Exploring Quinolone Scaffold: Unravelling the Chemistry of Anticancer
Drug Design

Vishal       Sharma; Rina       Das; Dinesh    Kumar    Mehta; Diksha       Sharma; Ram    Kumar    Sahu
doi:10.2174/1389557521666210112142136
Abstract

Abstract: Globally, cancer is considered as the major leading cause in burdening the patient’s health care system globally. The growing threat of drug-resistant cancers renders an urgent need to develop more successful candidates for the anti-cancer therapy. In view of the outstanding pharmacological activities, Quinolone and its derivatives have attracted more attention towards drug designing and biological evaluation in the search for new drug molecules. The inspired researchers attempted efforts in order to discover the quinolone based analogs due to their wide range of biological activities. Due to immense pharmacological importance, distinct synthetic methods have been executed to attain new drug entities from quinolones and all the reported molecules have shown constructive anticancer activities. Some of the synthetic protocols like one pot synthesis, post-Ugi-transformation, catalysed based synthesis, enzyme-based synthesis and nano-catalyst based synthetic procedures are also discussed as recent advancements in the production of quinolone derivatives. In this review, recent synthetic approaches in the medicinal chemistry of quinolones and potent quinolone derivatives on the basis of structural activity relationship are outlined. Moreover, their major methods and modifications are discussed.
Keywords: Cancer, HIV, heterocyclic, medicinal chemistry, quinolone, synthesis.
« Previous
Graphical Abstract

[1] 
Rashid, H.U.; Xu, Y.; Muhammad, Y.; Wang, L.; Jiang, J. Research advances on anticancer activities of matrine and its derivatives: An updated overview. Eur. J. Med. Chem.,  2019, 161, 205-238.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.037] [PMID: 30359819] 
[2] 
Elghazawy, N.H.; Hefnawy, A.; Sedky, N.K.; El-Sherbiny, I.M.; Arafa, R.K. Preparation and nanoformulation of new quinolone scaffold-based anticancer agents: Enhancing solubility for better cellular delivery. Eur. J. Pharm. Sci.,  2017, 105, 203-211.
[http://dx.doi.org/10.1016/j.ejps.2017.05.036] [PMID: 28526600] 
[3] 
Sharma, P.C.; Kaur, G.; Pahwa, R.; Sharma, A.; Rajak, H. Quinazolinone analogs as potential therapeutic agents. Curr. Med. Chem.,  2011, 18(31), 4786-4812.
[http://dx.doi.org/10.2174/092986711797535326] [PMID: 21919847] 
[4] 
Counihan, J.L.; Grossman, E.A.; Nomura, D.K. Cancer metabolism: current understanding and therapies. Chem. Rev.,  2018, 118(14), 6893-6923.
[http://dx.doi.org/10.1021/acs.chemrev.7b00775] [PMID: 29939018] 
[5] 
Hassanpour, S.H.; Dehghani, M. Review of cancer from perspective of molecular. J. Cancer Res. Pract,  2017, 4(4), 127-129.
[http://dx.doi.org/10.1016/j.jcrpr.2017.07.001] 
[6] 
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA cancer J. Clin.,  2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855] 
[7] 
Heidari-Asil, S.A.; Zinatloo-Ajabshir, S.; Amiri, O.; Salavati-Niasari, M. Amino acid assisted-synthesis and characterization of magnetically retrievable ZnCo2O4–Co3O4 nanostructures as high activity visible-light-driven photocatalyst. Int. J. Hydrogen Energy, 2020.
[http://dx.doi.org/10.1016/j.ijhydene.2020.06.122] 
[8] 
Zinatloo-Ajabshir, S.; Salehi, Z.; Amiri, O.; Salavati-Niasari, M. Green synthesis, characterization and investigation of the electrochemical hydrogen storage properties of Dy2Ce2O7 nanostructures with fig extract. Int. J. Hydrogen Energy, 2019.
[http://dx.doi.org/10.1016/j.ijhydene.2019.05.137] 
[9] 
Banerjee, S.; Payra, S.; Saha, A.; Sereda, G. ZnO nanoparticles: a green efficient catalyst for the room temperature synthesis of biologically active 2-aryl-1,3-benzothiazole and 1,3-benzoxazole derivatives. Tetrahedron Lett.,  2014, 55(40), 5515-5520.
[http://dx.doi.org/10.1016/j.tetlet.2014.07.123] 
[10] 
Zinatloo-Ajabshir, S.; Salehi, Z.; Amiri, O.; Salavati-Niasari, M. Simple fabrication of Pr2Ce2O7 nanostructures via a new and eco-friendly route; A potential electrochemical hydrogen storage material. J. Alloys Compd.,  2019, 791, 792-799.
[http://dx.doi.org/10.1016/j.jallcom.2019.04.005] 
[11] 
Ozdemir, S.B. Synthesis of novel fluoroquinolone-triazole hybrid compounds as antimicrobial agents. J. Turkish Chem. Soc. Sect. A: Chem,  2016, 3(3), 515-534.
[12] 
Bisacchi, G.S. Origins of the quinolone class of antibacterials: an expanded “discoverystory”. J. Med. Chem.,  2015, 58(12), 4874-4882.
[http://dx.doi.org/10.1021/jm501881c] [PMID: 25738967] 
[13] 
Heeb, S.; Fletcher, M.P.; Chhabra, S.R.; Diggle, S.P.; Williams, P.; Cámara, M. Quinolones: from antibiotics to autoinducers. FEMS Microbiol. Rev.,  2011, 35(2), 247-274.
[http://dx.doi.org/10.1111/j.1574-6976.2010.00247.x] [PMID: 20738404] 
[14] 
Hu, Y.Q.; Zhang, S.; Xu, Z.; Lv, Z.S.; Liu, M.L.; Feng, L.S. 4-Quinolone hybrids and their antibacterial activities. Eur. J. Med. Chem.,  2017, 141, 335-345.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.050] [PMID: 29031077] 
[15] 
Zhang, G.F.; Liu, X.; Zhang, S.; Pan, B.; Liu, M.L. Ciprofloxacin derivatives and their antibacterial activities. Eur. J. Med. Chem.,  2018, 146, 599-612.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.078] [PMID: 29407984] 
[16] 
Fan, Y.L.; Wu, J.B.; Cheng, X.W.; Zhang, F.Z.; Feng, L.S. Fluoroquinolone derivatives and their anti-tubercular activities. Eur. J. Med. Chem.,  2018, 146, 554-563.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.080] [PMID: 29407980] 
[17] 
Xu, Z.; Song, X.F.; Hu, Y.Q.; Qiang, M.; Lv, Z.S. Azide-alkyne cycloaddition towards 1H-1,2,3-triazole-tethered gatifloxacin and isatin conjugates: Design, synthesis and in vitro anti-mycobacterial evaluation. Eur. J. Med. Chem.,  2017, 138, 66-71.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.057] [PMID: 28646656] 
[18] 
Fan, Y.L.; Cheng, X.W.; Wu, J.B.; Liu, M.; Zhang, F.Z.; Xu, Z.; Feng, L.S. Antiplasmodial and antimalarial activities of quinolone derivatives: An overview. Eur. J. Med. Chem.,  2018, 146, 1-14.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.039] [PMID: 29360043] 
[19] 
Winter, R.; Kelly, J.X.; Smilkstein, M.J.; Hinrichs, D.; Koop, D.R.; Riscoe, M.K. Optimization of endochin-like quinolones for antimalarial activity. Exp. Parasitol.,  2011, 127(2), 545-551.
[http://dx.doi.org/10.1016/j.exppara.2010.10.016] [PMID: 21040724] 
[20] 
Sekgota, K.C.; Majumder, S.; Isaacs, M.; Mnkandhla, D.; Hoppe, H.C.; Khanye, S.D.; Kriel, F.H.; Coates, J.; Kaye, P.T. Application of the Morita-Baylis-Hillman reaction in the synthesis of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1 integrase inhibitors. Bioorg. Chem.,  2017, 75, 310-316.
[http://dx.doi.org/10.1016/j.bioorg.2017.09.015] [PMID: 29080495] 
[21] 
Tabarrini, O.; Massari, S.; Daelemans, D.; Stevens, M.; Manfroni, G.; Sabatini, S.; Balzarini, J.; Cecchetti, V.; Pannecouque, C.; Fravolini, A. Structure-activity relationship study on anti-HIV 6-desfluoroquinolones. J. Med. Chem.,  2008, 51(17), 5454-5458.
[http://dx.doi.org/10.1021/jm701585h] [PMID: 18710207] 
[22] 
Gao, F.; Zhang, X.; Wang, T.; Xiao, J. Quinolone hybrids and their anti-cancer activities: An overview. Eur. J. Med. Chem.,  2019, 165, 59-79.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.017] [PMID: 30660827] 
[23] 
Beteck, R.M.; Smit, F.J.; Haynes, R.K.; N’Da, D.D. Recent progress in the development of anti-malarial quinolones. Malar. J.,  2014, 13, 339.
[http://dx.doi.org/10.1186/1475-2875-13-339] [PMID: 25176157] 
[24] 
Hepnarova, V.; Korabecny, J.; Matouskova, L.; Jost, P.; Muckova, L.; Hrabinova, M.; Vykoukalova, N.; Kerhartova, M.; Kucera, T.; Dolezal, R.; Nepovimova, E.; Spilovska, K.; Mezeiova, E.; Pham, N.L.; Jun, D.; Staud, F.; Kaping, D.; Kuca, K.; Soukup, O. The concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (BQCA) as multifunctional agents for Alzheimer’s disease. Eur. J. Med. Chem.,  2018, 150, 292-306.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.083] [PMID: 29533874] 
[25] 
Mermer, A.; Demirbaş, N.; Şirin, Y.; Uslu, H.; Özdemir, Z.; Demirbaş, A. Conventional and microwave prompted synthesis, antioxidant, anticholinesterase activity screening and molecular docking studies of new quinolone-triazole hybrids. Bioorg. Chem.,  2018, 78, 236-248.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.017] [PMID: 29614435] 
[26] 
Tretter, E.M.; Berger, J.M. Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates escherichia coli gyrase activity. J. Biol. Chem.,  2012, 287(22), 18636-18644.
[http://dx.doi.org/10.1074/jbc.M112.345678] [PMID: 22457353] 
[27] 
Aldred, K.J.; Kerns, R.J.; Osheroff, N. Mechanism of quinolone action and resistance. Biochemistry,  2014, 53(10), 1565-1574.
[http://dx.doi.org/10.1021/bi5000564] [PMID: 24576155] 
[28] 
Sidhu, G.S.; Go, A.; Attar, B.M.; Mutneja, H.R.; Arora, S.; Patel, S.A. Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: A systematic review. BMJ Open Gastro,  2017, 4(1)
[29] 
Makhanya, T.R.; Gengan, R.M.; Pandian, P.; Chuturgoon, A.A.; Tiloke, C.; Atar, A. Phosphotungstic acid catalyzed one pot synthesis of 4,8,8-trimethyl-5- phenyl-5,5a,8,9-tetrahydrobenzo[b][1,8]naphthyridin-6(7H)-one derivatives and their biological evaluation against A549 lung cancer cells. J. Heterocycl. Chem.,  2018, 55(5), 1193-1204.
[http://dx.doi.org/10.1002/jhet.3153] 
[30] 
Musiol, R. An overview of quinoline as a privileged scaffold in cancer drug discovery. Expert Opin. Drug Discov.,  2017, 12(6), 583-597.
[http://dx.doi.org/10.1080/17460441.2017.1319357] [PMID: 28399679] 
[31] 
Ezerlarab, H.A.A.; Abbas, S.H.; Hassan, H.A.; Abuo-Rahma, G.E.A. Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm,  2018, 351(9), 1-13.
[32] 
Chu, X.M.; Wang, C.; Liu, W.; Liang, L-L.; Gong, K-K.; Zhao, C-Y.; Sun, K.L. Quinoline and quinolone dimers and their biological activities: An overview. Eur. J. Med. Chem.,  2019, 161, 101-117.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.035] [PMID: 30343191] 
[33] 
Raghavan, S.; Manogaran, P.; Gadepalli Narasimha, K.K.; Kalpattu Kuppusami, B.; Mariyappan, P.; Gopalakrishnan, A.; Venkatraman, G. Synthesis and anticancer activity of novel curcumin-quinolone hybrids. Bioorg. Med. Chem. Lett.,  2015, 25(17), 3601-3605.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.068] [PMID: 26174555] 
[34] 
Smart, D.J.; Halicka, H.D.; Traganos, F.; Darzynkiewicz, Z.; Williams, G.M. Ciprofloxacin-induced G2 arrest and apoptosis in TK6 lymphoblastoid cells is not dependent on DNA double-strand break formation. Cancer Biol. Ther.,  2008, 7(1), 113-119.
[http://dx.doi.org/10.4161/cbt.7.1.5136] [PMID: 18059176] 
[35] 
Yadav, V.; Talwar, P. Repositioning of fluoroquinolones from antibiotic to anti-cancer agents: An underestimated truth. Biomed. Pharmacother.,  2019, 111, 934-946.
[http://dx.doi.org/10.1016/j.biopha.2018.12.119] [PMID: 30841473] 
[36] 
Beberok, A.; Rzepka, Z.; Respondek, M.; Rok, J.; Sierotowicz, D.; Wrześniok, D. GSH depletion, mitochondrial membrane breakdown, caspase-3/7 activation and DNA fragmentation in U87MG glioblastoma cells: New insight into the mechanism of cytotoxicity induced by fluoroquinolones. Eur. J. Pharmacol.,  2018, 835, 94-107.
[http://dx.doi.org/10.1016/j.ejphar.2018.08.002] [PMID: 30086267] 
[37] 
Gürbay, A.; Osman, M.; Favier, A.; Hincal, F. Ciprofloxacin-induced cytotoxicity and apoptosis in HeLa cells. Toxicol. Mech. Methods,  2005, 15(5), 339-342.
[http://dx.doi.org/10.1080/153765291009877] [PMID: 20021053] 
[38] 
Shi, Z.Y.; Li, Y.Q.; Kang, Y.H.; Hu, G.Q.; Huang-fu, C.S.; Deng, J.B.; Liu, B. Piperonal ciprofloxacin hydrazone induces growth arrest and apoptosis of human hepatocarcinoma SMMC-7721 cells. Acta Pharmacol. Sin.,  2012, 33(2), 271-278.
[http://dx.doi.org/10.1038/aps.2011.158] [PMID: 22301863] 
[39] 
Mohammadhosseini, N.; Alipanahi, Z.; Alipour, E.; Emami, S.; Faramarzi, M.A.; Samadi, N.; Khoshnevis, N.; Shafiee, A.; Foroumadi, A. Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety. Daru,  2012, 20(1), 16.
[http://dx.doi.org/10.1186/2008-2231-20-16] [PMID: 23351676] 
[40] 
Rajulu, G.G.; Bhojya Naik, H.S.; Viswanadhan, A.; Thiruvengadam, J.; Rajesh, K.; Ganesh, S.; Jagadheshan, H.; Kesavan, P.K. New hydroxamic acid derivatives of fluoroquinolones: Synthesis and evaluation of antibacterial and anticancer properties. Chem. Pharm. Bull. (Tokyo),  2014, 62(2), 168-175.
[http://dx.doi.org/10.1248/cpb.c13-00797] [PMID: 24270473] 
[41] 
Abdel-Aal, M.A.A.; Abdel-Aziz, S.A.; Shaykoon, M.S.A.; Abuo-Rahma, G.E.A. Towards anticancer fluoroquinolones: A review article. Arch. Pharm. (Weinheim),  2019, 352(7)
[http://dx.doi.org/10.1002/ardp.201800376] [PMID: 31215674] 
[42] 
Senerovic, L.; Opsenica, D.; Moric, I.; Aleksic, I.; Spasic, M.; Vasiljevic, B. Quinolines and quinolones as antibacterial, antifungal, anti-virulence, antiviral and anti-parasitic agents.advances in microbiology, infectious Diseases and Public Health. advances in experimental medicine and biology; Donelli, G., Ed.; Springer: Cham, 2019, Vol. 1282, pp. 37-69.
[http://dx.doi.org/10.1007/5584_2019_428] 
[43] 
Xu, X.M.; Luo, Z.G.; He, K.; Zhang, M.Y. Synthesis and Biological Evaluation of Quinolone Acid Derivatives Having Polyhydroxylated Aromatics as HIV-1 Integrase Inhibitions. Adv. Mat. Res.,  2013, 634-638, 1116-1119.
[http://dx.doi.org/10.4028/www.scientific.net/AMR.634-638.1116] 
[44] 
Hu, L.; Yan, S.; Luo, Z.; Han, X.; Wang, Y.; Wang, Z.; Zeng, C. Design, practical synthesis, and biological evaluation of novel 6-(pyrazolylmethyl)-4-quinoline-3-carboxylic acid derivatives as HIV-1 integrase inhibitors. Molecules,  2012, 17(9), 10652-10666.
[http://dx.doi.org/10.3390/molecules170910652] [PMID: 22955454] 
[45] 
Foroumadi, A.; Emami, S.; Rajabalian, S.; Badinloo, M.; Mohammadhosseini, N.; Shafiee, A. N-Substituted piperazinyl quinolones as potential cytotoxic agents: structure-activity relationships study. Biomed. Pharmacother.,  2009, 63(3), 216-220.
[http://dx.doi.org/10.1016/j.biopha.2008.01.016] [PMID: 18328669] 
[46] 
Feng, L.; Lv, K.; Liu, M.; Wang, S.; Zhao, J.; You, X.; Li, S.; Cao, J.; Guo, H. Synthesis and in vitro antibacterial activity of gemifloxacin derivatives containing a substituted benzyloxime moiety. Eur. J. Med. Chem.,  2012, 55, 125-136.
[http://dx.doi.org/10.1016/j.ejmech.2012.07.010] [PMID: 22841282] 
[47] 
Zhang, Y.B.; Feng, L.S.; You, X.F.; Guo, Q.; Guo, H.Y.; Liu, M.L. Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)-fluoroquinolone derivatives. Arch. Pharm. (Weinheim),  2010, 343(3), 143-151.
[http://dx.doi.org/10.1002/ardp.200900191] [PMID: 20186866] 
[48] 
Asif, M. A review on anticancer and antimicrobial activity of tetrafluoroquinolone compounds. Annals Med. Chem. Res,  2014, 1(1), 1-10.
[49] 
Jiang, D. 4-Quinolone derivatives and their activities against gram-negative pathogens. J. Heterocycl. Chem.,  2018, 55, 2003.
[http://dx.doi.org/10.1002/jhet.3244] 
[50] 
Adhikari, N.; Halder, A.K.; Mondal, C.; Jha, T. Structural findings of quinolone carboxylic acids in cytotoxic, antiviral, and anti-HIV-1 integrase activity through validated comparative molecular modeling studies. Med. Chem. Res.,  2014, 23, 3096-3127.
[http://dx.doi.org/10.1007/s00044-013-0897-5] 
[51] 
Gupta, M.; Madan, A.K. Diverse models for the prediction of HIV integrase inhibitory activity of substituted quinolone carboxylic acids. Arch. Pharm. (Weinheim),  2012, 345(12), 989-1000.
[http://dx.doi.org/10.1002/ardp.201100316] [PMID: 22945879] 
[52] 
Wang, R.; Xu, K.; Shi, W. Quinolone derivatives: Potential anti‐HIV agent—development and application. Archiv. Der. Pharmazie,  2019, 1-17.
[http://dx.doi.org/10.1002/ardp.201900045] 
[53] 
Gao, C.; Chang, L.; Xu, Z.; Yan, X-F.; Ding, C.; Zhao, F.; Wu, X.; Feng, L.S. Recent advances of tetrazole derivatives as potential anti-tubercular and anti-malarial agents. Eur. J. Med. Chem.,  2019, 163, 404-412.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.001] [PMID: 30530192] 
[54] 
Royle, C.M.; Tsai, M-H.; Tabarrini, O.; Massari, S.; Graham, D.R.; Aquino, V.N.; Boasso, A. Modulation of HIV-1-induced activation of plasmacytoid dendritic cells by 6-desfluoroquinolones. AIDS Res. Hum. Retroviruses,  2014, 30(4), 345-354.
[http://dx.doi.org/10.1089/aid.2013.0154] [PMID: 24229417] 
[55] 
Ezelarab, H.A.A.; Abbas, S.H.; Hassan, H.A.; Abuo-Rahma, G.E-D.A. Recent updates of fluoroquinolones as antibacterial agents. Archiv. Der. Pharmazie, 2018.
[http://dx.doi.org/10.1002/ardp.201800141] 
[56] 
Parizadeh, N.; Alipour, E.; Soleymani, S.; Zabihollahi, R.; Aghasadeghi, M.R.; Hajimahdi, Z.; Zarghi, A. Synthesis of novel 3-(5-(Alkyl/arylthio)-1,3,4-Oxadiazol-2-yl)-8-Phenylquinolin-4(1H)-one derivatives as anti-HIV agents. Phosphorus Sulfur Silicon Relat. Elem.,  2017, 193(4), 225-231.
[http://dx.doi.org/10.1080/10426507.2017.1394302] 
[57] 
Gao, F.; Wang, P.; Yang, H.; Miao, Q.; Ma, L.; Lu, G. Recent developments of quinolone-based derivatives and their activities against Escherichia coli. Eur. J. Med. Chem.,  2018, 157, 1223-1248.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.095] [PMID: 30193220] 
[58] 
Emami, S.; Foroumadi, A.; Faramarzi, M.A.; Samadi, N. Synthesis and antibacterial activity of quinolone-based compounds containing a coumarin moiety. Arch. Pharm. (Weinheim),  2008, 341(1), 42-48.
[http://dx.doi.org/10.1002/ardp.200700090] [PMID: 18072241] 
[59] 
Biswas, A.; Giri, D.; Das, D.; De, A.; Patra, S.K.; Samanta, R. A mild rhodium catalyzed direct synthesis of quinolones from pyridones: application in the detection of nitroaromatics. J. Org. Chem.,  2017, 82(20), 10989-10996.
[http://dx.doi.org/10.1021/acs.joc.7b01932] [PMID: 28901761] 
[60] 
Cross, R.M.; Namelikonda, N.K.; Mutka, T.S.; Luong, L.; Kyle, D.E.; Manetsch, R. Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones. J. Med. Chem.,  2011, 54(24), 8321-8327.
[http://dx.doi.org/10.1021/jm200718m] [PMID: 22111907] 
[61] 
Suthar, S.K.; Jaiswal, V.; Lohan, S.; Bansal, S.; Chaudhary, A.; Tiwari, A.; Alex, A.T.; Joesph, A. Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: design, synthesis and biological screening. Eur. J. Med. Chem.,  2013, 63, 589-602.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.011] [PMID: 23548704] 
[62] 
Shou, K.J.; Li, J.; Jin, Y.; Lv, Y.W. Design, synthesis, biological evaluation, and molecular docking studies of quinolone derivatives as potential antitumor topoisomerase I inhibitors. Chem. Pharm. Bull. (Tokyo),  2013, 61(6), 631-636.
[http://dx.doi.org/10.1248/cpb.c13-00040] [PMID: 23558565] 
[63] 
Duarte, P.D.; Paixao, M.W.; Correa, A.G. Microwave assisted synthesis of 4-quinolones and N, N′-diarylureas. Green Process. Synth.,  2013, 2(1), 19-24.
[http://dx.doi.org/10.1515/gps-2012-0083] 
[64] 
Voigt, B.; Albrecht, D.; Dalhoff, A. Mode of action of mcb3681 in staphylococcus aureus– a proteomic study. Arch. Clin. Microbiol,  2016, 7, 6.
[http://dx.doi.org/10.4172/1989-8436.100061] 
[65] 
Freeman, J.; Pilling, S.; Vernon, J.; Wilcox, M.H. In vitro activities of mcb3681 and eight comparators against clostridium difficile isolates with known ribotypes and diverse geographical spread. Antimicrob. Agents Chemother.,  2017, 61(3), 02077-16.
[http://dx.doi.org/10.1128/AAC.02077-16] [PMID: 27993853] 
[66] 
Nakai, K.; Kurahashi, T.; Matsubara, S. Synthesis of quinolones by nickel-catalyzed cycloaddition via elimination of nitrile. Org. Lett.,  2013, 15(4), 856-859.
[http://dx.doi.org/10.1021/ol303546p] [PMID: 23351012] 
[67] 
Du, X.; Huang, J.; Nechaev, A.A.; Yao, R.; Gong, J.; Van der Eycken, E.V.; Pereshivko, O.P.; Peshkov, V.A. Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones. Beilstein J. Org. Chem.,  2018, 14, 2572-2579.
[http://dx.doi.org/10.3762/bjoc.14.234] [PMID: 30410618] 
[68] 
Singh, K.; Malviya, B.K.; Verma, V.P.; Badsara, S.S.; Bhardwaj, V.K.; Sharma, S. Cationic Pd(II) catalyzed regioselective intramolecular hydroarylation for the efficient synthesis of 4-aryl-2-quinolones. Tetrahedron,  2019, 75(17), 2506-2520.
[http://dx.doi.org/10.1016/j.tet.2019.03.026] 
[69] 
Resmi, M.S.; Verma, P.; Gokhale, R.S.; Soniya, E.V. Identification and characterization of a type III polyketide synthase involved in quinolone alkaloid biosynthesis from Aegle marmelos Correa. J. Biol. Chem.,  2013, 288(10), 7271-7281.
[http://dx.doi.org/10.1074/jbc.M112.429886] [PMID: 23329842] 
[70] 
Gao, W.C.; Liu, T.; Cheng, Y-F.; Chang, H-H.; Li, X.; Zhou, R.; Wei, W.L.; Qiao, Y. AlCl3-catalyzed intramolecular cyclization of n-arylpropynamides with n-sulfanylsuccinimides: divergent synthesis of 3-sulfenyl quinolin-2-ones and azaspiro [4, 5] trienones. J. Org. Chem.,  2017, 82(24), 13459-13467.
[http://dx.doi.org/10.1021/acs.joc.7b02498] [PMID: 29129066] 
[71] 
Jarriage, L.; Zaied, S.; Merad, J.; Blanchard, F.; Masson, G. Easy access to quinolin- 2(1H)-ones via a one pot tandem Oxa-Michael-Aldol sequence. Synlett,  2017, 28(14), 1724-1728.
[http://dx.doi.org/10.1055/s-0036-1588470] 
[72] 
Shimokawa, Y.; Morita, H.; Abe, I. Benzalacetone synthase. Front. Plant Sci.,  2012, 3, 57-62.
[http://dx.doi.org/10.3389/fpls.2012.00057] [PMID: 22645592] 
[73] 
Wang, J.; Wang, X-H.; Liu, X.; Li, J.; Shi, X-P.; Song, Y-L.; Zeng, K-W.; Zhang, L.; Tu, P-F.; Shi, S-P. Synthesis of unnatural 2- substituted quinolones and 1,3-diketones by a member of type III polyketide synthases from huperzia serrata. Org. Lett.,  2016, 18(15), 3550-3553.
[http://dx.doi.org/10.1021/acs.orglett.6b01501] [PMID: 27399835] 
[74] 
Zhang, P.; Zheng, H.; Gu, H.; Zhang, W.; Wang, N. Chinese patent ZL 201010513580.6, 2014.
[75] 
Shen, C.; Shen, H.Y.; Yang, M.; Xia, C.C.; Zhang, P.F. A novel D-glucosaminederived pyridyl-triazole@ palladium catalyst for solvent-free Mizoroki–Heck reactions and its application in the synthesis of axitinib. Green Chem.,  2015, 17, 225-230.
[http://dx.doi.org/10.1039/C4GC01606H] 
[76] 
Shen, H.; Shen, C.; Chen, C.; Wang, A.; Zhang, P. Novel glycosyl pyridyltriazole@ palladium nanoparticles: efficient and recoverable catalysts for C-C cross couplings. Catal. Sci. Technol.,  2015, 5, 2065-2071.
[http://dx.doi.org/10.1039/C5CY00013K] 
[77] 
Rueping, M.; Moreth, S.A.; Bolte, M.Z. Asymmetric brønsted acid-catalyzed intramolecular aza-Michael reaction enantioselective synthesis of dihydroquinolinones; Naturforsch, 2015, pp. 1021-1029.
[78] 
Wang, X.; Jiang, X.; Sun, S.; Liu, Y. Synthesis and biological evaluation of novel quinolone derivatives dual targeting histone deacetylase and tubulin polymerization as antiproliferative agents. RSC Advances,  2018, 8(30), 16494-16502.
[http://dx.doi.org/10.1039/C8RA02578A] 
[79] 
Khalil, O.M.; Gedawy, E.M.; El-Malah, A.A.; Adly, M.E. Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg. Chem.,  2019, 83, 262-276.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.058] [PMID: 30391699] 
[80] 
Towle, T.R.; Kulkarni, C.A.; Oppegard, L.M.; Williams, B.P.; Picha, T.A.; Hiasa, H.; Kerns, R.J. Design, synthesis, and evaluation of novel N-1 fluoroquinolone derivatives: Probing for binding contact with the active site tyrosine of gyrase. Bioorg. Med. Chem. Lett.,  2018, 28(10), 1903-1910.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.085] [PMID: 29661533] 
[81] 
Das, R.; Mehta, D.K.; Sharma, V. Quinolones: Understanding the drug designing to combat drug resistance. Anal in Pharmacology and Pharmaceutics,  2017, 2(17), 1-3.
[82] 
Cui, S.F.; Peng, L.P.; Zhang, H.Z.; Rasheed, S.; Vijaya Kumar, K.; Zhou, C.H. Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin. Eur. J. Med. Chem.,  2014, 86, 318-334.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.063] [PMID: 25173851] 
[83] 
Li, J.; Zheng, T.C.; Jin, Y.; Xu, J.G.; Yu, J.G.; Lv, Y.W. Synthesis, molecular docking and biological evaluation of quinolone derivatives as novel anticancer agents. Chem. Pharm. Bull. (Tokyo),  2018, 66(1), 55-60.
[http://dx.doi.org/10.1248/cpb.c17-00035] [PMID: 29118308] 
[84] 
Cheng, Y.Y.; Liu, C.Y.; Tsai, M.T.; Lin, H.Y.; Yang, J.S.; Wu, T.S.; Kuo, S.C.; Huang, L.J.; Lee, K.H. Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead. Bioorg. Med. Chem. Lett.,  2013, 23(18), 5223-5227.
[http://dx.doi.org/10.1016/j.bmcl.2013.06.083] [PMID: 23916255] 
[85] 
Mohamed, H.A.E.; Al-Shareef, H.F. Design, synthesis, anti-proliferative evaluation and cell cycle analysis of hybrid 2-quinolones. anticancer. Agents Med. Chem.,  2019, 19(9), 1132-1140.
[http://dx.doi.org/10.2174/1871520619666190319142934] [PMID: 30892164] 
[86] 
Rajput, S.; Gardner, C.R.; Failes, T.W.; Arndt, G.M.; Black, D.S.; Kumar, N. Synthesis and anticancer evaluation of 3-substituted quinolin-4-ones and 2,3-dihydroquinolin-4-ones. Bioorg. Med. Chem.,  2014, 22(1), 105-115.
[http://dx.doi.org/10.1016/j.bmc.2013.11.047] [PMID: 24332654] 
[87] 
Jean, J.; Farrell, D.S.; Farrelly, A.M.; Toomey, S.; Barlow, J.W. Design, synthesis and evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one based chalcones as cytotoxic agents. Heliyon,  2018, 4(9)
[http://dx.doi.org/10.1016/j.heliyon.2018.e00767] [PMID: 30191185] 
[88] 
Kumari, P.; Narayana, C.; Dubey, S.; Gupta, A.; Sagar, R. Correction: Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents. Org. Biomol. Chem.,  2018, 16(12), 2185.
[http://dx.doi.org/10.1039/C8OB90031K] [PMID: 29504011] 
[89] 
Lamie, P.F.; Philoppes, J.N. Design and synthesis of three series of novel antitumor–azo derivatives. Med. Chem. Res.,  2017, 26, 1228-1240.
[http://dx.doi.org/10.1007/s00044-017-1839-4] 
[90] 
Hassanin, H.M.; Elmoneam, W.R.A.; Mostafa, M.A. Synthesis and antitumor activity evaluation of different 2,5-dialkyloxazolopyrano[3,2-c] quinolinone derivatives. Med. Chem. Res.,  2018, 28, 28-38.
[http://dx.doi.org/10.1007/s00044-018-2259-9] 
[91] 
Mohammed, H.H.H.; Abd El-Hafeez, A.A.; Abbas, S.H.; Abdelhafez, E.M.N.; Abuo-Rahma, G.E.A. New antiproliferative 7-(4-(N-substituted carbamoylmethyl)piperazin-1-yl) derivatives of ciprofloxacin induce cell cycle arrest at G2/M phase. Bioorg. Med. Chem.,  2016, 24(19), 4636-4646.
[http://dx.doi.org/10.1016/j.bmc.2016.07.070] [PMID: 27555286] 
[92] 
Zhang, Z.; Xiao, X.; Su, T.; Wu, J.; Ren, J.; Zhu, J.; Zhang, X.; Cao, R.; Du, R. Synthesis, structure-activity relationships and preliminary mechanism of action of novel water-soluble 4-quinolone-3-carboxamides as antiproliferative agents. Eur. J. Med. Chem.,  2017, 140, 239-251.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.017] [PMID: 28942112] 
[93] 
Kassab, A.E.; Gedawy, E.M. Novel ciprofloxacin hybrids using biology oriented drug synthesis (BIODS) approach: Anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity. Eur. J. Med. Chem.,  2018, 150, 403-418.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.026] [PMID: 29547830] 
[94] 
Fedorowicz, J.; Sączewski, J. Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules. MonatshefteFürChemie - Chemical Monthly,  2018, 149(7), 1199-1245.
[http://dx.doi.org/10.1007/s00706-018-2215-x] 
[95] 
Wang, J.; Tsao, A.; Liu, X. Class of quinolone heterocyclic aromatic molecules for cancer treatment., Patent US10202357B2, 2019.
[96] 
Soong, J. Combination therapy of tetracyclic quinolone analogs for treating cancer., Patent US20170143737A1, 2017.
[97] 
Kuo, S.C.; Teng, C.M.; Lee, K.H.; Huang, L.J.; Chou, L.C.; Chang, C.S.; Sun, C.M.; Wu, T.S.; Pan, S.L.; Way, T.D.; Lee, J.C.; Chung, J.G.; Yang, J.S.; Chen, C.T.; Huang, C.C.; Huang, S.M. Phenyl-4-quinolones as anticancer agents., Patent US9029394B2, 2015.
[98] 
Wu, T.S.; Pan, S.L.; Way, T.D.; Lee, J.C.; Chung, J.G.; Yang, J.S.; Chen, C.T.; Huang, C.C.; Chou, L.C.; Kuo, S.C.; Teng, C.M.; Lee, K.H.; Huang, L.J.; Huang, S.M.; Chang, C.S.; Sun, C.M. Selenophene-4-quinolones as anticancer agents., Patent EP2468747B1, 2014.
[99] 
Kuo, S.C.; Lee, K.H.; Huang, L.J.; Chou, L.C.; Wu, T.S.; Way, T.D.; Chung, J.G.; Yang, J.S.; Huang, C.H.; Tsai, M.T. Synthesis and anticancer activity of aryl and heteroaryl-quinoline derivatives., Patent US8524740B2, 2013.
[100] 
Kuo, S.C.; Teng, C.M.; Lee, K.H.; Huang, L. J.; Chou, L.C.; Chang, C.S.; Sun, C.M.; Wu, T.S.; Pan, S.L.; Way, T.D.; Lee, J. C.; Chung, J.G.; Yang, J.S.; Chen, C.T.; Huang, C.C.; Huang, S.M. Hydrophilic derivatives of 2-Aryl-4-quinolones as anticancer agents., Patent US8440692B2, 2013.
[101] 
Tang, J.C.O.; Chan, A.S.C.; Lam, K. H.; Chan, S. H. Quinoline derivatives as anticancer agents., Patent WO2012083866A1, 2012.
[102] 
Chang, C.S.; Chen, C. T.; Chou, L.C.; Chung, J.G. Novel hydrophilic derivatives of 2-aryl-4-quinolones as anticancer agents., Patent EP2096924A1, 2009.
[103] 
Khire, U.; Liu, X. G.; Nagarathnam, D.; Wood, J.; Wang, L.; Liu, D.; Zhao, J.; Guernon, L.; Zhang, L. Quinolone carboxylic acid derivatives for treatment of hyper proliferative conditions., Patent US20070213339A1, 2007.
[104] 
Dumas, J.; Khire, U.; Lasch, S.; Nagarathnam, D.; Scott, W.J. Methods of treating cancer with quinolone carboxylic acid derivatives., Patent US20060142295A1, 2006.
[105] 
Yang, B.V. Substituted quinoline-2-one derives as antiproliferative agents., Patent US6844357B2, 2005.
[106] 
Kuo, S.C.; Huang, L. J.; Lai, Y. Y.; Chen, C.J.; Hsu, M.H.; Fang, Y. L.; Lee, K.H.; Tang, C. M. Substituted 2-Phenyl-4-quinolone-3-carboxylic acid compounds and their use as antitumor agents., Patent US6897316B2, 2005.
[107] 
Whitten, J.P.; Pierre, F.; Regan, C.; Schwaebe, M.; Nagasawa, J.Y.; Chua, P. Quinolone analogs., Patent US7816406B2, 2010.
[108] 
Kuo, S.C.; Teng, C.M.; Lee, K.H.; Huang, L.J.; Chou, L.C.; Chang, C.S.; Sun, C.M.; Wu, T.S.; Pan, S.L.; Way, T.D.; Lee, J.C.; Chung, J.G.; Yang, J.S.; Chen, C.T.; Huang, C.C.; Huang, S.M. Hydrophilic derivatives of 2-selenophene-4-quinolones as anticancer agents., Patent US 9,023,866 B2, 2015.
[109] 
Pommier, Y.; Marchand, C.; Selvam, P.; Dexheimer, T.; Maddali, K. Fluoroquinolone derivatives or sulfonamide moiety-containing compounds as inhibitors of tyrosyl-dnaphosphodiesterase (TDP1). Patent US8716295B2, 2014.
[110] 
Chu, K.S.; Che-Ming, T.; Kuo-Hsiung, L.; Li-Jiau, H.; Li-Chen, C.; Chih-Shiang, C.; Chung-Ming, S.; Tian-Shung, W.; Shiow-Lin, P.; Tzong-Der, W.; Jang-Chang, L. Novel hydrophilic derivatives of 2-Aryl-4-quinolones as anticancer agents., Patent NZ577130, 2007.
[111] 
Nagasawa, J.Y.; Pierre, F.; Haddach, M.; Schwaebe, M.; Darjania, L.; Whitten, J.P. Quinolone analogs and methods related thereto., Patent US8853234B2, 2014.
[112] 
Yang, B.V. Heterocyclic substituted quinolone-2-one derivatives as anticancer agents., Patent US6710209B2, 2004.
[113] 
Joseph, B.; Darro, F.; Guillaumet, G.; Kiss, R.; Frydman, A. Pharmaceutical compositions comprising 4-quinolones for treating cancers., Patent US6645983B1, 2003.
[114] 
Lee, K.H.; Xia, Y.; Yang, Z.Y.; Kuo, S.C. Fluorinated quinolones as antimitotic and antitumor agents., Patent US6569870B1, 2003.
Rights & Permissions Print Cite
Article Metrics
24
3
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1389557521666210112142136	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607
Mini-Reviews in Medicinal Chemistry

Exploring Quinolone Scaffold: Unravelling the Chemistry of Anticancer Drug Design

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract
