Synthesis and Biological Evaluation of Novel Ciprofloxacin Derivatives

Abstract

Fluoroquinolones (FQs) were introduced in the late 1970s and constitute a major class of chemotherapeutics widely involved in the treatment of bacterial infections. They have gained global popularity due to their safety, easy tolerability, excellent pharmacokinetic properties, and high oral availability. Structural modifications of fluoroquinolones have resulted in new compounds possessing potent activity against various enzymes as well as cancer cell lines. Ciprofloxacin emerged in 1983 and has sustained four decades of clinical use globally. It proved as a major breakthrough in quinolone antibacterial therapy when used systematically (oral/injectable). In this thesis, five different series of ciprofloxacin based molecules have been synthesized such as ciprofloxacin based acetanilides (75a-j, 67-77% yield range), 1,3,4-oxadiazole hybrids of ciprofloxacin (86a-j, 65-87% yield range), carboxamide and sulfonamide derivatives of ciprofloxacin (85, 88, 89a-c and 91a, b, 66-87% overall yield range), ciprofloxacin based ꞵ-amino alcohols (94a-h, 70-85% yield range), and 1,2,4-triazole hybrids of ciprofloxacin (99a-e, 65-73% yield range). For this purpose, starting precursors such as a variety of substituted 2-bromo N-phenylacetamides, 1,3,4-oxadiazoles, 1,2,4-triazoles, and aryl glycidyl ethers were prepared and then they successfully coupled with ciprofloxacin ester and acetamide of ciprofloxacin. The biological potential of the synthesized derivatives was assessed using various assays such as anticancer, antibacterial and enzyme inhibition, etc. Anticancer activity was evaluated by using MCF-7, A549, Huh-7, and Hep G2 cancerous cells via MTT assay. Their bactericidal potency was assessed against B. subtilis and E. coli. In-vitro inhibition of acetylcholinesterase, butyrylcholinesterase, and serine proteases by ciprofloxacin derivatives was also determined.