Title
Ahmpatinin iBu, a new HIV-1 protease inhibitor, fromStreptomyces sp. CPCC 202950
Author
Ming-Hua Chen, Shan-Shan Chang, Biao Dong, Li-Yan Yu, Ye-Xiang Wu, Ren-Zhong Wang, Wei Jiang, Zeng-Ping Gao, Shu-Yi Si
Year
2018
Journal
RSC Advances
Abstract
Ahmpatinin iBu (1) and statinin iBu (2), two new linear peptides, a novel pyrrolidine derivative, (−)-(S)-2-[3-(6-methylheptanamido)-2-oxopyrrolidin-1-yl] acetic acid (3), and three known pepstatin derivatives (4–6) along with their corresponding methanolysis artifacts (7–9) were isolated from Streptomyces sp. CPCC 202950. Their structures were elucidated on the basis of extensive spectroscopic data using Marfey's analysis, chiral-phase HPLC, and ECD and OR calculation to determine the absolute configurations. Compound 1 contains an unusual amino acid, 4-amino-3-hydroxy-5-(4-methoxyphenyl)pentanoic acid (Ahmppa), and 3 is the first natural product with a 2-(3-amino-2-oxopyrrolidin-1-yl)acetic acid system. Compounds 1, 2, and 4–9 are HIV-1 protease inhibitors. In particular, ahmpatinin iBu (1) exhibits significant inhibitory activity against HIV-1 protease with an IC50 value of 1.79 nM. A preliminary structure–activity relationship is discussed.
Instrument
J-815
Keywords
Circular dichroism, Absolute configuration, Natural products, Medicinal