Two Novel Regioisomeric Series of Bis-pyrazolines: Synthesis, <i>In Silico</i> Study, DFT Calculations, and Comparative Antibacterial Potency Profile against Drug-Resistant Bacteria; MSSA, MRSA, and VRSA

Abstract

<i>Aims</i>: Design and synthesis of antimicrobial prototypes that are capable of eradicating bacterial biofilm formation that is responsible for many health challenges particularly with antibiotic-resistant bacterial species. <i>Materials and Methods</i>: The utility of 1,3-diarylenones, <i>aka</i> chalcones, <b>3a</b>-<b>i</b> and <b>8a</b>-<b>j</b> as building blocks to construct the corresponding bis-pyrazoline derivatives <b>5aa-bh</b> and <b>9ad-bj</b>. Screening the antibacterial behavior of the novel bis-pyrazoline derivatives against methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA), methicillin-resistant <i>S. aureus</i> (MRSA), and vancomycin-resistant <i>S. aureus</i> (VRSA) bacterial strains was investigated. <i>Results</i>: Chalcones were used as building scaffolds to construct two series of di- and trisubstituted bis-pyrazoline derivatives. Numerous novel bis-compounds displayed decent bacterial biofilm suppression. <i>Conclusions</i>: Two regioisomeric series of bis-chalcones were designed and constructed, and their structural diversity was manipulated to access the intrinsically bioactive, pyrazoline ring. The newly synthesized bis-pyrazoline derivatives presented decent antibacterial behavior against multiple drug-resistant bacterial strands (MSSA, MRSA, and VRSA).