Title:Identification and Validation of CCR5 Antagonists from Maraviroc Analogs by Pharmacophore Modelling and 3D-QSAR Studies
Volume: 9
Issue: 3
Author(s): Sapam Tuleshwori Devi, Anushree Dutta, Bhagath Kumar Palaka, Mohd Babu Khan, Kasi Viswanath and Ampasala Dinakara Rao
Affiliation:
Keywords:
Antagonists, CCR5 receptor, co-receptor, HIV, maraviroc pharmacophore modeling, QSAR.
Abstract: Finding specific inhibitors for the immunodeficiency syndrome caused by virus, HIV-1 or HIV-2 is still a
difficult task. HIV most commonly uses CCR5 and CXCR4 as a co-receptor along with CD4 to enter the target cells.
CCR5 plays a main role in the integration of the virus inside the host cells by the interaction of CCR5 with the gp120 of
the virus. Hence, CCR5 has been considered as a potential drug target in the field of HIV, and researchers are trying to
find inhibitors or antagonists that can be targeted against CCR5 which can act as an entry inhibitor. In our current study,
ligand-based pharmacopore modeling was done for 41 analogs of maraviroc which are substituents of 1- Amido-1-phenyl-
3-piperidynylbutanes. It results in the formulation of a five-point hypotheses pharmacophoric model AADPR.356. The
main factor contributing the model AADPR.356 consists of two hydrogen bond acceptor groups, one hydrogen bond
donor group, one positively charged group, and one aromatic ring group. Our developed model represents a statistically
significant model with r2 value of 0.6801 and q2 value of 0.6731. Predicting the activity of the test set molecules provides
a means for validating the QSAR model developed, and the activities predicted were in the range of the observed
experimental activity values. Hence, our model represents a robust and statistical significant form which can be used to
design better potential drugs that can target against CCR5 receptor.
