| Summary: | We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4<i>H</i>-chromen-4-one (<b>1</b>) and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine (<b>2</b>) and 2-chloro-5-<i>n</i>-nonylpyrimidine (<b>3</b>) in vitro against <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>, H37Ra) and <i>Mycobacterium avium (M. avium)</i>, using a Microplate Alamar Blue Assay (MABA). The effects of the compounds <b>1</b>–<b>3</b> in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of <i>M. tuberculosis</i> and <i>M. avium</i> were also evaluated in in vitro assays. As a single agent, compounds <b>1</b> and <b>2</b> exhibited modest activity while compound <b>3</b> was the most effective against <i>M. tuberculosis</i> and <i>M. avium</i>. When compounds <b>1</b>–<b>3</b> were evaluated at lower than 50% of their inhibitory concentrations in a two-drug combination with isoniazid or rifampicin, they showed additive to synergistic interactions. This inhibitory effect was improved when each of the three compounds was tested together in a three-drug combination with two of the first-line anti-TB drugs. Compounds <b>1</b>–<b>3</b> also demonstrated strong synergistic interaction in combination with cycloserine and clarithromycin in inhibiting the growth of <i>M. tuberculosis</i> and <i>M. avium</i>, respectively. This study demonstrated that compounds <b>1</b>–<b>3</b> have potential to be developed as effective anti-TB agents with combined use.
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