Due to chalcone compounds' diverse and intriguing bioactive characteristics, the present work recommends the production of several new chalcone derivatives, followed by spectral characterization utilizing various spectral techniques such as IR, NMR, and elemental analyses. In addition to, assessment the antimicrobial activity of imidazo[1,2-c] pyrimidine derivatives. All tested new chalcone compounds showed antibacterial activity against P. aeruginosa and B. subtilis, while only compounds (5a-d and 5f) displayed activity against E. coli. Furthermore, only compounds (5a-c, 5e and 5f) reduced the development of S. aureus. The compound 5f revealed significant antibacterial activity against S. aureus (87.5%), B. subtilis (82.61 %), P. aeruginosa (78.26%) and E. coli (64%), when compared to Ampicillin. On the other hand, the compounds (5a-d, 5e and 5f) showed antifungal activity against C. Albicans. Also, compounds (5a, 5b, 5c, 5d and 5f) displayed activity against A. flavus. A significant antifungal activity for compound 5b has been observed against C. Albicans (70.37%) and A. flavus (52%), when compared to Colitrima-zole.