MRSA pyruvate kinase inhibitory activity of synthetically derived thiazole containing deoxytopsentin analogues

The health care crisis caused by methicillin resistant Staphylococcus aureus (MRSA) is due in part to a lack of fundamental drug discovery research into new antibiotics with novel modes of action. Marine bis-indole alkaloids have proved to be effective in vitro antibacterials. We present the synthesis of thiazole containing analogues of the marine natural product MRSA pyruvate kinase (PK) inhibitor, 6-bromodeoxytopsenin. The synthetic analogues showed moderate activity compared to the marine natural product against MRSA PK, an evolutionary conserved hub protein critical for bacterial survival. Our synthesis, via a Hantzsch thiazole condensation of α-oxo-1H-indole-3-thioacetamides with 2-bromo-1-(1H-indol-3-yl)-ethanones provided several challenges.