title: Design, synthesis, molecular docking, anti-Proteus mirabilis and urease inhibition of new fluoroquinolone carboxylic acid derivatives.
abstract: New hydroxamic acid, hydrazide and amide derivatives of ciprofloxacin in addition to their analogues of levofloxacin were prepared and identified by different spectroscopic techniques. Some of the prepared compounds revealed good activity against the urease splitting bacteria, Proteus mirabilis. The urease inhibitory activity was investigated using indophenol method. Most of the tested compounds showed better activity than the reference acetohydroxamic acid (AHA). The ciprofloxacin hydrazide derivative 3a and levofloxacin hydroxamic acid 7 experienced the highest activity (IC50=1.22μM and 2.20μM, respectively). Molecular docking study revealed high spontaneous binding ability of the tested compounds to the active site of urease.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Mohammed A A
authors.initials: MA
authors.lastname: Abdullah
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Electronic address: gamal.aborahama@mu.edu.eg.
authors.forename: Gamal El-Din A A
authors.initials: GE
authors.lastname: Abuo-Rahma
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: El-Shimaa M N
authors.initials: EM
authors.lastname: Abdelhafez
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Heba A
authors.initials: HA
authors.lastname: Hassan
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
authors.forename: Rehab M
authors.initials: RM
authors.lastname: Abd El-Baky
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D055808:Drug Discovery; D024841:Fluoroquinolones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011512:Proteus Infections / Q000188:drug therapy / Q000382:microbiology; D011513:Proteus mirabilis / Q000187:drug effects / Q000201:enzymology*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D006877:Hydroxamic Acids; C006358:acetohydroxamic acid; D014510:Urease
keywords: Antibacterial; Docking; Fluoroquinolones; Hydroxamic acid; Urease inhibitors