SYNTHESIS OF 4-HYDROXY-3-(1-HYDROXY-2-(SUBSTITUTEDAMINO)ETHYL)-1-PHENYL/ METHYL QUINOLIN-2(1H)-ONE AS ANTICANCER AGENTS
Â Objective: The current work is concerned with the synthesis of a series of 4-hydroxy-3-(1-hydroxy-2-(substituted amino)ethyl)-1-phenyl/ methylquinolin-2(1H)-one[III-a(1-5)/III-b(1-5)] and evaluation of its in vitro anticancer activity.
Methods: The starting material for linomide analogs was synthesized by following literature procedures. The carbonyl group was reduced to hydroxyl group using sodium borohydride, and the methyl group was brominated using bromine in acetic acid. Further bromine was nucleophilically substituted by primary amines. All the synthesized compounds were satisfactorily characterized by infrared, nuclear magnetic resonance, and mass spectral data. The synthesized compounds were tested for in vitro anticancer activity against MDA-MB cell line using the MTT assay method.
Results: Among all the synthesized compounds, compound [III-a1;R=C6H5,R1=n-propylamine], [III-b1;R=CH3,R1=n-propylamine], and [III-b2;R=CH3,R1=methylamine] were found to be most cytotoxic with IC50 value=25 Î¼g against the MDA-MB cell line.
Conclusion: The results of screening studies concluded that compounds with (C6H5 at C1) and (long chain aliphatic and cyclic amines at C3) position of quinolin-2-one ring showed moderate activity.
2. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med 2002;53:615-27.
3. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. Lancet Oncol 2012;13(6):607-15.
4. Sravanthi TV, Rani S, Manju S. Synthesis and biological evaluation of 2-(2â€™/3â€™/4â€™/6â€™-substitutedphenyl)-1H-indoles. Int J Pharm Pharm Sci 2015;7(11):268-73.
5. Ahmed SM, Mohamed E, Sanaa ME. 2,4-cycloaddition reactions: Preparation and cytotoxicity of novel quinoline and pyrrolo-[3,4-f]-quinoline derivatives. Int J Pharm Pharm Sci 2015;7(12):64-8.
6. Abbas P, Alizera F, Mehdi H, Saeed R. In-vitro cytotoxicity and phototoxicity of N-piperzinyl quinolone derivatives with a 2-thienyl group. Toxicol In Vitro 2007;21:1031.
7. Chen YL, Chung CH, Chen IL, Chen PH, Jeng HY. Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives. Bioorg Med Chem 2002;10(8):2705-12.
8. George CP, Elizabeth MJ. Cancer Immunotherapy. 2nd ed. San Diego, CA: Academic Press; 2012.
9. Anisha R, Shivalingrao M, Soniya N, Prassad T. Synthesis of 4-methoxy-1-phenyl/methyl-3-[5-(phenyl/substitutedphenyl)-,5-dihydro-(1H)-one derivatives as a antibacterial agents. Indian J Heterocyclic Chem 2015;25:173.
10. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65(1-2):55-63.
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