Objective: New compounds were designed and synthesized using sulfomethoxazole and amino acids with metabolically stable linkers, suspected to be act on fungal and bacterial carbonic anhydrase enzymes which are necessary for their metabolic activities. Methods: N-acylation of sulfomethxazole aromatic amine using chloroacetyl chloride with basic medium (10 %NaOH) solution, giving compound I (an alkyl halide). Then a coupling reaction between compound I and carboxylic acid of Boc- (valine, phenylalanine, histidine) giving compounds (IIa,IIIa,IVa) respectively via both amide and ester linkage. Then deprotection of amino acid amine occurred by acidolysis of tert-butoxy carbonyl group of the three compounds using trifluoracetic acid (TFA). This reaction gave us new compounds (Vb, VIb, VIIb) respectively. Agar Well Diffusion method evaluated the antimicrobial activity. Four types of bacteria (Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa and Klebseilla species) and one type of fungi (Candida albicans) were used in in-vitro study. All the titled compounds characterized and identified by elemental microanalysis and I.R spectra study. Results: All the synthesized compounds -comparing with sulfomethoxazole as a reference standard- have good antibacterial activity against Gram-negative bacteria (Pseudomonas aeruginosa), and against Candida albicans. compounds IIIa, Vb,VIb and VIIb also show a good inhibition to Gram-positive bacteria growth (Staphylococcus aureus and Streptococcus pneumonia). Conclusion: The results of this study indicate that the new designed compounds possess a higher antibacterial and anti-fungal activity in comparison to sulfomethoxazole, and their higher activity may be come from their inhibitory effect on pathogenic β-carbonic anhydrase enzymes especially compounds Vb, VIb and VIIb.
