Synthesis, <i>in vitro</i> -antimicrobial investigation, molecular docking, and DFT studies of novel bis-thiazole derivatives

Two series of bis-thiazole derivatives (7a–f and 9a–j) were synthesized efficiently via two steps. First, the condensation of 3,3'-(alkane-diylbis(oxy)) dibenzaldehyde (3a,b) with hydrazinecarbothioamide (4) affording 2,2'-(((alkane-1,2-diylbis(oxy))bis(3,1-phenylene))bis(methaneylylidene))bis(hydrazine-1-carbothioamide) (5a,b). The formed 5a,b were then mixed with 2-bromo-1-arylethan-1-one 6a–c affording the corresponding thiazole derivatives 7a–f. Similarly, bis-thiazole derivatives 9a–j were synthesized through heating bis(hydrazine-1-carbothioamides) 5a,b with 2-oxo-N-arylpropanehydrazonoyl chloride 8a–i. Afterwards the synthesized bis-thiazoles 7a–f and 9a–j were evaluated for their in vitro-antibacterial activity against gram-positive and gram-negative bacterial strains. Among the tested candidates, compounds 7a, 7c, and 7d exhibited the highest antibacterial activity. Furthermore, a docking analysis showed that the most promising biologically active candidates under investigation are joined to the same amino acid (acids) as references supporting the biological activity of the tested compounds toward both gram-positive bacteria-protein and gram-negative bacteria-protein. DFT calculations were carried out to gain a better understanding of the target bis-thiazole-structures and their assembly mechanism.