Molecular Surface Features in Modeling the HIV-1 RT Inhibitory Activity of 2-(2,6-Disubstituted phenyl)-3-(substituted pyrimidin-2-yl)-thiazolidin-4-ones

The human immunodeficiency virus-1 reverse transcriptase inhibitory activity of 2-(2,6-disubstituted phenyl)-3-(substituted pyrimidin-2-yl)-thiazolidin-4-ones have been analyzed using combinatorial protocol in multiple linear regression (CP-MLR) with several electronic and molecular surface area features of the compounds obtained from Molecular Operating Environment (MOE) software. The study has indicated the role of different charged molecular surface areas in modeling the inhibitory activity of the compounds. The derived models collectively suggested that the compounds should be compact without bulky substitutions on its peripheries for better HIV-1 RT inhibitory activity. It also emphasized the necessity of hydrophobicity and compact structural features for their activity. The scope of the descriptors identified for these analogues have been verified by extending the dataset with different 2-(disubstituted phenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones. The joint analysis of extended dataset highlighted the information content of identified descriptors in modeling the HIV-1 RT inhibitory activity of the compounds.

Topological Descriptors in Modeling the HIV Inhibitory Activity of 2-Aryl-3-pyridyl-thiazolidin-4-ones

The HIV-1 RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones has been analyzed with different topological descriptors obtained from DRAGON software. Here, simple topological descriptors (TOPO), Galvez topological charge indices (GVZ) and 2D autocorrelation descriptors (2DAUTO) have been found to yield good predictive models for the activity of these compounds. The correlations obtained from the TOPO class descriptors suggest that less extended or compact saturated structural templates would be better for the activity. The participating GVZ class descriptors suggest that they have same degree of influence on the activity. In 2DAUTO class, the large participation of descriptors of lags seven and three indicate the association of activity information with the seven and three centered structural fragments of these compounds. The physicochemical weighting components of these descriptors suggest homogeneous influence of mass, volume, electronegativity and/ or polarizability on the activity.

Reductase inhibitory activity of some flavones: Topological descriptors in modeling the activity

In healthy people, glucose is metabolized through Embden-Meyerhoff pathway. In cases of diabetes mellitus, with the increased levels of glucose in insulin-insensitive tissues the Aldose Reductase (AR) in polyol pathway facilitates the conversion of glucose to sorbitol. In this cascade of events the accumulated sorbitol is attributed to be responsible for cataract, neuropathy and retinopathy in diabetic cases.1,2 Thus, the inhibition of AR in polyol pathway may prevent and lead to the cure of the complications arising out of the diabetes mellitus. In this background, Matsuda and coworkers3 studied the AR inhibitory activity of large number of flavones and related compounds from traditional antidiabetic remedies. Here, many of these compounds shared 2-Aryl-benzpyran-4-one as scaffold for different chemical groups surrounding this moiety. This offers scope to investigate the AR inhibitory activity of these compounds in relation to the functional group environment surrounding this core