Certain 1-ethyl- and 1-aryl-6-fluoro-1,4-dihydroquinol-4-one derivatives were synthesized and evaluated for antimycobacterial and cytotoxic activities. Preliminary results indicated that, for 1-aryl-6-fluoroquinolones, both 7-(piperazin-1-yl)- and 7-(4-methylpiperazin-1-yl) derivatives, 9b and 11a, are able to completely inhibit the growth of M. tuberculosis at a concentration of 6.25 μg/ml, while the 7-[4-(2-oxo-2-phenylethyl)piperazin-1-yl] derivative 13 exhibits only 31% growth inhibition at the same concentration. For 1-ethyl-6-fluoroquinolones, both 7-[4-(2-oxopropyl)piperazin-1-yl]- and 7-[4-(2-oxo-2-phenylethyl)piperazin-1-yl]-derivatives, 2a and 2b, respectively, show complete inhibition, while their 2-iminoethyl and substituted phenyl counterparts 3a and 2c are less active. In addition, the 6,8-difluoro derivative was a more-favorable inhibitor than its 6-fluoro counterpart (2bvs.2d). These results deserve full attention especially because 2a, 2b, 9b, and 11a are non-cytotoxic at a concentration of 100 μM. Furthermore, compound 9b proved to be a potent anti-TB agent with selective index (SI)>40 and an EC90 value of 5.75 μg/ml.