A SAR Study: Evaluation of Bromo Derivatives of 8-Substituted Quinolines as Novel Anticancer Agents

Title:A SAR Study: Evaluation of Bromo Derivatives of 8-Substituted Quinolines as Novel Anticancer Agents

Volume: 14 Issue: 12

Author(s): Salih Okten*, Osman Cakmak, Saban Tekin and Tugba Kul Koprulu

Affiliation:

• Department of Maths and Science Education, Division of Science Education, Faculty of Education, Kirikkale University, 71450, Yahsihan, Kirikkale,Turkey

Keywords: SAR, bromination, hydroxyquinoline, methoxyquinoline, cyanoquinoline, anticancer effect, cytotoxicity, antitopoisomerase.

Abstract: Background: Brominated 8-hydroxy, 8-methoxy, 8-amino quinolines 5, 6, 8, 9 and novel cyano 8-hydroxyquinolines 11, 12 were evaluated in vitro for their anticancer effects on various cell lines. 5,7-Dibromo- 5, 7-bromo- 6, 7-cyano- 11 and 5,7-dicyano-12 8-hydroxyquinolines were shown to have strong antiproliferative activity against various tumor cell lines, including C6 (rat brain tumor), HeLa (human cervix carcinoma), and HT29 (human colon carcinoma) with IC50 values ranged from 6.7 to 25.6 µg/mL.

Methods: A structure activity relationship (SAR) was conducted that quinoline core containing hydroxly group at C-8 positon led to more anti cancer potentials.

Results: The results of Lactate Dehydrogenase (LDH) cytotoxic, DNA laddering and inhibition assays indicated that 5, 6, 11 and 12 have high cytotoxic effects and appototic potentials.

Conclusion: Furthermore, 5 and 12 have inhibitory effects on relaxation of supercoiled plazmid DNA by supressed the Topoisomerase I enzyme. As a result, 5, 6, 11 and 12 may have promising anticancer drug potential and 5 and 12 may be novel topoisomerase inhibitors.

Cite this article as:

Okten Salih *, Cakmak Osman , Tekin Saban and Koprulu Kul Tugba , A SAR Study: Evaluation of Bromo Derivatives of 8-Substituted Quinolines as Novel Anticancer Agents, Letters in Drug Design & Discovery 2017; 14 (12) . https://dx.doi.org/10.2174/1570180814666170504150050