Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Quinoline-3-carboxylate Derivatives: A New Hope as an Antiproliferative Agent

Author(s): Ravi K. Mittal and Priyank Purohit*

Volume 20 , Issue 16 , 2020

Page: [1981 - 1991] Pages: 11

DOI: 10.2174/1871520620666200619175906

Price: $65

Abstract

Background: The quinoline scaffold has been an attraction due to its pharmacological activities such as anti-HIV, anti-neoplastic, anti-asthmatic, anti-tuberculotic, anti-fungal, and anti-bacterial.

Objective: The designed quinoline-3-carboxylate derivatives were synthesized through a two-step reaction and evaluated for antiproliferative activity against MCF-7 and K562 cell lines.

Methods: Synthesized compounds were characterized by modern analytical techniques like NMR, 2DNMR, mass, and IR. Moreover, the purity of compounds was analyzed through the HPLC. In the progress of biological results, all synthesized compounds were evaluated for antiproliferative activity against MCF-7 and K562 cell lines.

Results: The synthesized compounds exhibited micromolar inhibition in all over the ranges, however, some of the compounds showed better activity than the standard anticancer drug such, as 4m and 4n with the IC50 value of 0.33μM against the MCF-7 cell line, and the compounds 4k and 4m showed potential activity against the K562 cell line with the IC50 value of 0.28μM. The anti-cancer activities of compounds were found to be through the up-regulation of intrinsic apoptosis pathways.

Conclusion: The biological data of all compounds in both cell lines were utilized for the structural activity relationship of the quinoline-3-carboxylate pharmacophore. The active lead was further validated through rigorous in silico studies for the drug-likeness (QED) and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties.

Here in the present research is utilized for the demonstration of an important pharmacophore, which could be utilized for further development to become a lead as an anticancer agent with minimal toxicity.

Keywords: Cancer, activity, drug discovery, in silico, cell line, antiproliferative agent.

Graphical Abstract
[1]
Varmus, H. The new era in cancer research. Science, 2006, 312(5777), 1162-1165.
[http://dx.doi.org/10.1126/science.1126758 ] [PMID: 16728627]
[2]
El-Sayed, M.A.A.; El-Husseiny, W.M.; Abdel-Aziz, N.I.; El-Azab, A.S.; Abuelizz, H.A.; Abdel-Aziz, A.A.M. Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: Molecular docking study. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 199-209.
[http://dx.doi.org/10.1080/14756366.2017.1407926 ] [PMID: 29251017]
[3]
Vázquez, M.T.; Romero, M.; Pujol, M.D. Synthesis of novel 2,3-dihydro-1,4-dioxino[2,3-g]quinoline derivatives as potential antitumor agents. Bioorg. Med. Chem., 2004, 12(5), 949-956.
[http://dx.doi.org/10.1016/j.bmc.2003.12.024 ] [PMID: 14980607]
[4]
Musiol, R.; Jampilek, J.; Buchta, V.; Silva, L.; Niedbala, H.; Podeszwa, B.; Palka, A.; Majerz-Maniecka, K.; Oleksyn, B.; Polanski, J. Antifungal properties of new series of quinoline derivatives. Bioorg. Med. Chem., 2006, 14(10), 3592-3598.
[http://dx.doi.org/10.1016/j.bmc.2006.01.016 ] [PMID: 16458522]
[5]
Andries, K.; Verhasselt, P.; Guillemont, J.; Göhlmann, H.W.H.; Neefs, J-M.; Winkler, H.; Van Gestel, J.; Timmerman, P.; Zhu, M.; Lee, E.; Williams, P.; de Chaffoy, D.; Huitric, E.; Hoffner, S.; Cambau, E.; Truffot-Pernot, C.; Lounis, N.; Jarlier, V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science, 2005, 307(5707), 223-227.
[http://dx.doi.org/10.1126/science.1106753 ] [PMID: 15591164]
[6]
Musiol, R.; Jampilek, J.; Kralova, K.; Richardson, D.R.; Kalinowski, D.; Podeszwa, B.; Finster, J.; Niedbala, H.; Palka, A.; Polanski, J. Investigating biological activity spectrum for novel quinoline analogues. Bioorg. Med. Chem., 2007, 15(3), 1280-1288.
[http://dx.doi.org/10.1016/j.bmc.2006.11.020 ] [PMID: 17142046]
[7]
Ramesh, E.; Manian, R.D.R.S.; Raghunathan, R.; Sainath, S.; Raghunathan, M. Synthesis and antibacterial property of quinolines with potent DNA gyrase activity. Bioorg. Med. Chem., 2009, 17(2), 660-666.
[http://dx.doi.org/10.1016/j.bmc.2008.11.058 ] [PMID: 19097914]
[8]
Mrozek-Wilczkiewicz, A.; Kalinowski, D.S.; Musiol, R.; Finster, J.; Szurko, A.; Serafin, K.; Knas, M.; Kamalapuram, S.K.; Kovacevic, Z.; Jampilek, J.; Ratuszna, A.; Rzeszowska-Wolny, J.; Richardson, D.R.; Polanski, J. Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones. Bioorg. Med. Chem., 2010, 18(7), 2664-2671.
[http://dx.doi.org/10.1016/j.bmc.2010.02.025 ] [PMID: 20303768]
[9]
Bossù, E.; Aglianò, A.M.; Desideri, N.; Sestili, I.; Porrà, R.; Grandilone, M.; Quaglia, M.G. LTB4 as marker of 5-LO inhibitory activity of two new N-ω-ethoxycarbonyl-4-quinolones. J. Pharm. Biomed. Anal., 1999, 19(3-4), 539-548.
[http://dx.doi.org/10.1016/S0731-7085(98)00250-7 ] [PMID: 10704120]
[10]
Sissi, C.; Palumbo, M. The quinolone family: From antibacterial to anticancer agents. Curr. Med. Chem. Anticancer Agents, 2003, 3(6), 439-450.
[http://dx.doi.org/10.2174/1568011033482279 ] [PMID: 14529452]
[11]
Jampilek, J.; Dolezal, M.; Opletalova, V.; Hartl, J. 5-Lipoxygenase, leukotrienes biosynthesis and potential antileukotrienic agents. Curr. Med. Chem., 2006, 13(2), 117-129.
[http://dx.doi.org/10.2174/092986706775197935 ] [PMID: 16472209]
[12]
Jampilek, J.; Dolezal, M.; Kunes, J.; Víchova, P.; Raich, I.; Jun, D.; O’Connor, R.; Clynes, M. Preparation of 2-(4-[4-(quinolin-2-ylmethoxy) phenyl] sulfanyl phenyl) propionic acid (VUFB 20615) and 2-methyl-2-(4-[4-(quinolin-2-ylmethoxy) phenyl] sulfanyl phenyl) propionic acid (VUFB 20623) as potential antileukotrienic agents. Curr. Org. Chem., 2004, 8, 1235-1243.
[http://dx.doi.org/10.2174/1385272043370041]
[13]
Vangapandu, S.; Jain, M.; Jain, R.; Kaur, S.; Singh, P.P. Ring-substituted quinolines as potential anti-tuberculosis agents. Bioorg. Med. Chem., 2004, 12(10), 2501-2508.
[http://dx.doi.org/10.1016/j.bmc.2004.03.045 ] [PMID: 15110831]
[14]
Chang, F.S.; Chen, W.; Wang, C.; Tzeng, C.C.; Chen, Y.L. Synthesis and antiproliferative evaluations of certain 2-phenylvinylquinoline (2-styrylquinoline) and 2-furanylvinylquinoline derivatives. Bioorg. Med. Chem., 2010, 18(1), 124-133.
[http://dx.doi.org/10.1016/j.bmc.2009.11.012 ] [PMID: 19944612]
[15]
Zhao, Y.L.; Chen, Y.L.; Chang, F.S.; Tzeng, C.C. Synthesis and cytotoxic evaluation of certain 4-anilino-2-phenylquinoline derivatives. Eur. J. Med. Chem., 2005, 40(8), 792-797.
[http://dx.doi.org/10.1016/j.ejmech.2005.03.008 ] [PMID: 16122581]
[16]
Zhao, Y.L.; Chen, Y.L.; Tzeng, C.C.; Chen, I.L.; Wang, T.C.; Han, C.H. Synthesis and cytotoxic evaluation of certain 4-(phenylamino) furo[2,3-b]quinoline and 2-(furan-2-yl)-4-(phenylamino)quinoline derivatives. Chem. Biodivers., 2005, 2(2), 205-214.
[http://dx.doi.org/10.1002/cbdv.200590003 ] [PMID: 17191973]
[17]
Chen, Y.L.; Huang, C.J.; Huang, Z.Y.; Tseng, C.H.; Chang, F.S.; Yang, S.H.; Lin, S.R.; Tzeng, C.C. Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives. Bioorg. Med. Chem., 2006, 14(9), 3098-3105.
[http://dx.doi.org/10.1016/j.bmc.2005.12.017 ] [PMID: 16412647]
[18]
Chen, Y.L.; Zhao, Y.L.; Lu, C.M.; Tzeng, C.C.; Wang, J.P. Synthesis, cytotoxicity, and anti-inflammatory evaluation of 2-(furan-2-yl)-4-(phenoxy)quinoline derivatives. Part 4. Bioorg. Med. Chem., 2006, 14(13), 4373-4378.
[http://dx.doi.org/10.1016/j.bmc.2006.02.039 ] [PMID: 16524734]
[19]
Behforouz, M.; Cai, W.; Stocksdale, M.G.; Lucas, J.S.; Jung, J.Y.; Briere, D.; Wang, A.; Katen, K.S.; Behforouz, N.C. Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors: Synthesis and evaluation of anti-reverse transcriptase activity of amide and ester analogues of lavendamycin. J. Med. Chem., 2003, 46(26), 5773-5780.
[http://dx.doi.org/10.1021/jm0304414 ] [PMID: 14667230]
[20]
Behforouz, M.; Cai, W.; Mohammadi, F.; Stocksdale, M.G.; Gu, Z.; Ahmadian, M.; Baty, D.E.; Etling, M.R.; Al-Anzi, C.H.; Swiftney, T.M.; Tanzer, L.R.; Merriman, R.L.; Behforouz, N.C. Synthesis and evaluation of antitumor activity of novel N-acyllavendamycin analogues and quinoline-5,8-diones. Bioorg. Med. Chem., 2007, 15(1), 495-510.
[http://dx.doi.org/10.1016/j.bmc.2006.09.039 ] [PMID: 17035024]
[21]
Behforouz, M.; Haddad, J.; Cai, W.; Arnold, M.B.; Mohammadi, F.; Sousa, A.C.; Horn, M.A. Highly efficient and practical syntheses of lavendamycin methyl ester and related novel quinolindiones. J. Org. Chem., 1996, 61(19), 6552-6555.
[http://dx.doi.org/10.1021/jo960794t ] [PMID: 11667519]
[22]
Fang, Y.; Linardic, C.M.; Richardson, D.A.; Cai, W.; Behforouz, M.; Abraham, R.T. Characterization of the cytotoxic activities of novel analogues of the antitumor agent, lavendamycin. Mol. Cancer Ther., 2003, 2(6), 517-526.
[23]
Podeszwa, B.; Niedbala, H.; Polanski, J.; Musiol, R.; Tabak, D.; Finster, J.; Serafin, K.; Milczarek, M.; Wietrzyk, J.; Boryczka, S.; Mol, W.; Jampilek, J.; Dohnal, J.; Kalinowski, D.S.; Richardson, D.R. Investigating the antiproliferative activity of quinoline-5,8-diones and styrylquinolinecarboxylic acids on tumor cell lines. Bioorg. Med. Chem. Lett., 2007, 17(22), 6138-6141.
[http://dx.doi.org/10.1016/j.bmcl.2007.09.040 ] [PMID: 17904844]
[24]
Tsotinis, A.; Vlachou, M.; Gerasimopoulou, M.; Eikosipentaki, A.; Ioannidis, C.; Klouvidaki, A.; Afroudakis, P.; Moreau, D.; Roussakis, C. Symmetrical derivatives of C2-substituted pyrrolo [2, 3-f] quinolines: Synthesis, cytotoxicity and drug delivery studies. Lett. Drug Des. Discov., 2007, 4, 87-91.
[http://dx.doi.org/10.2174/157018007779422488]
[25]
Mrozek-Wilczkiewicz, A.; Spaczynska, E.; Malarz, K.; Cieslik, W.; Rams-Baron, M.; Kryštof, V.; Musiol, R. Design, synthesis and in vitro activity of anticancer styrylquinolines. The p53 independent mechanism of action. PLoS One, 2015, 10(11)e0142678
[PMID: 26599982] [http://dx.doi.org/10.1371/journal.pone.0142678]
[26]
Al-ghamdi, A.M.; Hassan, A.; Abd, F.; Mohamed, H.M.; El-agrody, A.M. Synthesis and antitumor activities of 4H-pyrano [3, 2-h] quinoline-3-carbonitrile, 7H-Pyrimido [4′, 5′: 6, 5] pyrano [3, 2-h] quinoline, and 14HPyrimido [4′, 5′: 6, 5] pyrano [3, 2-h][1, 2, 4] triazolo [1, 5-c] quinoline derivatives. Lett. Drug Des. Discov., 2012, 561, 459-470.
[http://dx.doi.org/10.2174/157018012800389331]
[27]
Ma, X.H.; Zhang, X.Y.; Tan, J.J.; Chen, W.Z.; Wang, C.X. Exploring binding mode for styrylquinoline HIV-1 integrase inhibitors using comparative molecular field analysis and docking studies. Acta Pharmacol. Sin., 2004, 25(7), 950-958.
[PMID: 15210071]
[28]
Musiol, R. Styrylquinoline - A versatile scaffold in medicinal chemistry. Med. Chem., 2020, 16(2), 141-154.
[http://dx.doi.org/10.2174/1573406415666190603103012 ] [PMID: 31161997]
[29]
Narender, P.; Srinivas, U.; Ravinder, M.; Rao, B.A.; Ramesh, Ch.; Harakishore, K.; Gangadasu, B.; Murthy, U.S.N.; Rao, V.J. Synthesis of multisubstituted quinolines from Baylis-Hillman adducts obtained from substituted 2-chloronicotinaldehydes and their antimicrobial activity. Bioorg. Med. Chem., 2006, 14(13), 4600-4609.
[http://dx.doi.org//10.1016/j.bmc.2006.02.020] [PMID: 16510289]
[30]
Wang, G.W.; Jia, C.S.; Dong, Y.W. Benign and highly efficient synthesis of quinolines from 2-aminoarylketone or 2-aminoarylaldehyde and carbonyl compounds mediated by hydrochloric acid in water. Tetrahedron Lett., 2006, 47, 1059-1063.
[http://dx.doi.org/10.1016/j.tetlet.2005.12.05]
[31]
Kumar, D.; Kumar, A.; Qadri, M.M.; Ansari, M.I.; Gautam, A.; Chakraborti, A.K. In (OTf) 3-catalyzed synthesis of 2-styryl quinolines: Scope and limitations of metal Lewis acids for tandem Friedländer annulation-Knoevenagel condensation. RSC Advances, 2015, 5, 2920-2927.
[http://dx.doi.org/10.1039/C4RA10613J]
[32]
Shah, T.; Joshi, K.; Mishra, S.; Otiv, S.; Kumbar, V. Molecular and cellular effects of vitamin B12 forms on human trophoblast cells in presence of excessive folate. Biomed. Pharmacother., 2016, 84, 526-534.
[http://dx.doi.org/10.1016/j.biopha.2016.09.071 ] [PMID: 27693961]
[33]
Bhat, S.S.; Revankar, V.K.; Kumbar, V.; Bhat, K.; Kawade, V.A. Synthesis, crystal structure and biological properties of a cis-dichloridobis(diimine)copper(II) complex. Acta Crystallogr. C Struct. Chem., 2018, 74(Pt 2), 146-151.
[http://dx.doi.org/10.1107/S2053229617018551 ] [PMID: 29400328]
[34]
Ashkenazi, A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat. Rev. Cancer, 2002, 2(6), 420-430.
[http://dx.doi.org/10.1038/nrc821 ] [PMID: 12189384]
[35]
Ghobrial, I.M.; Witzig, T.E.; Adjei, A.A. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin., 2005, 55(3), 178-194.
[http://dx.doi.org/10.3322/canjclin.55.3.178 ] [PMID: 15890640]
[36]
Debatin, K.M. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol. Immunother., 2004, 53(3), 153-159.
[http://dx.doi.org/10.1007/s00262-003-0474-8 ] [PMID: 14749900]
[37]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0 ] [PMID: 11259830]
[38]
Veber, D.F.; Johnson, S.R.; Cheng, H-Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem., 2002, 45(12), 2615-2623.
[http://dx.doi.org/10.1021/jm020017n ] [PMID: 12036371]
[39]
VCCLAB Virtual Computational Chemistry Laboratory. http://www.vcclab.org2016.
[40]
Bickerton, G.R.; Paolini, G.V.; Besnard, J.; Muresan, S.; Hopkins, A.L. Quantifying the chemical beauty of drugs. Nat. Chem., 2012, 4(2), 90-98.
[http://dx.doi.org/10.1038/nchem.1243 ] [PMID: 22270643]
[41]
Ahsan, M.J.; Samy, J.G.; Khalilullah, H.; Nomani, M.S.; Saraswat, P.; Gaur, R.; Singh, A. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21(24), 7246-7250.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.057 ] [PMID: 22071303]
[42]
Rajanarendar, E.; Rama Krishna, S.; Nagaraju, D.; Govardhan Reddy, K.; Kishore, B.; Reddy, Y.N. Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons. Bioorg. Med. Chem. Lett., 2015, 25(7), 1630-1634.
[http://dx.doi.org/10.1016/j.bmcl.2015.01.041 ] [PMID: 25708616]
[43]
The logarithm of the octanol/water partition coefficient. http://www.asteris-app.com/technical-info/core-properties/logp.htm2016.
[44]
Cheng, F.; Li, W.; Zhou, Y.; Shen, J.; Wu, Z.; Liu, G.; Lee, P.W.; Tang, Y. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J. Chem. Inf. Model., 2012, 52(11), 3099-3105.
[http://dx.doi.org/10.1021/ci300367a ] [PMID: 23092397]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy