Discovery of a semi-synthesized cyclolignan as a potent HIV-1 non-nucleoside reverse transcriptase inhibitor

• Published in: Journal of asian natural products research Vol. 21; no. 1; pp. 76 - 85
• Main Authors: Guo, Jia-Mei, Ba, Ming-Yu, Yang, Ying, Yao, Chun-Suo, Yu, Miao, Shi, Jian-Gong, Guo, Ying
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-01-2019; Taylor & Francis Ltd
• Subjects: Antiretroviral agents; Antiretroviral drugs; Antiviral activity; Cyclolignan; Deoxyribonucleic acid; DNA; DNA polymerase; DNA-directed DNA polymerase; DNA-directed RNA polymerase; drug combinations; drug resistance; Highly active antiretroviral therapy; HIV; HIV-1; Human immunodeficiency virus; Lamivudine; non-nucleoside reverse transcriptase inhibitor; Non-nucleoside reverse transcriptase inhibitors; Nucleosides; Pharmacodynamics; Pharmacology; Ribonucleic acid; RNA; RNA-directed DNA polymerase; Synergistic effect; Synthesis; Tenofovir; Viruses; Zidovudine; HIV-1; drug resistance; Cyclolignan; drug combinations; non-nucleoside reverse transcriptase inhibitor
• ISSN: 1028-6020; 1477-2213
• DOI: 10.1080/10286020.2017.1417266

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 (HIV-1) infection. In this study, we identified (+)-(7′S,8S,8'S)-3′,4,4′,5,5′-pentamethoxy-2,7′-cyclolignan (SG-1), a cyclolignan semi-synthesized from Machilus robusta and M. wangchiana extracts, as a potent NNRTI. SG-1 displayed anti-HIV-1 activity with an IC
50
of 0.77 μmol/L by inhibiting reverse transcriptase (RT) RNA-dependent DNA polymerase activity through a direct binding. It had synergistic effects when combined with tenofovir/lamivudine or zidovudine/lamivudine. The pharmacodynamics properties of SG-1 render it a valuable lead for the development of novel NNRTIs.