Antiproliferative Activities of Lipophililic Fluoroquinolones-Based Scaffold Against a Panel of Solid and Liquid Cancer Cell Lines

Abstract

Objectives: In this work, 9 lipophilic-acid chelating FQs (fluoroquinolones) comprising chelating groups have been prepared, characterized and screened for in vitro cytotoxicity, radical scavenging and antiinflammation propensities. Methods: Using sulforhodamine B colorimetric bioassay vs. cisplatin; FQs-inflicted reductions’ of viability against breast T47D and MCF7, Pancreatic PANC-1, colorectal HT29, HCT116, SW620, CACO2, SW480 and Leukaemia K562 cancer cell lines were examined in quadruplicates/dose/cell line. Parameters including potency, toxicity, and selectivity (potency/toxicity) have been reported along with DPPH and NO-radicals’ scavenging capacities -as their molecular action mechanism-in comparison to ascorbic acid and indomethacin respectively. Using Griess assay in Lipopolysaccharide (LPS) prompted RAW264.7 macrophages; mitigation of inflammation was investigated. Results: nitroFQ 3b, unlike the rest of FQs in PANC1 and MCF7 cells, exhibited remarkably superior NO-radical scavenging/ antiinflammation capacity to indomethacin with respective antiproliferative IC50 values (<50μM) 49 vs. cisplatin’s 122 and 6 vs. cisplatin’s 28 (p<0.01-0.001; n=4). Reduced FQ 4b of significantly dual DPPH-NO scavenging propensities exerted exceptionally substantial micromolar antiproliferation in colorectal cancer cells with respective antiproliferative IC50 values (<50μM) of HCT116 0.84< HT29 1.6 <0.01-0.001; n=4). FQ 5a of superb NO radical reduction effect had antiproliferative IC50 value (<50μM) of 37.6 in PANC1 cells. In breast cancer T47D the ascending order of pronounced nano-micromolar antiproliferative IC50 values (<50μM) was 4d<3d<4a<4b<3b (0.009<0.59<10<15<41 vs. cisplatins’, p<0.01-0.001; n=4). Both 4d and 4b displayed both DPPHNO radicals reduction –related cytotoxicities. NO radical scavengers 3d and 3b as well as DPPH radical scavenger 4a exerted highly appreciably relevant antineoplastic affinities. Conclusion: Acidic groups and C8-C7 ethylene diamine Chelation Bridge along with bulky dual halogenations can be substantially associated with molecular action mechanisms of FQs cytotoxicities, antioxidative and antiinflammation effects, collectively.