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Abstract
As a continuation of our project aimed at a search for new antimycobacterial agents, several naturally occurring and synthetic compounds have been evaluated against Mycobacterium tuberculosis H37Rv and M. avium. Emphasis was placed on steroids and a series of isoprene long-chain alcohols to gain new insight into their structural activities. Maximum activity of isoprenoid derivatives seemed to depend on the hydrophobic chain length from the hydrophilic hydroxyl moiety. In contrast, ergosterol peroxide produced significantly greater inhibition than the corresponding steroids. Bile acids, amino acid-based surfactants and cholesteryl esters possessing different alkyl side chains were surprisingly the least effective. Encapsulation of compounds in cyclodextrins did not lead to significant loss in activity. Considering the inhibitory activity observed for the active steroids and isoprene long-chain alcohols, the phytyl moiety appeared to be critical for maximum activity. The implications of these findings for the rational design of new antituberculosis agents are briefly discussed.
Acknowledgement
This study was supported by a National Science Foundation CCLI grant (Award # 0837133) to the author (J.K.R.), and this support is gratefully acknowledged.