A series of six novel Imidazole derivatives, with natural nucleobases by mono, di and tri substitution in 2, 4, 5- Tribromo Imidazole at the 2, 4 – and 5 – position was synthesized. Target molecules were synthesized by stoichiometric addition of various nucleophiles to 2,4,5 – Tribromo Imidazole in the presence of suitable base. The newly synthesized Imidazole derivatives have been characterized by IR, 1H NMR, 13C NMR (1D, 2DNMR), mass spectral and elemental analysis. All the synthesized compounds were screened for in vitro and microbial activity against a panel of selected bacterial and fungal strains using streptomycin and Amphotericin B as standards.