In vitro Antiproliferative Properties of Lipophililic -Acid Chelating Fluoroquinolones and triazoloFluoroquinolones with 7-dihaloanilinosubstitution

Background Incidence rates and prevalence of cancer are substantially high globally. New safe therapeutic drugs are endorsed to overcome high toxicity and poor safety profile of clinical anticancer agents. Objectives As antineoplastic Vosaroxin is a commercial fluoroquinolone (FQ); we hypothesize that superlative antiproliferation activity of lipophilic FQs/TFQs series correlate to their acidic groups and C8-C7 ethylene diamine Chelation Bridge along with bulky dual halogenations. Methods we tested dual lipophilic- acidic chelating FQs with a genuine potential of antiproliferative propensities based to their dual DPPH- and NO- radicals scavenging biocapacities using cell based - and colorimetric assays vs. respective reference agents as their molecular action mechanism. Results In this work, 9 lipophilic-acid chelating FQs and their cyclized TriazoloFQs (TFQs) designed to bear 7-dihaloanilino substituents with special focus on dichlorosubstitutions have been prepared, characterized and screened against breast T47D and MCF7, Pancreatic PANC-1, colorectal HT29, cervical HELA, lung A375, skin A549 and Leukaemia K562 cancer cell lines using sulforhodamine B colorimetric bioassay. Parameters including potency, toxicity, and selectivity (potency/toxicity) have been reported along with DPPH- and NO- radicals' scavenging propensities -as their molecular action mechanism- in comparison to ascorbic acid and indomethacin respectively. Using Griess assay in lipopolysaccharide (LPS) prompted RAW264.7 macrophages inflammation, IC50 values (µM) in the ascending order of new FQs' NO scavenging/antiinflammation capacity were 4a<3a<4c