Anti-Mycobacterial Activity of Flavonoid and Pyrimidine Compounds.

We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4 H -chromen-4-one ( 1 ) and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine ( 2 ) and 2-chloro-5- n -nonylpyrimidine ( 3 ) in vitro against Mycobacterium tuberculosis ( M. tuberculosis , H37Ra) and Mycobacterium avium (M. avium) , using a Microplate Alamar Blue Assay (MABA). The effects of the compounds 1 - 3 in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of M. tuberculosis and M. avium were also evaluated in in vitro assays. As a single agent, compounds 1 and 2 exhibited modest activity while compound 3 was the most effective against M. tuberculosis and M. avium . When compounds 1 - 3 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 1 - 3 also demonstrated strong synergistic interaction in combination with cycloserine and clarithromycin in inhibiting the growth of M. tuberculosis and M. avium , respectively. This study demonstrated that compounds 1 - 3 have potential to be developed as effective anti-TB agents with combined use.