Design, synthesis and biological potentials of novel tetrahydroimidazo[1,2-a]pyrimidine derivatives

A novel series of 5-(substituted aldehyde)-7-methyl-3-oxo-N-phenyl-2-((3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-yl)methylene)-1,2,3,5-tetrahydroimidazo[1,2-a]pyrimidine-6-carboxamide analogues (1-24) was synthesized using the Biginelli condensation.

The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In the series, compound 15 exhibited significant antimicrobial activity against Candida albicans and Aspergillus niger with MIC value = 1.04 × 10^-2 µM/ml and compound 2 was found to be most active antioxidant agent with IC₅₀ value = 46.31 using DPPH assay. Anticancer activity results indicated that compound 23 displayed better anticancer activity against human breast cancer cell line (MCF-7) with GI₅₀ value = 34.78 using SRB assay.

All synthesized derivatives exhibited good antimicrobial, antioxidant and anticancer activity using specific method and compared with standard drugs, especially compounds 2, 15 and 23 displayed more activity than reference drugs. Structure activity relationship demonstrated that presence of electron releasing groups of the synthesized compounds enhanced the antibacterial activity against Escherichia coli as well as antioxidant activity and electron withdrawing groups improved the antimicrobial as well as anticancer activity against human breast (MCF-7) cancer cell line.