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Updated: Jun 11, 2025
Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Evaluation of Quinoline-Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative,
Shereen Arabiyat1, Ahmad Alzoubi2, Hala Al-Daghistani2
1Al-Balqa Applied University, Salt, Jordan.
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.
Insights
This study found that quinoline derivatives and gemifloxacin exhibit potent anti-inflammatory and anti-cancer properties. These compounds show promise for drug repurposing, offering new therapeutic options with reduced side effects.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Rising cancer prevalence and treatment costs necessitate novel therapeutic strategies.
- Drug repurposing offers an efficient approach to developing new medications.
- There is a need for anti-inflammatory and anti-cancer agents with minimal side effects.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-cancer activities of quinoline derivatives.
- To evaluate the potential of these compounds for drug repurposing.
- To explore the structure-activity relationships of novel quinoline-based pharmacologies.
Main Methods:
- Assessed anti-inflammatory effects using lipopolysaccharide (LPS)-induced inflammation in RAW264.7 mouse macrophages.
- Determined anti-cancer activity via sulforhodamine B colorimetric assays against various cancer cell lines.
- Evaluated antioxidant capacity using the DPPH radical scavenging assay.
Main Results:
- Selected quinoline derivatives and gemifloxacin demonstrated significant anti-inflammatory effects without cytotoxicity.
- Gemifloxacin and several quinoline derivatives exhibited potent anti-proliferation activity against diverse cancer cell lines.
- Certain quinoline derivatives showed selective cytotoxicity against specific cancer cells, including MCF7 and HELA.
Conclusions:
- Quinoline derivatives possess a dual pharmacological profile, exhibiting both anti-inflammatory and cytotoxic properties.
- These compounds hold significant potential for drug repurposing in cancer therapy and inflammation management.
- Further structural modifications could enhance the therapeutic efficacy of these promising scaffolds.
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