Three known sesquiterpene lactones were isolated from Centratherum punctatum leaf extract. Their antibacterial properties and synergistic effects with ampicillin against drug-resistant Gram-negative bacteria were studied. Individually, they exerted little or no antibacterial activity against the bacterial strains. However, when combined with ampicillin, centratherin showed synergistic interaction against both bacterial strains. Centratherin reduced the MIC of ampicillin sixteen-fold. It portrayed potentiating effects when combined with the antibiotics.