Obesity has emerged as the root cause for various metabolic disorders worldwide and hence demands for urgent attention. In the same stride, a series of quinoline carboxylic acid-based styryl/alkyne hybrids were designed, synthesized, and evaluated for their anti-adipogenic activity. Based on the structure-activity relationship, functional groups and essential substituents to potentiate the anti-adipogenic activity were identified. The potent compound (E)-6-fluoro-2-(4-(4-methylstyryl)phenyl)quinoline-4-carboxylic acid (5m) suppresses the adipogenesis with IC