TY - JOUR JF - mazums-pbr JO - Pharm Biomed Res VL - 5 IS - 2 PY - 2019 Y1 - 2019/4/01 TI - Computer-aided rational design of acyclovir analogs to inhibit purine nucleoside phosphorylase TT - N2 - 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. SP - 38 EP - 48 AU - Selsi, Nusrat Jahan AU - Barua, Lira AU - Bhattacharjee, Debpriya AU - Rahman, Gulamur AU - Zannat, Syeda Sakiatuz AU - Munia, Najia Absar AU - Fahad, Rubaiyat AU - Bipasha, Tanjiba Harun AU - Rahman, Azizur AU - Dash, Raju AD - Department of Anatomy, Dongguk University Graduate School of Medicine, Gyeongju, Korea KW - Purine nucleoside phosphorylase KW - halogen KW - acyclovir KW - analogs KW - T-cell lymphoma KW - molecular docking simulation UR - http://pbr.mazums.ac.ir/article-1-252-en.html DO - 10.18502/pbr.v5i2.1584 ER -