April Journal-2009.p65 - Association of Biotechnology and Pharmacy
April Journal-2009.p65 - Association of Biotechnology and Pharmacy
April Journal-2009.p65 - Association of Biotechnology and Pharmacy
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Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong><br />
Vol. 3 (2) 149-154, <strong>April</strong> 2009. ISSN 0973-8916<br />
Prediction <strong>of</strong> HIV-1 Protease Inhibitory Activity <strong>of</strong> (4-Hydroxy-<br />
6-Phenyl-2-Oxo-2H-Pyran-3-yl) Thiomethanes: QSAR Study<br />
V. Ravich<strong>and</strong>ran a+ , Abhishek K. Jain a , V.K. Mourya b <strong>and</strong> R. K. Agrawal a *<br />
Department <strong>of</strong> Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (M.P.), India<br />
b<br />
Govt. College <strong>of</strong> <strong>Pharmacy</strong>, Osmanpura, Aurangabad, Maharashtra, India<br />
+Present Addres : Faculty <strong>of</strong> <strong>Pharmacy</strong>, AIMST University, Semeling - 08100, Kedah, Malaysia<br />
* For Correspondence - dragrawal2001@yahoo.co.in - phravi75@rediffmail.com<br />
Abstract<br />
In pursuit <strong>of</strong> better HIV-1 protease<br />
inhibitory agents, QSAR studies were performed<br />
on a series <strong>of</strong> (4-hydroxy-6-phenyl-2-oxo-2hpyran-3-yl)<br />
thiomethanes using WIN CAChe 6.1.<br />
Stepwise multiple linear regression analysis was<br />
performed to derive QSAR models which were<br />
further evaluated for statistical significance <strong>and</strong><br />
predictive power by internal <strong>and</strong> external<br />
validation. The best QSAR model was selected,<br />
having correlation coefficient (R) = 0.923 <strong>and</strong><br />
cross-validated squared correlation coefficient<br />
(q 2 ) = 0.743. The developed best QSAR model<br />
indicates that the hydrophobicity <strong>and</strong> ionization<br />
potential play an important role in the HIV-1<br />
protease inhibitory activities.<br />
Keywords: QSAR; HIV-1 protease inhibitory<br />
activity; multiple linear regressions;<br />
thiomethane.<br />
Introduction<br />
HIV- 1 (Human Immunodeficiency Virus<br />
Type-1) is the pathogenic retrovirus <strong>and</strong> causative<br />
agent <strong>of</strong> AIDS or AIDS- related complex (ARC)<br />
(1). When viral RNA is translated into a<br />
polypeptide sequence, it is assembled in a long<br />
polypeptide chain, which includes several<br />
individual proteins namely, reverse transcriptase,<br />
protease, integrase, etc. Before these enzymes<br />
become functional, they must be cut from the<br />
longer polypeptide chain.<br />
Acquired immune deficiency syndrome<br />
(AIDS) is a formidable p<strong>and</strong>emic that is still<br />
wreaking havoc world wide. The catastrophic<br />
potential <strong>of</strong> this virally caused disease may not<br />
have been fully realized. The causative moiety <strong>of</strong><br />
the disease is human immunodeficiency virus<br />
(HIV), which is a retrovirus <strong>of</strong> the lentivirus family<br />
(2). The three viral enzymes; reverse<br />
transcriptase, protease <strong>and</strong> integrase encoded by<br />
the group specific antigen <strong>and</strong> group specific<br />
antigen-polyprotein genes <strong>of</strong> HIV play an<br />
important role in the virus replication cycle.<br />
Among them, viral protease catalyzes the<br />
formation <strong>of</strong> viral functional enzymes <strong>and</strong> proteins<br />
necessary for its survival. The viral particles at<br />
this stage are called virions. The virus particles<br />
after the protease action have all the necessary<br />
constituents <strong>of</strong> mature virus <strong>and</strong> are capable <strong>of</strong><br />
invading other T4 cells <strong>and</strong> repeating the life cycle<br />
<strong>of</strong> proviral DNA from viral RNA, the key stage<br />
in viral replication. Its central role in virus<br />
maturation makes protease is a prime target for<br />
anti-HIV-therapy.<br />
Computational chemistry has developed<br />
into an important contributor to rational drug<br />
design. Quantitative structure activity relationship<br />
(QSAR) modeling results in a quantitative<br />
correlation between chemical structure <strong>and</strong><br />
biological activity. QSAR analyses <strong>of</strong> HIV-1<br />
reverse transcriptase inhibitors (3), HIV-1<br />
Prediction <strong>of</strong> HIV-1 Protease Inhibitory Activity