Volume 5, Issue 2 (2019)
Pharm Biomed Res 2019, 5(2): 38-48 |
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Selsi N J, Barua L, Bhattacharjee D, Rahman G, Zannat S S, Munia N A, et al . Computer-aided rational design of acyclovir analogs to inhibit purine nucleoside phosphorylase. Pharm Biomed Res 2019; 5 (2) :38-48
URL: http://pbr.mazums.ac.ir/article-1-252-en.html
URL: http://pbr.mazums.ac.ir/article-1-252-en.html
Nusrat Jahan Selsi1 
, Lira Barua2 , Debpriya Bhattacharjee1 , Gulamur Rahman1 , Syeda Sakiatuz Zannat3 , Najia Absar Munia4 , Rubaiyat Fahad1 , Tanjiba Harun Bipasha1 , Azizur Rahman5 , Raju Dash * 6
, Lira Barua2 , Debpriya Bhattacharjee1 , Gulamur Rahman1 , Syeda Sakiatuz Zannat3 , Najia Absar Munia4 , Rubaiyat Fahad1 , Tanjiba Harun Bipasha1 , Azizur Rahman5 , Raju Dash * 6
1- Department of Pharmacy, University of Science and Technology Chittagong, Bangladesh
2- Department of Chemistry, University of Chittagong, Chittagong, Bangladesh
3- Department of Physics, Astronomy and Mathematics, Faculty of Science and Technology University of Central Lancashire, Lancashire, United Kingdom
4- Department of Pharmacy, BGC Trust University Bangladesh, Chandanaish, Bangladesh
5- Department of Pharmacy, Southern University Bangladesh, Chittagong, Bangladesh
6- Department of Anatomy, Dongguk University Graduate School of Medicine, Gyeongju, Korea
2- Department of Chemistry, University of Chittagong, Chittagong, Bangladesh
3- Department of Physics, Astronomy and Mathematics, Faculty of Science and Technology University of Central Lancashire, Lancashire, United Kingdom
4- Department of Pharmacy, BGC Trust University Bangladesh, Chandanaish, Bangladesh
5- Department of Pharmacy, Southern University Bangladesh, Chittagong, Bangladesh
6- Department of Anatomy, Dongguk University Graduate School of Medicine, Gyeongju, Korea
Abstract: (2673 Views)
Purine nucleoside phosphorylase (PNP) is one of the major enzymes in the purine salvage pathway. It is responsible for the elevation of deoxyguanosine, and thus considered as the potent target in T-cell lymphoma. The present study examined acyclovir, reported as a low-affinity PNP inhibitor, for the rational design of new acyclovir derivatives by incorporating halogens, hydroxyl, and bulky amino groups. The molecular actions of designed derivatives were investigated by employing density functional theory, molecular docking, and binding energy calculations. The results revealed that the newly designed compounds were highly stable and showed more affinity to PNP than the parent compound, acyclovir. The quantum mechanics and molecular docking studies suggested that modification of side chains with bulky polar groups provided better binding affinities than substitutions with halogens. The resultant derivatives have strong polar interactions like His257 and Tyr88. Furthermore, the designed derivatives were within the ideal range of ADMET (absorption, distribution, metabolism, elimination, and toxicity) analysis. Considering that, these findings recommend further validation of designed acyclovir derivatives in wet lab confirmatory analysis with the emphasis on the further improvements in the treatment of T-cell-mediated diseases.
Keywords: Purine nucleoside phosphorylase, halogen, acyclovir, analogs, T-cell lymphoma, molecular docking simulation
Type of Study: Original Research |
Subject:
Mollecular Modeling
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