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

Aims : 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. Materials and Methods : The utility of 1,3-diarylenones, aka chalcones, 3a - i and 8a - j as building blocks to construct the corresponding bis-pyrazoline derivatives 5aa-bh and 9ad-bj . Screening the antibacterial behavior of the novel bis-pyrazoline derivatives against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant S. aureus (VRSA) bacterial strains was investigated. Results : 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. Conclusions : 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).