Medina-Franco José Luis, Rodríguez-Morales Sergio, Juárez-Gordiano Cecilia, Hernández-Campos Alicia, Jiménez-Barbero Jesús, Castillo Rafael
Departamento de Farmacia, Facultad de Química, UNAM, CU, DF 04510, Mexico.
Bioorg Med Chem. 2004 Dec 1;12(23):6085-95. doi: 10.1016/j.bmc.2004.09.008.
Potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of the pyridinone derivative type were docked into nine NNRTIs binding pockets of HIV-1 reverse transcriptase (RT) structures. The docking results indicate that pyridinone analogues adopt a butterfly conformation and share the same binding mode as the crystal inhibitors in the pocket geometries of nevirapine, 1051U91, 9-Cl-TIBO, Cl-alpha-APA, efavirenz, UC-781, and S-1153. The results are in agreement with the data concerning mutational and structure-activity relationships available for pyridinone analogues and aid in the understanding, at the molecular level, of the biological response of published hybrid pyridinone molecules. Strategies to design further pyridinone derivatives active against RT containing mutations are discussed.
将吡啶酮衍生物类型的强效非核苷逆转录酶抑制剂（NNRTIs）对接至HIV-1逆转录酶（RT）结构的九个NNRTIs结合口袋中。对接结果表明，吡啶酮类似物呈蝴蝶构象，并且在奈韦拉平、1051U91、9-氯-TIBO、氯-α-APA、依非韦伦、UC-781和S-1153的口袋几何结构中，与晶体抑制剂具有相同的结合模式。这些结果与有关吡啶酮类似物的突变和构效关系的数据一致，并有助于在分子水平上理解已发表的杂合吡啶酮分子的生物学反应。讨论了设计对含有突变的RT具有活性的进一步吡啶酮衍生物的策略。
