Abstract

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP STUDY ON THE CDK2/CDK9 INHIBITORY ACTIVITY OF N2, N4-DISUBSTITUTED PYRIMIDINE-2,4-DIAMINES

Meena Dinesh Kumar and Sharma Brij Kishore*

ABSTRACT

QSAR study has been carried out on the CDK2 and CDK9 inhibitory activity of N2,N4-disubstituted pyrimidine-2,4-diamines in 0D- to 2D-Dragon descriptors. The derived QSAR models have revealed that the variation (descriptor VAR), sum of topological distances between F atoms (Descriptor T(F..F)) and atomic van der Waals volumes weighted Geary autocorrelations of lag-6 (descriptor GATS6v) played a pivotal role in rationalization of CDK2 inhibition activity of titled compounds. A higher values of descriptors VAR and T(F..F), and a lower value of descriptor GATS6v, would be beneficiary to the CDK2 activity. For the CDK9 inhibitory activity a lower value of descriptor TIE (E-state topological parameter), BEHm7 (atomic masses weighted highest eigenvalue n.7 of Burden matrix) and absence of CH2RX type structural fragment in molecular structure (descriptor C-006) would be beneficial. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.

Keywords: QSAR; CDK2/CDK9 inhibitory activity; Combinatorial protocol in multiple linear regression (CP-MLR) analysis; Dragon descriptors; N2,N4-disubstituted pyrimidine-2,4-diamines.