Exploration of Spirocyclic Derivatives of Ciprofloxacin as Antibacterial Agents
Alexei Lukin, М. В. Чудинов, Tatiana Vedekhina, Elizaveta Rogacheva, Л. А. Краева, Olga Bakulina, Mikhail Krasavin
Abstract
The previously reported as well as newly synthesized derivatives of the 1-oxa-9-azaspiro[5.5]undecane were employed in the synthesis of thirty-six derivatives of ciprofloxacin using commercially available 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and the literature protocol involving the preparation of boron chelate complex to facilitate nucleophilic aromatic substitution. All new fluoroquinolone derivatives were tested against two gram-positive as well as three gram-negative strains of bacteria. With the activity spectrum of the new derivatives being substantially narrower than that of ciprofloxacin, compounds were distinctly active against two of the five strains: gram-negative Acinetobacter baumannii 987® and gram-positive Bacillus cereus 138®. Towards these two strains, a large group of compounds displayed equal or higher potency than ciprofloxacin.