Principal factors affecting anti-integrase strand transfer activities of 1-hydroxy-2-oxo-1 and 8-naphthyridine-3-carboxamides HIV integrase strand transfer inhibitors (INSTIs)
KANG Jiaxiong1,2, LI Aixiu2,3, JIN Yurui2
1. Pharmacy Department of Sichuan Provincial Corps Hospital, Leshan 614000, China; 2. Drug Design Laboratory of Basic Courses Department of Logistics University of Chinese People's Armed Police Force, Tianjin 300309, China; 3. Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin 300309, China
Abstract：Objective To explore the principal microstructural factors affecting the anti-integrase strand transfer (INST) activities of 1-hydroxy-2-oxo-1 and 8-naphthyridine-3-carboxamides HIV integrase strand transfer inhibitors (INSTIs). Methods Using genetic function approximation method, ten 2d-quantitative structure-activity relationship (2D-QSAR) models of 1-hydroxy-2-oxo-1 and 8-naphthyridine-3-carboxamides INSTIs were constructed, from which the optimal one was chosen and the primary microstructural factors affecting the anti-INST activities of the inhibitors were analyzed. Results The no-cross-validated value (R2) of the optimal 2D-QSAR model was 0.8555, the leave one out cross-validated value (Q2loo) was 0.7761, and the external cross-validated value (R2ext) was 0.94. These parameters indicated that the model constructed possessed fairly statistical significance and stability. Conclusions The anti-INST activities of the 1-hydroxy-2-oxo-1 and 8-naphthyridine-3-carboxamides INSTIs are mainly correlated with the descriptors of JX, Dipole_mag, Jurs_PNSA_1 and Strain_Energy, which provides theoretical basis for the further rational design of the inhibitors.
康家雄, 李爱秀, 靳玉瑞. 影响1-羟基-2-氧-1,8-萘啶-3-甲酰胺类HIV整合酶链转移抑制剂抗整合酶链转移活性的主要因素[J]. 武警医学, 2022, 33(5): 390-394.
KANG Jiaxiong, LI Aixiu, JIN Yurui. Principal factors affecting anti-integrase strand transfer activities of 1-hydroxy-2-oxo-1 and 8-naphthyridine-3-carboxamides HIV integrase strand transfer inhibitors (INSTIs). Med. J. Chin. Peop. Armed Poli. Forc., 2022, 33(5): 390-394.
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