Synthetic piperine amide analogues with antimycobacterial activity

Abstract

Piperine amide analogues are synthesized by replacement of the piperidine moiety with different types of cyclic amines, including adamantyl and monoterpene derived fragments. The compounds are screened for activity against Mycobacterium tuberculosis H37Rv. The most potent compounds are the 1-adamantyl and the monoterpene derived hybrids, which combine nanomolar antimycobacterial activity with low cytotoxicity against human cells. The presence of quaternary carbon atom as main structural requirement for anti-TB activity is pointed out by a QSAR study. The most promising compound is the (+)-isopinocampheylamine derived amide which is characterized with selectivity index of 1387.8.

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A series of Piperine amide analogues are synthesized by replacing piperidine moiety with different types of cyclic amines, including cyclohexyl, bicyclo[2.2.1]heptyl, adamantyl and monoterpene derived fragments. The hybrid analogues with 1-adamantyl and the monoterpene fragments displayed nanomolar antimycobacterial activity with low cytotoxicity against human cells. A QSAR study pointed out the presence of quaternary carbon atom as main structural requirement for the activity. The most promising compound is the (+)-isopinocampheylamine derived amide, with selectivity index of 1387.8.

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