Synthesis, spectroscopic characterization, and antimicrobial evaluation of new aminochalcone salicylaldehyde Schiff bases

Antimicrobial resistance (AMR) is an escalating danger that threatens the global population. World Health Organization publishes regularly updates to highlight the risks. Therefore, the urgent need to discover new therapies is an everlasting challenge. Molecular hybridization of known chemical entities with established antimicrobial efficacy is one of the strategies to combat AMR. In this study, a new scaffold that combines a chalcone moiety with a salicylaldehyde derivative through a Schiff base linker was designed. The chalcone part was synthesized staring from 4-aminoacetophenone and either furfural or 2-thiophenecarbaldehyde affording furan-chalcone (FC) or thiophene-chalcone (TC), respectively. Subsequently, the Schiff bases were obtained upon reaction of the FC/TC with a salicylaldehyde derivative. 8 New Schiff bases (FCS/TCS) were synthesized and characterized by 1 H, 13 C NMR, IR, and mass spectroscopy. Consequently, the antimicrobial activities of the Schiff bases were evaluated. Notably, several derivatives showed activity against Gram-positive bacteria (MRSA and S. aureus ), with FCS2 and TCS2 having inhibition zones of 24 and 27 mm for MRSA; 23 and 24 mm for S. aureus , respectively. Vancomycin, the reference drug, had inhibition zones of 25 and 27 mm for MRSA and S. aureus , respectively. On the contrary, almost all derivatives lacked activity against Gram-negative bacteria ( E. coli and P. aeruginosa ). 3 derivatives (FCS2, TCS2, and TCS4) had an MIC value of 3.125mM against MRSA, while TCS2 and FCS1 had the same MIC against S. aureus . The MIC of vancomycin was 0.019 mM against MRSA and 0.009 mM against S. aureus. Furthermore, 5 derivatives exhibited noticeable antifungal activity against C. albicans , with TCS2 producing the largest inhibition zone of 29 mm, comparable to that of the standard antifungal agent fluconazole. While the MIC for fluconazole was 0.039 mM, the lowest MIC against C. albicans was 1.5625 mM, attained by TCS4 and FCS4.