Abstract
A series of new antipyrine incorporated thiazole derivatives having phenoxyacetamide moiety as a link bridge was synthesized. The synthetic strategy involves condensation of the precursor N-(4-antipyrinyl)-2-(4-formylphenoxy)acetamide with thiosemicarbazide followed by heterocyclization of the produced thiosemicarbazone with various α-halogenated carbonyl compounds (namely; 4-chlorophenacyl bromide, ethyl bromoacetate, 3-chloroacetylacetone and ethyl 4-chloroacetoacetate). Moreover, the quantum chemical calculations at DFT/B3LYP level were used to determine the HOMO-LUMO energies and Fukui’s indices toward nucleophilic, electrophilic and radical attacks. The investigated compounds were arranged due to HOMO-LUMO energy gap as following 6 < 5 < 7 < 3 < 2 < 4 < 8. The synthesized antipyrinyl-thiazole hybrids were screened to evaluate their antibacterial and antifungal efficacies. Using Chloramphenicol as reference material, the synthesized antipyrinyl-thiazole hybrids were revealed a remarkable activity against S. aureus than B. subtilis, as example for Gram’s positive strains. The antipyrine-thiazole compounds 3, 4, 6 and 8 exhibited significant MIC values. However, the antipyrine-thiazole hybride 4 displayed reputable activities against Gram’s negative strains S. typhimurium and E. coli, respectively, in comparison with Cephalothin. Likewise, the compounds 7 and 8 were demonstrated respectable antifungal efficacy toward C. albicans in contrast to cycloheximide grade. The theoretical molecular docking studies were applied to simulate reactivity of the synthesized antipyrine-thiazole hybrids against contrasting binding sites for both of Staphylococcus aureus “Homo sapiens” (pdb: 3HUN) protein and E.coli “Homo sapiens” (PDB: 2EXB) protein. The theoretical and practical antibacterial and antifungal activities result in this work designated a proper agreement.