A series of curcumin derivatives containing heterocyclic moiety have been synthesized and evaluated for their antibacterial activities. The chemical structures of the synthesized compounds were verified on the basis of spectral data and elemental analyses. Investigation of antimicrobial activity of the derivatives demonstrated the ability to inhibit Gram-positive microorganisms with zone of inhibition ranging from 14-18 mm, MIC ranging between 0.0625 and 0.25 mg/mL. Among all tested derivatives, diazepine 4 exhibited remarkable potency against Gram-positive bacteria S. aureus. An extensive study is underway to optimize the effectiveness of diazepine type of compounds and to determine their mode of action.