Document Detail


Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.
MedLine Citation:
PMID:  16942019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Donglei Yu; Yojiro Sakurai; Chin-Ho Chen; Fang-Rong Chang; Li Huang; Yoshiki Kashiwada; Kuo-Hsiung Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  49     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-31     Completed Date:  2006-10-16     Revised Date:  2011-04-22    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5462-9     Citation Subset:  IM    
Affiliation:
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / chemical synthesis*,  chemistry,  pharmacology
Cell Line
Drug Resistance, Viral
HIV Protease Inhibitors / pharmacology
HIV-1 / drug effects
Humans
Lymphocytes / drug effects,  virology
Oleanolic Acid / analogs & derivatives*,  chemical synthesis,  chemistry,  pharmacology
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
AI-33066/AI/NIAID NIH HHS; R01 AI033066-17/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/HIV Protease Inhibitors; 508-02-1/Oleanolic Acid; 6713-27-5/moronic acid
Comments/Corrections

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