Design, synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity

Hamada H H Mohammed; El-Shimaa M N Abdelhafez; Samar H Abbas; Gamal A I Moustafa; Glenn Hauk; James M Berger; Satoshi Mitarai; Masayoshi Arai; Rehab M Abd El-Baky; Gamal El-Din A Abuo-Rahma

doi:10.1016/j.bioorg.2019.102952

Design, synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity

Bioorg Chem. 2019 Jul:88:102952. doi: 10.1016/j.bioorg.2019.102952. Epub 2019 Apr 25.

Affiliations

¹ Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New-Minia 61519, Egypt.
² Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
³ Deprtment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Bacteriology Division, Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose 204-8533, Japan.
⁵ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁶ Department of Microbiology & Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁷ Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Electronic address: gamal.aborahma@mu.edu.eg.

PMID: 31039471
DOI: 10.1016/j.bioorg.2019.102952

Abstract

New N-4-piperazinyl ciprofloxacin-triazole hybrids 6a-o were prepared and characterized. The in vitro antimycobacterial activity revealed that compound 6a experienced promising antimycobacterial activity against Mycobactrium smegmatis compared with the reference isoniazide (INH). Additionally, compound 6a exhibited broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative bacteria compared with the reference ciprofloxacin. Also, compounds 6g and 6i displayed considerable antifungal activity compared with the reference ketoconazole. DNA cleavage assay of the highly active compounds 6c and 6h showed a good correlation between the Mycobactrium cleaved DNA gyrase assay and their in vitro antimycobactrial activity. Moreover, molecular modeling studies were done for the designed ciprofloxacin derivatives to predict their binding modes towards Topoisomerase II enzyme (PDB: 5bs8).

Keywords: Antibacterial; Antifungal; Antimycobacterial; Ciprofloxacin; DNA cleavage assay; Molecular docking.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Ciprofloxacin / chemistry
Ciprofloxacin / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Microbial Sensitivity Tests
Molecular Docking Simulation*
Molecular Structure
Mycobacterium / drug effects*
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Anti-Bacterial Agents
Triazoles
Ciprofloxacin

Grants and funding

R01 CA077373/CA/NCI NIH HHS/United States