CHIANG MAI UNIVERSITY JOURNAL OF NATURAL SCIENCES

Volume 20, No. 01, Month JANUARY, Year 2021, Pages 1 - 12

Qsar-based design of the more potent betulinic acid derivatives as hiv maturation inhibitor

Ihsanul Arief, Harno Dwi Pranowo, Mudasir Mudasir, Karna Wijaya

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The maturation process on HIV life-cycles has become one of the targeted steps to inhibit these viruses. This process involves two kinds of proteins, namely HIV-protease and SP1-Gag. Betulinic acid (BA) and its derivatives had been known as potential inhibitors of HIV maturation. As their capability to modeling and also predict the activity of some analog compounds by using the descriptors, quantitative structure-activity relationship (QSAR) has been used to design more potent "new drugs" in recent years. Three-dimensional (3D) descriptors explained the topology of a compound and had proven to have relations to the compound"es biological activity. In this study, QSAR models were designed from 29 BA derivatives with HIV maturation inhibition activities. The best model involves 5 descriptors as follows: 1/logEC50 = -473.8 + (71.03 × TDB6u) + (764.7 × FPSA-3) + (-0.604 × RDF140u) + (0.882 × RDF80e) + (0.262 × PPSA-3) r2 = 0.792 SEE = 2.0305 Fcal/Ftab = 7.5621 r2test = 0.9798 Q2 = 0.9644 r2m = 0.9445 The QSAR model was then used to design and predict some of the new BA derivatives’ HIV maturation activities. The best predicted compound had 1/logEC50 value of -0.838 and EC50 value of 0.064 nM with the chemical name of 4‐[(1R,3aR,5aR,5bR,7aS,11aR,11bS,13aS,13bS)‐5a,5b,8,8,11b‐penta methyl‐1‐(prop‐1‐en‐2‐yl)‐3a[({2‐[4‐(pyrimidin‐2‐yl)piperazin‐1‐yl]ethyl} amino)methyl]‐icosahydro‐1H-cyclo penta[a]chrysen‐9‐yl]benzoic acid. The synthetic route to the proposed compound also suggested in this report.

Keywords

Betulinic acid, Drug design, HIV maturation inhibitor, QSAR

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