ABSTRACT
Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.
Subject(s)
HIV Integrase Inhibitors/chemistry , HIV Integrase Inhibitors/pharmacology , HIV-1/drug effects , Quinic Acid/analogs & derivatives , Quinic Acid/pharmacology , Cell Line , HIV Integrase Inhibitors/chemical synthesis , HIV-1/enzymology , Humans , Models, Molecular , Quinic Acid/chemistry , Structure-Activity RelationshipABSTRACT
Trypanocidal activity of a number of lipophilic diamines and amino alcohols was evaluated in vitro against Trypanosoma cruzi blood stream forms. Several of the studied compounds showed inhibition of T. cruzi growth. The most active ones were compounds 3, 4 and 5 with a IC50 of 31.2 µg/mL, activity similar to the reference drug crystal violet.
