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J Med Chem. 2006 Sep 7;49(18):5462-9.

Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.

Author information

1
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Abstract

In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 microM against NL4-3, 0.021 microM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 microM against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

PMID:
16942019
PMCID:
PMC2512972
DOI:
10.1021/jm0601912
[Indexed for MEDLINE]
Free PMC Article

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