Synthesis, Antimicrobial Activity and Molecular Docking of Novel Series of Phthalazine Derivatives

Rezk, Marwa M.; Wasfy, A. A. F.; Behalo, Mohamed S.; El-kalyoubi, Samar; Aly, Aly A.

doi:10.21608/ejchem.2025.361774.11447

Synthesis, Antimicrobial Activity and Molecular Docking of Novel Series of Phthalazine Derivatives

Articles in Press

Document Type : Original Article

Authors

¹ Benha University, Faculty of Science, Chemistry Department, Egypt

² Port Said University, Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Egypt

³ Chemistry Department, Faculty of Science, Benha University, Benha, Egypt

10.21608/ejchem.2025.361774.11447

Abstract

A straightforward and effective method for synthesizing phthalazine derivatives was developed through the reaction of 1-(4-(4-chlorophthalazin-1-yl)phenyl]-pyrrolidine-2,5-dione (3), a key precursor, with various nucleophiles containing carbon, nitrogen, oxygen, and sulfur. The structures of all synthesized compounds were verified through elemental analysis and spectral data. Furthermore, certain derivatives were assessed for their antibacterial and antifungal activities and compared with standard drugs. Among them, compounds 4, 14a, 15, and 18 demonstrated antimicrobial activity, positioning them as promising candidates for therapeutic use. In vitro testing demonstrated their potent efficacy against bacterial strains (Escherichia Coli, Staphylococcus Aureus) and fungal pathogens (Aspergillus niger), indicating broad-spectrum antimicrobial potential. Molecular docking analyses supported these findings, revealing strong binding interactions with key microbial enzymes, which aligns with their observed inhibitory effects. Combining potent antimicrobial activity and favorable pharmacokinetic characteristics, these compounds emerge as promising leads for the development of multitarget drugs targeting infectious diseases.

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