Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.
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.
Yu
Donglei
D
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Sakurai
Yojiro
Y
Chen
Chin-Ho
CH
Chang
Fang-Rong
FR
Huang
Li
L
Kashiwada
Yoshiki
Y
Lee
Kuo-Hsiung
KH
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; C023607:moronic acid; D009828:Oleanolic Acid