PMID- 1379639
OWN - NLM
STAT- MEDLINE
DCOM- 19920904
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 35
IP  - 15
DP  - 1992 Jul 24
TI  - The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the 
      tropical rainforest tree, Calophyllum lanigerum.
PG  - 2735-43
AB  - Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided 
      fractionation of an extract of Calophyllum lanigerum. The structures of 
      calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), 
      calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related 
      derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly 
      HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of 
      calanolide A (1) and calanolide B (4) was established by a modified Mosher's 
      method. Calanolides A (1) and B (4) were completely protective against HIV-1 
      replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, 
      respectively), but were inactive against HIV-2. Some of the related compounds 
      also showed evidence of anti-HIV-1 activity. Studies with purified bacterial 
      recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 
      specific RT inhibitors. Moreover, calanolide A was active not only against the 
      AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant 
      A17 strain. This was of particular interest since the A17 virus is highly 
      resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., 
      TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently 
      common pharmacologic class. The calanolides represent a substantial departure 
      from the known class and therefore provide a novel new anti-HIV chemotype for 
      drug development.
FAU - Kashman, Y
AU  - Kashman Y
AD  - Laboratory of Drug Discovery Research and Development, Frederick Cancer Research 
      and Development Center (NCI-FCRDC), Maryland 21702-1201.
FAU - Gustafson, K R
AU  - Gustafson KR
FAU - Fuller, R W
AU  - Fuller RW
FAU - Cardellina, J H 2nd
AU  - Cardellina JH 2nd
FAU - McMahon, J B
AU  - McMahon JB
FAU - Currens, M J
AU  - Currens MJ
FAU - Buckheit, R W Jr
AU  - Buckheit RW Jr
FAU - Hughes, S H
AU  - Hughes SH
FAU - Cragg, G M
AU  - Cragg GM
FAU - Boyd, M R
AU  - Boyd MR
LA  - eng
GR  - N01-CO-74101/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Antiviral Agents)
RN  - 0 (Coumarins)
RN  - 0 (Pyranocoumarins)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 142632-33-5 (calanolide B)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - S5A9TQN46W (calanolide A)
SB  - IM
EIN - J Med Chem 1993 Apr 16;36(8):1110
MH  - Antiviral Agents/chemistry/isolation & purification/*pharmacology
MH  - Chromatography, Liquid
MH  - Coumarins/chemistry/isolation & purification/*pharmacology
MH  - Cytopathogenic Effect, Viral/drug effects
MH  - Drug Resistance, Microbial
MH  - HIV Reverse Transcriptase
MH  - HIV-1/*drug effects/enzymology/physiology
MH  - HIV-2/drug effects/physiology
MH  - Humans
MH  - Hydrolysis
MH  - Magnetic Resonance Spectroscopy
MH  - Pyranocoumarins
MH  - Reverse Transcriptase Inhibitors
MH  - Structure-Activity Relationship
MH  - Trees/*chemistry
MH  - Tumor Cells, Cultured
MH  - Virus Replication/drug effects
EDAT- 1992/08/03 19:15
MHDA- 2001/03/28 10:01
CRDT- 1992/08/03 19:15
PHST- 1992/08/03 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1992/08/03 19:15 [entrez]
AID - 10.1021/jm00093a004 [doi]
PST - ppublish
SO  - J Med Chem. 1992 Jul 24;35(15):2735-43. doi: 10.1021/jm00093a004.