Structure, stereochemistry, and biological activity of integramycin, a novel hexacyclic natural product produced by Actinoplanes sp. that inhibits HIV-1 integrase.
[structure: see text] HIV-1 integrase is a critical enzyme for viral replication, and its inhibition is an emerging target for potential antiviral chemotherapy. We have discovered a novel inhibitor, integramycin, from screening of fermentation extracts using an in vitro assay. Integramycin possesses a hexacyclic ring system and exhibited an IC50 value of 4 microM against HIV-1 integrase (strand transfer). The isolation, structure elucidation, stereochemistry, conformation, and biological activity has been described.
Singh
Sheo B
SB
Merck Research Laboratories, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
Zink
Deborah L
DL
Heimbach
Brian
B
Genilloud
Olga
O
Teran
Ana
A
Silverman
Keith C
KC
Lingham
Russell B
RB
Felock
Peter
P
Hazuda
Daria J
DJ
D005285:Fermentation; D019428:HIV Integrase Inhibitors / Q000737:chemistry*; D015497:HIV-1; D009682:Magnetic Resonance Spectroscopy; D008848:Micromonosporaceae / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology
D019428:HIV Integrase Inhibitors; D009281:Naphthalenes; D013141:Spiro Compounds; C489772:integramycin