Synthesis, Cytotoxic Evaluation, and Molecular Docking Studies of N-(7- hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide Analogues

Author(s): Mohamed Jawed Ahsan*, Rupesh Kumar Kumawat, Surender Singh Jadav, Mohammed H. Geesi, Mohammed Afroz Bakht, Mohd. Zaheen Hassan, Abdulmalik Bin Saleh Al-Tamimi, Yassine Riadi , Salahuddin, Afzal Hussain, Narayan Murthy Ganta, Habibullah Khalilullah.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Cancer caused nearly 8.8 million deaths in 2015. Limited efficacy, selectivity, drug resistance and toxicity are major complications associated with chemotherapy, potentiating the discovery of anticancer agents.

Methods: A new series of N-(7-hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide analogues (5a-j) was prepared from the precursor, 7-hydroxy-4-methyl-2H-chromen-2-one (3), as anticancer agent. The structural assignment of quinolone analogues (5a-j) was based on spectroscopic data analyses. The cytotoxicity was tested on breast cancer cell lines (MCF7 and MDA-MB- 231) by sulforhodamine B (SRB) assay and three dose-related parameters GI50, TGI, and LC50 were calculated.

Results: 2-(2-chlorophenoxy)-N-(7-hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide (5a) showed the most potent cytotoxicity against the MCF7 and MDA-MB-231 cancer cell lines with GI50 of 18.7 and 48.1 µM respectively. The glide scores of the compounds, 5a-d were found to be related to the cytotoxicity profile and the emodel scores for ligands, 5a-j were found to be related to significant cytotoxicity.

Conclusion: Compound 5a exhibited the most potent cytotoxicity and this report may provide some predictions to design more potent novel quinolines as cytotoxic agents.

Keywords: Anticancer agents, breast cancer cell lines, EGFR tyrosine kinase, SRB assay, quinolones.

[1]
World Health Organization Cancer, Key facts. Available from:. http://www.who.int/mediacentre/factsheets/fs297/en/
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. 2017 Cancer Statistics. CA Cancer J. Clin., 2017, 67, 7-30.
[3]
Cancer fact sheet February 2017: Available from http://www.who.int/news-room/fact-sheets
[4]
Nandakumar, A. National cancer registry programme. indian council for medical research, consolidated report of the population based cancer registries 1990-96.New Delhi; Indian Council of Medical Research, 2009.
[5]
Bray, F.; Ren, J.S.; Masuyer, E.; Ferlay, J. Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int. J. Cancer, 2013, 132, 1133-1145.
[6]
DeSantis, C.E.; Ma, J.; Sauer, A.G.; Newman, L.A.; Jemal, A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J. Clin., 2017, 67, 439-448.
[7]
Heiniger, B.; Gakhar, G.; Prasain, K.; Hua, D.H.; Nguyen, T.A. Second-generation substituted quinolines as anticancer drugs for breast cancer. Anticancer Res., 2010, 30, 3927-3932.
[8]
Abdellatif, K.R.A.; Abdelall, E.K.A.; Abdelgawad, M.A.; Amin, D.M.E.; Omar, H.A. Design, synthesis and biological evaluation of new 4-(4-substitutedanilino) quinoline derivatives as anticancer agents. Med. Chem. Res., 2017, 26, 929-939.
[9]
Pawar, V.G.; Sos, M.L.; Rode, H.B.; Rabiller, M.; Heynck, S.; vanOttaerlo, W.A.L.; Thomas, R.K.; Rauh, D. Synthesis and biological evaluation of 4-Anilinoquinolines as potent inhibitors of epidermal growth factor receptor. J. Med. Chem., 2010, 53, 2892-2901.
[10]
Li, S.; Guo, C.; Sun, X.; Li, Y.; Zhao, H.; Zhan, Z.; Lan, M.; Tang, Y. Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors and EPR bio-probe agents. Eur. J. Med. Chem., 2012, 49, 271-278.
[11]
Aly, R.M.; Serya, R.A.T.; El-Motawally, A.M.; Esmat, A.; Abbas, S.; El-Ella, D.A.A. Novel quinoline-3-carboxamides (Part 2): Design, optimization and synthesis of quinoline based scaffold as EGFR inhibitors with potent anticancer activity. Bioorg. Chem., 2017, 75, 368-392.
[12]
Thigulla, Y.; Akula, M.; Trivedi, P.; Ghosh, B.; Jha, M.; Bhattacharya, A. Synthesis and anti-cancer activity of 1, 4-disubstituted imidazo[4,5-c]quinolines. Org. Biomol. Chem., 2016, 14, 876-883.
[13]
Musiol, R. An overview of quinoline as a privileged scaffold in cancer drug discovery. Expert Opin. Drug Discov., 2017, 12(6), 583-597.
[14]
Ghorab, M.M.; Ragab, F.A.; Heiba, H.I.; Ghorab, W.M. Design and synthesis of some novel quinoline derivatives as anticancer and radiosensitizing agents targeting VEGFR tyrosine kinase. J. Het. Chem, 2011, 48, 1269-1279.
[15]
Afzal, O.; Kumar, S.; Haider, M.R.; Ali, M.R.; Kumar, R.; Jaggi, M.; Bawa, S. A review on anticancer potential of bioactive heterocycles quinoline. Eur. J. Med. Chem., 2015, 97, 871-910.
[16]
Ahsan, M.J.; Shastri, S.; Yadav, R.; Jadav, S.S.; Bakht, M.A.; Hasan, M.Z.; Yasmin, S. Synthesis and anticancer activity of some quinoline and oxadiazole analogues.Org. Chem. Int., 2016, Article ID 9589517, 10 pages;
[17]
Topliss, J.G. Utilization of operational scheme for analog synthesis in drug design. J. Med. Chem., 1972, 15, 1006-1011.
[18]
Kar, A. 2004 Advanced Practical Medicinal Chemistry; New Age International Publishers: New Delhi, 2004, pp. 131-132.
[19]
Ahsan, M.J.; Ansari, M.Y.; Kumar, P.; Soni, M.; Yasmin, S.; Jadav, S.S.; Sahoo, G.C. In vitro studies of the antileishmanial activity of the newer 2-(substitutedphenoxy)-N-[(aryl)methylidene] acetohydrazide analogues. Beni-Seuf Univ. J. Basic Appl. Sci., 2016, 5, 119-125.
[20]
ShaharYar. M.; Siddiqui, A.A.; Ali, M.A. Synthesis and anti tuberculostatic activity of novel 1,3,4-oxadiazole derivatives. J. Chin. Chem. Soc. , 2007, 54, 5-8.
[21]
[a]. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 83, 1107-11012, [b]. Vichai V.; Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protocol., 2006, 1, 1112-1116.
[22]
Ransom, M. Epidermal growth factor receptor tyrosine kinase inhibitors. British J. Cancer, 2004, 90, 2250-2255
[23]
Pritien Data Bank, RCSB. Avaliable from . http://www.rcsb.org/
pdb/explore.do?structureId=2j5f
[24]
Laskowski, R.A.; Swindells, M.B. LigPlot: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model., 2011, 51, 2778-2786.
[25]
Lipinski, C.A.; Lombardo, L.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery. Rev., 2001, 46, 3-26.
[26]
Patrick, G.L. An Introduction to Medicinal Chemistry, 3rd ed; Oxford University Press Inc.: New York, 2005, pp. 271-298.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 2
Year: 2019
Page: [182 - 193]
Pages: 12
DOI: 10.2174/1570180815666180501160047
Price: $58

Article Metrics

PDF: 20
HTML: 3
PRC: 1