One-Pot Synthesis of 5-(Het)Aryl 8-Aminoquinoline Amide Derivatives as Potential Antibacterial / Cytotoxic Agents

Author(s): Zanjam Spandana, Tadigiri M. Rekha, Mandava V.B. Rao*, Manojit Pal*

Journal Name: Current Bioactive Compounds

Volume 16 , Issue 2 , 2020

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Graphical Abstract:


Background: The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Dehydrogenase (G6PD) Activity. The 4-aryl- 8-amino(acetamido)quinoline derivatives, on the other hand, have shown antiproliferative activities against cancer cell lines. These reports prompted us to assess the antibacterial and cytotoxic activities of a series of compounds based on 5-aryl 8-aminoquinoline amide scaffold.

Methods: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized via a one-pot ultrasound-assisted method using a C-5 selective halogenation of quinoline derivatives followed by Pd/C-catalyzed Suzuki-Miyaura coupling with (het)aryl boronic acids. All these compounds were evaluated for their in vitro antibacterial activities against representative Gram-(+) and Gram-(-) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Staphylococcus aureus. Three compounds were further tested for cytotoxicities in vitro against breast adenocarcinoma (MCF7) and Hepatocellular Carcinoma (HepG2) along with non-cancerous human embryonic kidney (HEK293) cell lines.

Results: All these compounds demonstrated moderate to good antibacterial activities against the four organisms used. In vitro assay results revealed that three compounds showed good activities against Gram-(+) strains and Gram-(-) strains and one was comparable to ciprofloxacin and pefloxacin. These three compounds were further tested for their cytotoxic properties against MCF7 and HepG2 cell lines. One of them showed IC50 value comparable to doxorubicin when tested against HepG2 cell lines. However, none of these compounds showed any significant effects when tested against HEK293 cells indicating their selectivity towards the growth inhibition of cancer cells.

Conclusion: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized and evaluated for antibacterial and cytotoxic activities. Several of these compounds showed promising antibacterial and cytotoxic activities when tested in vitro suggesting that the present class of compounds may be of interest for the identification of new and potential antibacterial / cytotoxic agents.

Keywords: Quinolone, suzuki-miyaura coupling, Pd/C, antibacterial activity, cytotoxicity, methemoglobinemia.

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Article Details

Year: 2020
Published on: 22 April, 2020
Page: [142 - 151]
Pages: 10
DOI: 10.2174/1573407214666180910130225
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