Ciprofloxacin is a broad spectrum fluoroquinolone antibiotic that acts by the inhibition of bacterial topoisomerase type II (DNA gyrase) and have a potent activity against Gram positive and negative bacteria. However, due to its rigid and solid-state structure it suffers from limited water solubility. Improving its pharmacokinetic properties especially its water solubility is the concern of this work through the synthesis of various derivatives of ciprofloxacin with ethylene glycols through prodrug strategy without reducing its antibacterial activity. Shake-flask method was used to measure the aqueous solubility in phosphate buffer. The ciprofloxacin analogues were adequately stable at acidic and physiological pH. Synthesized derivatives were subjected to esterase-mediated hydrolysis reaction for the release of the drug from its prodrug form and showed a total hydrolysis after 25 min. Also antibacterial activity was studied against Staphylococcus aureus and Escherichia coli. Compared to ciprofloxacin, the solubility was increased for the three derivatives, and the antimicrobial activity was enhanced up to 40%.