Anti-AIDS agents 66: syntheses and anti-HIV activity of phenolic and aza 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) derivatives.
New phenolic and aza 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogs were synthesized and assayed for inhibition of HIV-1 IIIB replication in H9 lymphocytes. Compound 16, 4-methyl-1'-aza-DCK (4-methyl-aza-DCK), was less lipophilic than 4-methyl-DCK, and retained sub-micromolar anti-HIV activity with EC(50) and TI values of 0.77 microM and >42, respectively. Moreover, it showed moderately improved metabolic stability. Introduction of phenolic hydroxyl groups to 4-methyl-DCK decreased lipophilicity significantly, but did not improve metabolic stability and also decreased activity.
Suzuki
Madoka
M
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Yu
Donglei
D
Morris-Natschke
Susan L
SL
Smith
Philip C
PC
Lee
Kuo-Hsiung
KH
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002164:Camphor / Q000031:analogs & derivatives* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects*
C479985:3'R,4'R-di-O-(-)-camphanoyl-(+)-cis-khellactone; D019380:Anti-HIV Agents; D007783:Lactones; D010636:Phenols; D002164:Camphor