A novel series of ten substituted 4H-pyrimido [2,1-b] [1,3] benzothiazole curcumin derivatives have been synthesized and evaluated for their antimicrobial activity against Gram positive and Gram negative bacteria viz. Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus and against fungi viz. Alternaria solani, Aspergillus niger, Fusarium culmorum and Rhizopus stolonifer. The mechanism involves condensation of substituted benzaldehyde and curcumin via Knovenegal reaction which further reacts with substituted benzothiazole through Michael addition in the presence of pyridine catalyst using methanol as a solvent. The synthesized compounds were analyzed by elemental and spectral analysis.