A series of sulfur attached quinolines and quinoline–coumarin bisheterocycles have been synthesized by the Friedlander reaction of methyl 2-[(2,4-diaryl-3 quinolyl)sulfanyl]acetate and subsequent reaction with salicylaldehyde. These compounds were screened for their in vitro antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungal pathogen. Among the 19 compounds screened, preliminary results indicated that many of the compounds demonstrated moderate to good antimicrobial activities. The cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro were evaluated for the most active compound, which displayed no toxic effects.