Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent

Abstract

Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-positive and -negative bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa.Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.

Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

“…Aqueous solubility was determined in 96‐well plate format at pH 6.5 using the miniaturised shake‐flask method reported previously [54] . Briefly, a 10Mm stock of the sample was prepared in DMSO, from which 4 μL was aliquoted to a 96‐well plate and evaporated using a GeneVac system.…”

“…Aqueous solubility was determined in 96-well plate format at pH 6.5 using the miniaturised shake-flask method reported previously. [ 54 ] Briefly, a 10Mm stock of the sample was prepared in DMSO, from which 4 μL was aliquoted to a 96-well plate and evaporated using a GeneVac system. Phosphate buffer saline (pH 6.5) was then added to the compounds containing wells, and the plate incubation for 24 h at 25 °C while shaking.…”