Exploring the Therapeutic Marvels: A Comprehensive Review on the
Biological Potential of Quinoline-5,8-Dione

Neetu      Agrawal; Dimple      Bansal; Shilpi      Pathak

doi:10.2174/0115734064287677231215070816

Abstract

Quinoline-5,8-diones, also referred to as 5,8-quinolinediones or quinolinequinones, have been researched extensively for their antiproliferative effects, where they displayed great results. Other than anticancer, they exhibit multiple activities such as antimalarial, antiviral, antibacterial, and antifungal activities. Natural quinolinequinones have also been known for their significant activities. The review highlights the diverse biological activities exhibited by synthetic quinoline- 5,8-diones over the past two decades. Continued research in this field is warranted to fully exploit the therapeutic potential of these intriguing compounds and their derivatives for future drug development. By comprehensively evaluating the therapeutic applications and biological activities of quinoline-5,8-dione derivatives, this review endeavors to provide researchers and practitioners with a valuable resource that will foster informed decision-making and inspire further investigations into harnessing the immense potential of this intriguing scaffold for the benefit of human health.

Keywords: Quinoline-5, 8-dione, biological activity, anticancer, heterocycle, natural antibiotics, quinolinequinones.

« Previous Next »

Graphical Abstract

[1]
Lanfranchi, D.A.; Cesar-Rodo, E.; Bertrand, B.; Huang, H.H.; Day, L.; Johann, L.; Elhabiri, M.; Becker, K.; Williams, D.L.; Davioud-Charvet, E. Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents. Org. Biomol. Chem.,  2012, 10(31), 6375-6387.
 [http://dx.doi.org/10.1039/c2ob25812a] [PMID: 22777178]

[2]
Bringmann, G.; Reichert, Y.; Kane, V.V. The total synthesis of streptonigrin and related antitumor antibiotic natural products. Tetrahedron,  2004, 60(16), 3539-3574.
 [http://dx.doi.org/10.1016/j.tet.2004.02.060]

[3]
Cai, W.; Hassani, M.; Karki, R.; Walter, E.D.; Koelsch, K.H.; Seradj, H.; Lineswala, J.P.; Mirzaei, H.; York, J.S.; Olang, F.; Sedighi, M.; Lucas, J.S.; Eads, T.J.; Rose, A.S.; Charkhzarrin, S.; Hermann, N.G.; Beall, H.D.; Behforouz, M. Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. Bioorg. Med. Chem.,  2010, 18(5), 1899-1909.
 [http://dx.doi.org/10.1016/j.bmc.2010.01.037] [PMID: 20149966]

[4]
Chan, B.K.; Ciufolini, M.A. Total synthesis of streptonigrone. J. Org. Chem.,  2007, 72(22), 8489-8495.
 [http://dx.doi.org/10.1021/jo701435p] [PMID: 17910501]

[5]
Pearce, A.N.; Chia, E.W.; Berridge, M.V.; Clark, G.R.; Harper, J.L.; Larsen, L.; Maas, E.W.; Page, M.J.; Perry, N.B.; Webb, V.L.; Copp, B.R. Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: Inhibitors of the neutrophil respiratory burst in a model of gouty arthritis. J. Nat. Prod.,  2007, 70(6), 936-940.
 [http://dx.doi.org/10.1021/np060626o] [PMID: 17497807]

[6]
Kadela-Tomanek, M.; Pawełczak, B.; Jastrzębska, M.; Bębenek, E.; Chrobak, E.; Latocha, M.; Kusz, J.; Książek, M.; Boryczka, S. Structural, vibrational and quantum chemical investigations for 6,7-dichloro-2-methyl-5,8-quinolinedione. Cytotoxic and molecular docking studies. J. Mol. Struct.,  2018, 1168, 73-83.
 [http://dx.doi.org/10.1016/j.molstruc.2018.05.031]

[7]
Hsu, T.S.; Chen, C.; Lee, P.T.; Chiu, S.J.; Liu, H.F.; Tsai, C.C.; Chao, J.I. 7-Chloro-6-piperidin-1-yl-quinoline-5,8-dione (PT-262), a novel synthetic compound induces lung carcinoma cell death associated with inhibiting ERK and CDC2 phosphorylation via a p53-independent pathway. Cancer Chemother. Pharmacol.,  2008, 62(5), 799-808.
 [http://dx.doi.org/10.1007/s00280-007-0667-5] [PMID: 18193228]

[8]
Brisson, M.; Nguyen, T.; Wipf, P.; Joo, B.; Day, B.W.; Skoko, J.S.; Schreiber, E.M.; Foster, C.; Bansal, P.; Lazo, J.S. Redox regulation of Cdc25B by cell-active quinolinediones. Mol. Pharmacol.,  2005, 68(6), 1810-1820.
 [http://dx.doi.org/10.1124/mol.105.016360] [PMID: 16155209]

[9]
Santoso, K.T.; Menorca, A.; Cheung, C.Y.; Cook, G.M.; Stocker, B.L.; Timmer, M.S.M. The synthesis and evaluation of quinolinequinones as anti-mycobacterial agents. Bioorg. Med. Chem.,  2019, 27(16), 3532-3545.
 [http://dx.doi.org/10.1016/j.bmc.2019.06.002] [PMID: 31262663]

[10]
Alfadhli, A.; Mack, A.; Harper, L.; Berk, S.; Ritchie, C.; Barklis, E. Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties. Bioorg. Med. Chem.,  2016, 24(21), 5618-5625.
 [http://dx.doi.org/10.1016/j.bmc.2016.09.028] [PMID: 27663546]

[11]
Lim, K.M.; Lee, J.Y.; Lee, S.M.; Bae, O.N.; Noh, J.Y.; Kim, E.J.; Chung, S.M.; Chung, J.H. Potent anti‐inflammatory effects of two quinolinedione compounds, OQ1 and OQ21, mediated by dual inhibition of inducible NO synthase and cyclooxygenase‐2. Br. J. Pharmacol.,  2009, 156(2), 328-337.
 [http://dx.doi.org/10.1111/j.1476-5381.2008.00028.x] [PMID: 19154436]

[12]
Hussain, H.; Specht, S.; Sarite, S.R.; Hoerauf, A.; Krohn, K. New quinoline-5,8-dione and hydroxynaphthoquinone derivatives inhibit a chloroquine resistant Plasmodium falciparum strain. Eur. J. Med. Chem.,  2012, 54, 936-942.
 [http://dx.doi.org/10.1016/j.ejmech.2012.06.046] [PMID: 22781704]

[13]
Kadela-Tomanek, M.; Bębenek, E.; Chrobak, E.; Boryczka, S. 5,8-Quinolinedione scaffold as a promising moiety of bioactive agents. Molecules,  2019, 24(22), 4115.
 [http://dx.doi.org/10.3390/molecules24224115] [PMID: 31739496]

[14]
Suh, M.; Park, S.; Lee, C. Quinoline-5, 8-dione derivatives and evaluation on their cytotoxic activity. 2001, 9, 2979-2986.

[15]
Mulchin, B.J.; Newton, C.G.; Baty, J.W.; Grasso, C.H.; Martin, W.J.; Walton, M.C.; Dangerfield, E.M.; Plunkett, C.H.; Berridge, M.V.; Harper, J.L.; Timmer, M.S.M.; Stocker, B.L. The anti-cancer, anti-inflammatory and tuberculostatic activities of a series of 6,7-substituted-5,8-quinolinequinones. Bioorg. Med. Chem.,  2010, 18(9), 3238-3251.
 [http://dx.doi.org/10.1016/j.bmc.2010.03.021] [PMID: 20363637]

[16]
Nepali, K.; Kumar, S.; Huang, H.L.; Kuo, F.C.; Lee, C.H.; Kuo, C.C.; Yeh, T.K.; Li, Y.H.; Chang, J.Y.; Liou, J.P.; Lee, H.Y. 2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition. Org. Biomol. Chem.,  2016, 14(2), 716-723.
 [http://dx.doi.org/10.1039/C5OB02100F] [PMID: 26694589]

[17]
Chaaban, I.; Hafez, H.; AlZaim, I.; Tannous, C.; Ragab, H.; Hazzaa, A.; Ketat, S.; Ghoneim, A.; Katary, M.; Abd-Alhaseeb, M.M.; Zouein, F.A.; Albohy, A.; Amer, A.N.; El-Yazbi, A.F.; Belal, A.S.F. Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis. Bioorg. Chem.,  2021, 113, 105035.
 [http://dx.doi.org/10.1016/j.bioorg.2021.105035] [PMID: 34091287]

[18]
Li, Z.; Zhou, J.; Gan, Y.; Yin, Y.; Zhang, W.; Yang, J.; Tang, Y.; Dai, Y. Synthesis of a novel platinum(II) complex with 6,7-dichloro-5,8-quinolinedione and the study of its antitumor mechanism in testicular seminoma. J. Inorg. Biochem.,  2019, 197, 110701.
 [http://dx.doi.org/10.1016/j.jinorgbio.2019.110701] [PMID: 31055215]

[19]
Ling, Y.; Yang, Q.X.; Teng, Y.N.; Chen, S.; Gao, W.J.; Guo, J.; Hsu, P.L.; Liu, Y.; Morris-Natschke, S.L.; Hung, C.C.; Lee, K.H. Development of novel amino-quinoline-5,8-dione derivatives as NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors with potent antiproliferative activities. Eur. J. Med. Chem.,  2018, 154, 199-209.
 [http://dx.doi.org/10.1016/j.ejmech.2018.05.025] [PMID: 29803003]

[20]
Lazo, J.S.; Aslan, D.C.; Southwick, E.C.; Cooley, K.A.; Ducruet, A.P.; Joo, B.; Vogt, A.; Wipf, P. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25. J. Med. Chem.,  2001, 44(24), 4042-4049.
 [http://dx.doi.org/10.1021/jm0102046] [PMID: 11708908]

[21]
Pu, L.; Amoscato, A.A.; Bier, M.E.; Lazo, J.S. Dual G1 and G2 phase inhibition by a novel, selective Cdc25 inhibitor 6-chloro-7-[corrected](2-morpholin-4-ylethylamino)-quinoline-5,8-dione. J. Biol. Chem.,  2002, 277(49), 46877-46885.
 [http://dx.doi.org/10.1074/jbc.M207902200] [PMID: 12356752]

[22]
Keyari, C.M.; Kearns, A.K.; Duncan, N.S.; Eickholt, E.A.; Abbott, G.; Beall, H.D.; Diaz, P. Synthesis of new quinolinequinone derivatives and preliminary exploration of their cytotoxic properties. J. Med. Chem.,  2013, 56(10), 3806-3819.
 [http://dx.doi.org/10.1021/jm301689x] [PMID: 23574193]

[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]
Ciftci, H.I.; Bayrak, N.; Yıldız, M.; Yıldırım, H.; Sever, B.; Tateishi, H.; Otsuka, M.; Fujita, M.; Tuyun, A.F. Design, synthesis and investigation of the mechanism of action underlying anti-leukemic effects of the quinolinequinones as LY83583 analogs. Bioorg. Chem.,  2021, 114, 105160.
 [http://dx.doi.org/10.1016/j.bioorg.2021.105160] [PMID: 34328861]

[25]
Bayrak, N.; Ciftci, H.I.; Yıldız, M.; Yıldırım, H.; Sever, B.; Tateishi, H.; Otsuka, M.; Fujita, M.; Tuyun, A.F. Structure based design, synthesis, and evaluation of anti-CML activity of the quinolinequinones as LY83583 analogs. Chem. Biol. Interact.,  2021, 345, 109555.
 [http://dx.doi.org/10.1016/j.cbi.2021.109555] [PMID: 34146539]

[26]
Jannuzzi, A.T.; Yilmaz Goler, A.M.; Shilkar, D.; Mondal, S.; Basavanakatti, V.N.; Yıldırım, H.; Yıldız, M.; Çelik Onar, H.; Bayrak, N.; Jayaprakash, V. TuYuN, A.F. Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling. In: Chem. Biol. Drug Des.,  2023, 102(5), 1133-1154.

[27]
Hargreaves, R.; David, C.L.; Whitesell, L.; Skibo, E.B. Design of quinolinedione-Based geldanamycin analogues. Bioorg. Med. Chem. Lett.,  2003, 13(18), 3075-3078.
 [http://dx.doi.org/10.1016/S0960-894X(03)00650-4] [PMID: 12941337]

[28]
Hargreaves, R.H.J.; David, C.L.; Whitesell, L.J.; LaBarbera, D.V.; Jamil, A.; Chapuis, J.C.; Skibo, E.B. Discovery of quinolinediones exhibiting a heat shock response and angiogenesis inhibition. J. Med. Chem.,  2008, 51(8), 2492-2501.
 [http://dx.doi.org/10.1021/jm7014099] [PMID: 18363347]

[29]
Modranka, J.; Drogosz-Stachowicz, J.; Pietrzak, A.; Janecka, A.; Janecki, T. Synthesis and structure–activity relationship study of novel 3-diethoxyphosphorylfuroquinoline-4,9-diones with potent antitumor efficacy. Eur. J. Med. Chem.,  2021, 219, 113429.
 [http://dx.doi.org/10.1016/j.ejmech.2021.113429] [PMID: 33852973]

[30]
Kadela, M.; Jastrzębska, M.; Bębenek, E.; Chrobak, E.; Latocha, M.; Kusz, J.; Książek, M.; Boryczka, S.; Mayence, A. Synthesis, structure and cytotoxic activity of mono- and dialkoxy derivatives of 5,8-quinolinedione. Molecules,  2016, 21(2), 156.
 [http://dx.doi.org/10.3390/molecules21020156] [PMID: 26828467]

[31]
Kadela-Tomanek, M.; Bębenek, E.; Chrobak, E.; Latocha, M.; Boryczka, S. Alkoxy and enediyne derivatives containing 1,4-benzoquinone subunits—synthesis and antitumor activity. Molecules,  2017, 22(3), 447.
 [http://dx.doi.org/10.3390/molecules22030447] [PMID: 28287461]

[32]
Kadela-Tomanek, M.; Jastrzębska, M.; Bębenek, E.; Chrobak, E.; Latocha, M.; Kusz, J.; Tarnawska, D.; Boryczka, S. New acetylenic amine derivatives of 5,8-quinolinediones: Synthesis, crystal structure and antiproliferative activity. Crystals,  2017, 7(1), 15.
 [http://dx.doi.org/10.3390/cryst7010015]

[33]
Kadela-Tomanek, M.; Jastrzębska, M.; Pawełczak, B.; Bębenek, E.; Chrobak, E.; Latocha, M.; Książek, M.; Kusz, J.; Boryczka, S. Alkynyloxy derivatives of 5,8-quinolinedione: Synthesis, in vitro cytotoxicity studies and computational molecular modeling with NAD(P)H:Quinone oxidoreductase 1. Eur. J. Med. Chem.,  2017, 126, 969-982.
 [http://dx.doi.org/10.1016/j.ejmech.2016.12.031] [PMID: 28006669]

[34]
Kadela-Tomanek, M.; Jastrzębska, M.; Marciniec, K.; Chrobak, E.; Bębenek, E.; Latocha, M.; Kuśmierz, D.; Boryczka, S. Design, synthesis and biological activity of 1,4-quinone moiety attached to betulin derivatives as potent DT-diaphorase substrate. Bioorg. Chem.,  2021, 106, 104478.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104478] [PMID: 33272711]

[35]
Dreyton, C.J.; Anderson, E.D.; Subramanian, V.; Boger, D.L.; Thompson, P.R. Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation. Bioorg. Med. Chem.,  2014, 22(4), 1362-1369.
 [http://dx.doi.org/10.1016/j.bmc.2013.12.064] [PMID: 24440480]

[36]
Ezugwu, J.A.; Ezeokonkwo, M.A.; Okafor, S.N.; Godwin-nwakwasi, E.U. Palladium-Catalyzed Sonogashira Synthesis of Alkynyl Derivatives of Quinoline-5, 8-Dione. 2017, 5, 1137-1144.

[37]
Chemistry, I.; State, E.; State, E.; State, A.; State, E. Double Alkynylation of quinoline-5, 8-diones and their in-silico and antimicrobial studies; , 2018.  Available from:
 [http://dx.doi.org/10.4314/Jasem.V22i7.20]

[38]
Ezeokonkwo, M.A.; Ibeanu, F.N.; Eze, C.; Ibezim, A.; Ezeokoye, C.; Ezenwa, O.I.; Ezeoka, T.V.; Vincent, O.A. Synthesis, antimicrobial activity and molecular docking studies of 7-bromoquinoline-5,8-dione containing aryl sulphonamides. Int. J. Appl. Chem.,  2019, 15, 99-112.

Rights & Permissions Print Cite

Article Metrics

24

2

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0115734064287677231215070816	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638

Medicinal Chemistry

Exploring the Therapeutic Marvels: A Comprehensive Review on the Biological Potential of Quinoline-5,8-Dione

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles