Somsak Ruchirawat

Beta-(1-adamantylthio)pyridine analogs as antimicrobials and antimalarials

An array of interesting activities for bioactive 3-substituted thiopyridines have previously been reported. Herein, a series of αand β-(1-adamantylthio) analogs of 3-picoline and phenylpyridines were prepared and investigated for antimicrobial (agar dilution method against 21 strains of microorganisms) and antimalarial (against P. falciparum) activities. It was found that β-thiopyridines, 5-(1-adamantylthio)-3-picoline (7) and 3-(1-adamantylthio)-4phenylpyridine (8) are novel antimicrobials and antimalarials. Significantly, analogs 7 and 8 are very potent antimicrobials with MIC range of 2-32 μg/mL where 8 being the most potent. The β-sulfides 7 and 8 selectively inhibited the growth of tested gram-positive bacteria, but inactive against gram-negative bacilli including the members of Enterobacteriaceae. This study identified new antimicrobials that represent promising lead compounds suitable for further preclinical and clinical development.