Integrasone Derivatives Isolated from Lepteutypa sp. KT4162 and Their Anti-HIV-1 Integrase Activity

  • J Nat Prod. 2023 Apr 28;86(4):1019-1024. doi: 10.1021/acs.jnatprod.3c00065.
Satomi Miura  1 ,  Kotaro Ishida  2 ,  Kazuaki Tanaka  1 ,  Eiji Morita  1 ,  Masaru Hashimoto  1
Affiliations
  • 1. Faculty of Agriculture and Life Science, Hirosaki University, 3-Bunkyo-cho, Hirosaki 036-8561, Japan.
  • 2. The United Graduate School of Agricultural Sciences, Iwate University, Morioka 020-8550, Japan.
PMID: 36898139 DOI: 10.1021/acs.jnatprod.3c00065
Abstract

Five integrasone derivatives, integrasone C (1), isointegrasone C (2), integrasone D1 (3), integrasone D2 (4), and integrasone E (5), were isolated from the culture broth of Lepteutypa sp. KT4162. Neither conventional NMR analyses nor DFT (density functional theory)-based computationally assisted chemical shift discussions were sufficient to elucidate the relative configuration of the 1,4-epoxydiol moiety. A combined analysis using the calculated nJCH values and HMBC spectra was helpful to establish the relative configuration. The absolute configurations of 1-5 were determined using DFT-based ECD (electronic circular dichroism) spectral analysis. Biological assays of these compounds revealed that 2 potently inhibits HIV-1 integrase without cytotoxicity.