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.