School of Chinese Medicine
Justicia gendarussa, a medicinal plant collected in Vietnam, was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant extracts. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A (1). Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drug AZT. Patentiflorin A and two congeners were synthesized, de novo, as an efficient strategy for resupply as well as for further structural modification of the anti-HIV ANL glycosides in the search for drug leads. Subsequently, it was determined that the presence of a quinovopyranosyloxy group in the structure is likely essential to retain the high degree of anti-HIV activity of this type of compounds. Patentiflorin A was further investigated against the HIV-1 gene expression of the R/U5 and U5/gag transcripts, and the data showed that the compound acts as a potential inhibitor of HIV-1 reverse transcription. Importantly, the compound displayed potent inhibitory activity against drug-resistant HIV-1 isolates of both the nucleotide analogue (AZT) and non-nucleotide analogue (nevaripine). Thus, the ANL glycosides have the potential to be developed as novel anti-HIV drugs.
Source Publication Title
Journal of Natural Products
American Chemical Society
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Natural Products, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.jnatprod.7b00004.
This project was supported by the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKBU 262912), the Health and Medical Research Fund (12132161) of the Food and Health Bureau, Hong Kong SAR, the Hong Kong Baptist University (HKBU) Interdisciplinary Research Matching Scheme (RC-IRMS/15-16/02), Faculty Research Grants, Hong Kong Baptist University (FRG2/11- 12/134 and FRG2/14-15/047), NIH Grants 3U01TW001015- 10S1 and 2U01TW001015-11A1, administered by the Fogarty International Center as part of an International Cooperative Biodiversity Groups (ICBG) program, through funds from NIH, NSF, and Foreign Agricultural Service of the USDA, and Mr. Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund.
Link to Publisher's Edition
Zhang, H., Rumschlag-Booms, E., Guan, Y., Wang, D., Liu, K., Li, W., Nguyen, V., Cuong, N., Soejarto, D., Fong, H., & Rong, L. (2017). Potent inhibitor of drug-resistant HIV-1 strains identified from the medicinal plant Justicia gendarussa. Journal of Natural Products, 80 (6), 1798-1807. https://doi.org/10.1021/acs.jnatprod.7b00004