Highly active antimycobacterial derivatives of benzoxazine

New 3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The antimycobacterial activity increased with the replacement of the carbonyl group by the thiocarbonyl group in the starting 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-diones. The most active derivatives were more active than isonicotinhydrazide (INH). Free-Wilson analysis was also carried out and the activity contribution was examined.