Novel Lomefloxacin–Triazole Hybrids: Design, Synthesis and In Vitro Antiproliferative Activity in Breast, Melanoma and Colon Cancer Cell Lines

Abstract

In recent years, extensive research has focused on fluoroquinolone–triazole hybrids, with particular emphasis on structural modifications of ciprofloxacin. In the present study, novel derivatives of lomefloxacin with a 1,4-disubstituted-1,2,3-triazole moiety were designed, synthesised, and biologically evaluated at the N4 position of the piperazine ring. Molecular docking studies suggested potential interactions of the designed compounds with topoisomerase I, with docking scores comparable to that of the reference compound camptothecin. Molecular dynamics simulation suggested short-term conformational stability of the ligand-based (holo) topoisomerase IIβ modulator. The synthesis was accomplished using a copper(I)-catalysed azide–alkyne cycloaddition, leading to the formation of nine new compounds. A preliminary evaluation of antiproliferative activity was performed on selected human cancer cell lines using the WST-1 assay, while selectivity against normal human dermal fibroblast was assessed. The results obtained revealed promising antiproliferative activity of the tested derivatives, particularly against colorectal cancer cell lines.