Novel Quinolone Substituted Quinazolin-4(3H)-Ones as Anti-Inflammatory, Anticancer Agents: Synthesis and Biological Screening
Santosh Kumar1, Jignesh Chhaganbhai Aghara1, Angel Treasa Alex2, Jesil Mathew Aranjani2, Alex Joesph1★★ Corresponding author
- 1Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal-576104, Karnataka, INDIA.
- 2Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal-576104, Karnataka, INDIA.
CORRESPONDENCE
Alex Joesph
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal-576104, Karnataka, INDIA.
Received: 29-01-2018; Revised: 17-05-2018; Accepted: 22-05-2018.
Volume 52, Issue 4S · pp. s268–s276 · PUBLISHED 2018 · DOI: 10.5530/ijper.52.4s.107
ABSTRACT
Background: Quinolones and, quinazolinones are important pharmacodynamic heterocyclic nuclei which when incorporated into different heterocyclic templates, have been reported to possess potent anti-inflammatory and anticancer properties. The activity of these compounds were associated with inhibition of nuclear factorkappaB (NF-κB) which is one of the important targets studied for designing of antiinflammatory and antitumor drug. Further, the combination of two pharmacophores on the same molecule is a well-established approach for designing of potent molecules and may further enhance their activity. Objectives: Aim of the study is to synthesis a series of quinolone substituted quinazolinones and evaluation of their anti-inflammatory and anticancer activity. Methods: Quinolone substituted quinazolin-4(3H)-ones were synthesized in two steps, first step involves synthesis of 7-amino-4-methyl-quinolin2(1H)-one. Second step involves aminolysis of 7-amino-4-methyl-quinoline-2(1H)-one with substituted benzoxazines afforded quinolone substituted quinazolinones. Structures of synthesized compounds were characterized by spectral techniques. The synthesized compounds were evaluated for anti-inflammatory activity by carrageenan-induced rat paw oedema test and anticancer activity was assessed by evaluating the cytotoxic effect of synthesized compounds on BT-549 and HeLa, human cancer cell lines by MTT assay. Results: The synthesized compounds; 6, 7-dimethoxy-2-methyl-3-(4-methyl2-oxo-1, 2-dihydroquinolin-7-yl)quinazolin-4(3H)-one (6d) was the most cytotoxic compound against HeLa and BT-549 human cancer cell lines. While the compounds 6,8-dibromo-2-methyl-3-(4-methyl-2-oxo-1,2-dihydroquinolin-7-yl)quinazolin-4(3H)-one (6f) and 2-methyl-3-(4-methyl-2-oxo-1,2-dihydroquinolin-7-yl)-7-nitroquinazolin-4(3H)- one (6g) exhibited the highest anti-inflammatory activity in carrageenan-induced paw oedema model. Conclusion: Molecular docking studies revealed that combination of two pharmacophores was crucial for binding of quinolone substituted quinazolin-4(3H)-ones on NF-κB and good correlation was observed between docking scores and biological activity of synthesized compounds.
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Kumar, S., Aghara, J. C., Alex, A. T., Aranjani, J. M., & Joesph, A. (2018). Novel Quinolone Substituted Quinazolin-4(3H)-Ones as Anti-Inflammatory, Anticancer Agents: Synthesis and Biological Screening. Indian Journal of Pharmaceutical Education and Research, 52(4S), s268–s276. https://doi.org/10.5530/ijper.52.4s.107