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

Refaie M Kassab; Magdi E A Zaki; Sami A Al-Hussain; Aboubakr H Abdelmonsef; Zeinab A Muhammad

doi:10.1021/acsomega.3c06348

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

ACS Omega. 2024 Jan 9;9(3):3349-3362. doi: 10.1021/acsomega.3c06348. eCollection 2024 Jan 23.

Authors

Refaie M Kassab¹, Magdi E A Zaki², Sami A Al-Hussain², Aboubakr H Abdelmonsef³, Zeinab A Muhammad⁴

Affiliations

¹ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
² Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
³ Chemistry Department, Faculty of Science, South Valley University, Qena 83523, Egypt.
⁴ Pharmaceutical Chemistry Department, National Organization for Drug Control and Research (NODCAR), Giza 12311, Egypt.

Abstract

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).