Synthesis, spectroscopic characterization, antimicrobial activity, and computational studies of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety

• Published in: Journal of molecular structure 2025-02, Vol.1322, p.140456, Article 140456
• Main Authors: Reheim, Mohamed A.M. Abdel, Hafiz, Ibrahim S. Abdel, Reffat, Hala M., Rady, Hend S. Abdel, Abdelmonsef, Aboubakr H.
• Format: Article
• Language: English
• Subjects: ADMET analysis; Antimicrobial activity; Carboxylic acid hydrazide; DFT calculations; Molecular docking; Thienopyrazole
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.140456

•A new series of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety 2–13 was synthesized.•The newly synthesized compounds were identified in the basis of melting point, elemental analyses, and spectroscopic techniques.•The new compounds 2–13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains.•Molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA).•The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT.•The compounds 9 and 11 demonstrated impressive antimicrobial activity and exhibited good ADMET profile. A new series of thienopyrazoles linked to five and/or six heterocyclic nitrogen rings such as pyrazole, triazole-3-thione, oxadiazole, thiazole-2-thione and/or pyrimidone moieties was synthesized starting from 5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6-carboxylic acid hydrazide as a key precursor. For the synthesis of new thienopyrazoles 2–13, the carboxylic acid hydrazide derivative 1 served as a crucial intermediary. These novel heterocyclic structures were confirmed by analytical and spectroscopic methods (m.p., IR, 1H NMR, 13C NMR, and MS). The new compounds 2–13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains. Against numerous bacterial and fungal strains, certain derivatives of the produced compounds 9 and 11 demonstrated impressive antimicrobial activity. Besides, molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA) (2 × 3f.pdb). Among the series, compounds 9 and 11 exhibited the best binding affinity towards the target enzyme -10.1 and -10.5 kcal/mol, respectively. The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT (Density Functional Theory) analysis. Our findings represented that both derivatives 9 and 11 could be utilized for development antimicrobial drug candidates.