Evaluation of Quinoline-Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative, Antioxidative, and Anti-Inflammatory Agents

Abstract

The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half-maximal inhibitory concentration (IC₅₀ value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline-4-carboxlic and quinoline-3-carboxylic acids) exerted impressively appreciable anti-inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline-2-carboxylic acid, quinoline-4-carboxylic acid, quinoline-3-carboxylic acid, and 1,2-dihydro-2-oxo-4-quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline-2-carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co-planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti-inflammation pharmacologies of quinoline derivatives. Activity-guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.