New series of thiazolyl hydrazones were designed and synthesized via the reaction of benzophenone thiosemicarbazone 2 with chloroacetic acid, (un)substituted phenacylbromide and ethyl-2-chloroacetoacetate to yield compounds 3, 5a-d & 6 respectively. Furthermore, reaction of the thiazolidin-4-one 3 with aromatic aldehydes afforded compounds 4a-g. Characterization data, along with in vitro antimicrobial activity for all compounds are herein reported. All the synthesized compounds were screened against Methicillin- Resistant Staphylococcus aureus (MRSA), E. coli, K. pneumonia, P. aeruginosa, A baumannii, C. albicans and C. neoformans var.grubii. Compounds 2 and 4e showed the highest bacterial growth inhibition with 28.6% and 28.7% against MRSA, respectively. Moreover, the trisubstituted thiazole derivative 6 was the most active compound against Gram-negative bacteria A. baumannii with 59% growth inhibition. Furthermore, compounds 4e & 6 showed 22.5% and 17.3% decrease in peptidoglycan density, respectively. Molecular docking into bacterial MurB enzyme active site was used to determine their binding modein which they showed good interactions with Gln229, Arg225 and Ser82 amino acid residues.