Structure-Activity Relationships of Wollamide Cyclic Hexapeptides with Activity against Drug-Resistant and Intracellular Mycobacterium tuberculosis

Abstract

<jats:p> Wollamides are cyclic hexapeptides, recently isolated from an Australian soil <jats:italic>Streptomyces</jats:italic> isolate, that exhibit promising <jats:italic>in vitro</jats:italic> antimycobacterial activity against <jats:named-content content-type="genus-species">Mycobacterium bovis</jats:named-content> Bacille Calmette Guérin without displaying cytotoxicity against a panel of mammalian cells. Here, we report the synthesis and antimycobacterial activity of 36 new synthetic wollamides, collated with all known synthetic and natural wollamides, to reveal structure characteristics responsible for <jats:italic>in vitro</jats:italic> growth-inhibitory activity against <jats:named-content content-type="genus-species">Mycobacterium tuberculosis</jats:named-content> (H37Rv, H37Ra, CDC1551, HN878, and HN353).