictive CoMFA model was achieved with 3 as the optimum number of components, which gave rise to a non-cross-validated r2 value of 0.978, and standard error of estimate of 0.059. Similarly, the best predictive CoMSIA model was derived with 4 as the number of components, r2 value of 0.999, and standard error of estimate, 0.011. On the other hand, topomer CoMFA models have been used to optimize the potency of 15 biologically active acridone derivatives selected from the literature. Their 3D chemical structures were sliced into three acyclic R groups, to produce a fragment that is present in each training set. The analysis was successful with 3 as the number of components that provided the highest q2 results: q2 is 0.56, which is the cross-validated coefficient for the specified number of components, giving rise to 0.37 standard error of estimate (q 2 stderr), and a conventional coefficient (r2) of 0.82, whose standard error of estimate is 0.24. These results provide structure-activity relationship (sar) among the compounds. The result of the Topomer CoMFA studies was used to design novel derivatives for future studies, while the models for hexahydropyrimidines will inspire the design and synthesis of novel compounds with enhanced potency and selectivity.

Subject Area

Molecular chemistry|Organic chemistry

Recommended Citation

Adeayo Olayinka Ajala, "Molecular modeling studies of some bioactive hexahydropyrimidine and acridone derivatives" (2012). ETD Collection for Tennessee State University. Paper AAI1519763.