Synthesis and biological evaluation of ciprofloxacin – 1,2,3-triazole hybrids as antitumor, antibacterial, and antioxidant agents

Abstract

Six novel ciprofloxacin-1,2,3-triazole hybrids (6a-f) were synthesized via click reaction, by reacting of methyl 1-cyclopropyl-6-fluoro-4-oxo-7-(4-(3-oxobutanoyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (5) with various aryl azides (9a-f). The new compounds were characterized using High-Resolution Mass Spectrometry (HRMS), 1H NMR, 13C NMR, and elemental analysis. Compounds (6a-f) screened for their in vitro anticancer activity against three cell lines, namely, non-small cell lung cancer (A549), glioblastoma (U-87 MG), and breast cancer (MCF7). Hybrids 6a and 6b exhibited remarkable anti-proliferative activity against all three cell-lines. IC50 values of 6b for all cancer cell lines were significantly lower comparing to the standard reference compound IC50. The IC50 of 6b for the normal cell (HDF) line was significantly higher than the reported for cisplatin [IC50 = 170.7 ± 8.1 μM/ml (HDF), (p ≤ 0.001)], indicating less toxicity towards normal cells and thereby has a better therapeutic index, with a selectivity index of 142.3 for U87 cell line. Compounds 6e, 6d, and 6f displayed significant cytotoxic activity against only U-87 and MCF-7 cancer cell lines, compared to normal cells (HDF). Compound 6f [IC50 = 7.9 ± 2.3 μM/ml (U-87) and 10.6 ± 3 μM/ml (MCF-7)] was more potent than cisplatin [IC50 = 28.3 ± 5.3 μM/ml (U-87) and 26.9 ± 4.7 μM/ml (MCF-7)] in displaying anti-proliferative effect against U-87 and MCF-7 cells, with less cytotoxic to normal cells [IC50 = 141.7 ± 4.1] than cisplatin [IC50 = 40.9 ± 5.4]. Moreover, they were tested for their antioxidant activity in DPPH and ABTS assays and antibacterial activity.