Synthesis of a recently discovered S-methylated quinolone natural product (1) was carried out, in addition to the production of a range of 2-substituted 4-quinolone derivatives (2-11). Two approaches were used: (i) the base-catalyzed cyclization of N-(ketoaryl)amides; (ii) attachment of the substituent to the quinolone core via a Suzuki-Miyaura cross-coupling. Also produced were a small suite of related 2(1H)-quinolones (12-19). The synthesized compounds were assessed for their antimicrobial properties. The alkene-substituted 4-quinolone 8 significantly inhibited the growth of a Pseudomonas aeruginosa strain, and both 4-quinolones and 2(1H)-quinolones were capable of inhibiting the swarming behavior of Bacillus subtilis.