SYNTHESIS, CHARACTERIZATION AND EVALUATION OF 4-HYDROXY-1-PHENYL/METHYL-3-(3-SUBSTITUTED-1-(SUBSTITUTEDIMINO) PROPYL) QUINOLINE-2(1H)-ONE DERIVATIVES AND 4-HYDROXY-1-PHENYL/METHYL-3-(1-(SUBSTITUEDIMINO) ETHYL) QUINOLINE-2(1H)-ONE DERIVATIVES AS POSSIBLE ANTICANCER AGENTS
DOI:
https://doi.org/10.22159/ijpps.2017v9i10.20184Keywords:
Linomide, Quinolin-2-one, Anticancer, MTT assayAbstract
Objective: Synthesis, characterization and evaluation of quinolin-2-one derivatives as possible anticancer agents.
Methods: A series of novel 4-hydroxy-1-phenyl/methyl-3-(3-substituted-1-(substitutedimino)propyl)quinolin-2(1H)-one derivatives IIa(1-5)/IIb(1-5) and 4-hydroxy-1-phenyl/methyl-3-(1-(substituedimino)ethyl)quinolin-2(1H)-one derivatives IIIa(1-3)/IIIb(1-3) were synthesised by nucleophilic addition of substituted anilines on 3-acetyl-4-hydroxy-1-phenyl/methylquinolin-2(1H)-one (a/b) and 4-hydroxy-3-(3-substitutedpropanoyl)-1-phenyl/methyl quinolin-2(1H)-one (Ia/Ib); respectively. The synthesised derivatives were characterised by spectral analysis and were tested for their in vitro anticancer activity against K562 and Hep 3b cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method.
Results: The compounds were tested for their in vitro anticancer activity against K562 and Hep 3b cell lines at 10, 20, 25, 30 and 50 µg/ml concentration using MTT assay method. The compound 4-hydroxy-3-(3-morpholino-1-(phenylimino)propyl)-1-phenylquinolin-2(1H)-one (IIa-1) showed anticancer activity with IC50 value 20 µg as compared to the control against K562 cell lines. The compound 4-hydroxy-1-phenyl-3-(1-(phenylimino) ethyl) quinolin-2(1H)-one (IIIa-1) showed anticancer activity with IC50 value less than 10 µg.
Conclusion: The proposed method for the synthesis of novel derivatives is convenient and gives a good yield. Some of the synthesised compounds showed promising anticancer activity against K562 and Hep 3b cell lines. Compound IIa-1 (R=-C6H5; R1= morpholine; R2= C6H5-NH-) exhibited most potent activity against K562 cell lines. Compound IIIa-1 (R=-C6H5; R3= C6H5-NH-) has been proved to be the most cytotoxic compound among the other derivatives against Hep 3b cell lines.
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References
www.who.int/media centre/factsheets/fs297/en. [Last accessed on 15 Mar 2017]
Thomas K. The pyrano route to 4-hydroxy-2-quinolones and 4-hydroxy-2-pyridones. IL Farmacol 1999;54:309-15.
Afzal O, Kumar S, Haidar R, Ali R, Kumar R, Jaggi M, et al. A review on anticancer potential of bioactive heterocycle quinoline. Eur J Med Chem 2015;97:871-910.
Ohashi T, Oguro Y, Tanaka T, Shiokawa Z, Shibata S, Sato Y, et al. Discovery of pyrrolo[3,2-c]quinolin-4-one derivatives as novel hedgehog signalling inhibitors. Bioorg Med Chem 2012;20:5496.
Zhang Q, Chen Y, Zheng YQ, Xia P, Xia Y, Yang ZY, et al. Synthesis and bioactivity of 4,10-dimethylpyridino[2,3-h]quinolin-2(1H)-one-9-carboxylic acid and its esters. Bioorg Med Chem 2003;11:1031.
Maria GR, Shivlingrao MD, Soniya N, Jairus F, Prasad T, et al. Synthesis and evaluation of 2-(4-methoxy-2-oxo-1-phenyl/ methyl-1,2-dihydroquinolin-3-yl)-2-methyl-3-(phenyl/ substitutedphenylamino)thiazolidin-4-one as antibacterial and anticancer agents. Indian J Chem 2016; 55B:1254-8.
Trianquand C, Romanet JP, Nordmann JP, Allaire C. Efficacy and safety of long-acting carteolol 1% once daily. A double-masked, randomised study. J Fr Opthalmol 2003;26:131-6.
Ogino K, Hobara T, Ishiyama H, Yamasaki K, Kobayashi H, Izumi Y, et al. Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats. Eur J Pharmacol 1992;212:9-13.
De Fruyt J, Deschepper E, Audenaert K, Constant E, Floris M, Pitchot W, et al. Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. J Psychopharmacol 2012;26:603-17.
Qun L, Keith WW, Weibo W, Nan-Horng L, Akiyo C, Wen-zhen G, et al. Design, synthesis and activity of achiral analogues of 2-quinolones and indoles as non-thiol farnesyltransferase inhibitors. Bioorg Med Chem Lett 2005;15:2033-9.
Jiangdong S, Zili X, Michael AI, Chandrashekhar K, Bulbul P, Zhigen H, et al. Structure-activity relationships studies of the anti-angiogenic activities of linomide. Bioorg Med Chem Lett 2003;13:1187-9.
Jochmans D. Novel HIV-1 reverse transcriptase inhibitors. Virus Res 2008;134:171-85.
Khan SR, Mhaka A, Pili R, Issacs JT. Synthesis and antiangiogenic activity of linomide. Bioorg Med Chem Lett 2001;11:451-2.
Roschger P, Fiala W, Stadlbaurer W. Nucleophilic substitution and ring closure reactions of 4-chloro-3-nitro-2-quinolones. J Heterocyclic Chem 1992;29:225.
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