Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents

• A series of triazole-bithiazole conjugates 4 , 5 , 8 , and 9 were synthesized. • The DFT/B3LYP modelling of the triazole-bithiazole conjugates implied twisted structures. • The triazole-bithiazole conjugate 9b presented the minimum energy of FMO’s gap. • The antibacterial effectiveness was established against several pathogens; bacterial and fungal strains. • The pharmacokinetic properties were assigned using the Swiss ADME tool. A series of new triazole-bithiazole conjugates were synthesized through a sequence of reactions started by chloroacetylation of 2-amino-4-triazolyl-thiazole compound 2 . The various spectroscopic techniques, such as IR, NMR and MS, confirmed the suggested chemical structure of isolated hybrids. The DFT studies of the produced derivatives revealed twisted configuration except for the parent 2 , how was planar. In addition, the researched conjugates presented extended FMO’s energy gap (ΔE H-L ) from 2.60 to 4.64 eV and could be sorted as 5b < 9b < 5a < 9a < 4 < 8 < 2 < 7 < 3 . The antibacterial and antifungal activity of the newly synthesized conjugates has been examined using the minimum inhibitory concentration (MIC) method against representative pathogens. The data revealed that conjugates 9a and 9b exhibited significant activity, compared to standard antimicrobial agents, ampicillin, and fluconazole. Moreover, the DNA gyrase enzyme inhibitory action of the synthesized triazole-bithiazoles was assessed and compared to novobiocin (Novo) as a standard inhibitor. Furthermore, the interaction of the synthesized conjugates with the amino acid residues of a target protein has been empathized via docking study, which cleared that conjugate 9b has the greatest binding affinity among the produced conjugates, showing its potential as an antibacterial agent. Finally, the pharmacokinetic properties of synthesized hybrids were ascribed using the SwissADME indicating good bioavailability for conjugates 3 , 4 , and 7 , while others, including 5a , 5b , 8 , 9a , and 9b , faced challenges related to low GI absorption and Lipinski violations.