Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid.
Four new tetragalloylquinic acids, 3,5-di-O-galloyl-4-O-digalloylquinic acid, 3,4-di-O-galloyl-5-O-digalloylquinic acid, 3-O-digalloyl-4,5-di-O-galloylquinic acid, and 1,3,4,5-tetra-O-galloylquinic acid, were isolated and characterized from a commercial tannic acid as a new class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitor. Compounds 2, 3, and 4 inhibit HIV RT activity 90, 89, and 84% at 100 microM and 73, 70, and 63% at 30 microM, respectively. Compounds 2-5 also inhibit the HIV growth in cells in the range of 61-70% with low cytotoxicity at 25 microM. The HIV cell growth inhibitory effects of these compounds at 25 microM and 6.25 microM (44-57%) are comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively. The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT.
Nishizawa
M
M
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Yamagishi
T
T
Dutschman
G E
GE
Parker
W B
WB
Bodner
A J
AJ
Kilkuskie
R E
RE
Cheng
Y C
YC
Lee
K H
KH
D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology; D002478:Cells, Cultured; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D006801:Humans; D047348:Hydrolyzable Tannins / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D019384:Nucleic Acid Synthesis Inhibitors; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013634:Tannins
D000998:Antiviral Agents; D047348:Hydrolyzable Tannins; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013634:Tannins; D011801:Quinic Acid; C061728:1,3,4,5-tetra-O-galloylquinic acid; C061725:3,5-di-O-galloyl-4-O-digalloylquinic acid; C061726:3,4-di-O-galloyl-5-O-digalloylquinic acid; C061727:3-O-digalloyl-4,5-di-O-galloylquinic acid; D005707:Gallic Acid