Ahmpatinin iBu, a new HIV-1 protease inhibitor, from Streptomyces sp. CPCC 202950.

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. This journal is © The Royal Society of Chemistry.

Citation

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. Ahmpatinin iBu, a new HIV-1 protease inhibitor, from Streptomyces sp. CPCC 202950. RSC advances. 2018 Jan 29;8(10):5138-5144

PMID: 35542440

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