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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Cinchonine: A Versatile Pharmacological Agent Derived from Natural Cinchona Alkaloids

Author(s): Shahnaz Parveen, Nidhi Maurya, Abha Meena and Suaib Luqman*

Volume 24, Issue 4, 2024

Published on: 27 November, 2023

Page: [343 - 363] Pages: 21

DOI: 10.2174/0115680266270796231109171808

Price: $65

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Abstract

Background: Cinchonine is one of the Cinchona alkaloids that is commercially extracted from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra, and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine has been historically used as an anti-malarial agent. It also has a wide range of other biological properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial, anti-platelet aggregation, and anti-osteoclast differentiation.

Aim and Objective: This review discusses the pharmacological activity of cinchonine under different experimental conditions, including in silico, in vitro, and in vivo. It also covers the compound's physicochemical properties, toxicological aspects, and pharmacokinetics.

Methodology: A comprehensive literature search was conducted on multiple online databases, such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research papers and bibliographic sources. The process involved applying exclusion and inclusion criteria to ensure the selection of relevant and high-quality papers.

Results: Cinchonine has numerous pharmacological properties, making it a promising compound for various therapeutic applications. It induces anti-cancer activity by activating caspase-3 and PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes the phosphorylation of PERK and ETIF-2α. Cinchonine also inhibits osteoclastogenesis, inhibiting TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-κB. Its potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting obesity-related diseases. However, research on cinchonine is limited, and further studies are needed to fully understand its therapeutic potential. Further investigation is needed to ensure its safety and efficacy in clinical applications.

Conclusion: Overall, this review article explains the pharmacological activity of cinchonine, its synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics.

Keywords: Cinchona officinalis, Alkaloids, Cinchonine, Anti-cancer, Anti-malarial, Anti-obesity.

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[1]
Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The traditional medicine and modern medicine from natural products. Molecules, 2016, 21(5), 559.
[http://dx.doi.org/10.3390/molecules21050559] [PMID: 27136524]
[2]
Zheng, Y.; Zhang, W.; Xu, L.; Zhou, H.; Yuan, M.; Xu, H. Recent progress in understanding the action of natural compounds at novel therapeutic drug targets for the treatment of liver cancer. Front. Oncol., 2022, 11, 795548.
[http://dx.doi.org/10.3389/fonc.2021.795548] [PMID: 35155196]
[3]
Jensen, K.; Jensen, P.E.; Møller, B.L. Light-driven cytochrome p450 hydroxylations. ACS Chem. Biol., 2011, 6(6), 533-539.
[http://dx.doi.org/10.1021/cb100393j] [PMID: 21323388]
[4]
Li, G.; Lou, H.X. Strategies to diversify natural products for drug discovery. Med. Res. Rev., 2018, 38(4), 1255-1294.
[http://dx.doi.org/10.1002/med.21474] [PMID: 29064108]
[5]
Dey, P.; Kundu, A.; Kumar, A.; Gupta, M.; Lee, B.M.; Bhakta, T.; Dash, S.; Kim, H.S. Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids). In: Recent Advances in Natural Products Analysis; , 2020; pp. 505-567.
[6]
Roy, S.; Ghorai, A.; Komber, H.; Voit, B.; Banerjee, S. Synthesis of 2,2′-hindered pyridine containing semifluorinated polytriazoles and investigation for low-temperature proton exchange membrane application with enhanced oxidative stability. Eur. Polym. J., 2020, 136, 109898.
[http://dx.doi.org/10.1016/j.eurpolymj.2020.109898]
[7]
Verma, A.K.; Dubbu, S.; Chennaiah, A.; Vankar, Y.D. Synthesis of di- and trihydroxy proline derivatives from D-glycals: Application in the synthesis of polysubstituted pyrrolizidines and bioactive 1C-aryl/alkyl pyrrolidines. Carbohydr. Res., 2019, 475, 48-55.
[http://dx.doi.org/10.1016/j.carres.2019.02.004] [PMID: 30825721]
[8]
Costa, R.S.; Souza Filho, O.P.; Júnior, O.C.S.D.; Silva, J.J.; Hyaric, M.L.; Santos, M.A.V.; Velozo, E.S. In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba. Rev. Bras. Farmacogn., 2018, 28(5), 551-558.
[http://dx.doi.org/10.1016/j.bjp.2018.04.013]
[9]
Sandenon Seteyen, A.L.; Girard-Valenciennes, E.; Septembre-Malaterre, A.; Gasque, P.; Guiraud, P.; Sélambarom, J. Anti-alphaviral alkaloids: Focus on some isoquinolines, indoles and quinolizidines. Molecules, 2022, 27(16), 5080.
[http://dx.doi.org/10.3390/molecules27165080] [PMID: 36014321]
[10]
Shang, X.F.; Morris-Natschke, S.L.; Liu, Y.Q.; Guo, X.; Xu, X.S.; Goto, M.; Li, J.C.; Yang, G.Z.; Lee, K.H. Biologically active quinoline and quinazoline alkaloids part I. Med. Res. Rev., 2018, 38(3), 775-828.
[http://dx.doi.org/10.1002/med.21466] [PMID: 28902434]
[11]
Shakhidoyatov, K.M.; Elmuradov, B.Z. Tricyclic quinazoline alkaloids: Isolation, synthesis, chemical modification, and biological activity. Chem. Nat. Compd., 2014, 50(5), 781-800.
[http://dx.doi.org/10.1007/s10600-014-1086-6]
[12]
Yin, Q.; Liu, X.; Zhang, Z.; Lei, H.; Wu, B. Chemistry and bioactivities of alkaloids isolated from marine fungi (covering 2016-2022). Fitoterapia, 2023, 164, 105377.
[http://dx.doi.org/10.1016/j.fitote.2022.105377] [PMID: 36544299]
[13]
Zi, W.; Zuo, Z.; Ma, D. Intramolecular dearomative oxidative coupling of indoles: a unified strategy for the total synthesis of indoline alkaloids. Acc. Chem. Res., 2015, 48(3), 702-711.
[http://dx.doi.org/10.1021/ar5004303] [PMID: 25667972]
[14]
Aniszewski, T. Alkaloids: Chemistry, Biology, Ecology, and Applications; Elsevier, 2015.
[15]
Tuenter, E.; Exarchou, V.; Apers, S.; Pieters, L. Cyclopeptide alkaloids. Phytochem. Rev., 2017, 16(4), 623-637.
[http://dx.doi.org/10.1007/s11101-016-9484-y]
[16]
Swain, S.S.; Paidesetty, S.K.; Padhy, R.N. Antibacterial, antifungal and antimycobacterial compounds from cyanobacteria. Biomed. Pharmacother., 2017, 90, 760-776.
[http://dx.doi.org/10.1016/j.biopha.2017.04.030] [PMID: 28419973]
[17]
Ur Rashid, M.; Alamzeb, M.; Ali, S.; Ullah, Z.; Shah, Z.A.; Naz, I.; Khan, M.R. The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review. Phytother. Res., 2019, 33(10), 2661-2684.
[http://dx.doi.org/10.1002/ptr.6466] [PMID: 31453659]
[18]
Roy, A. A review on the alkaloids an important therapeutic compound from plants. Int. J. Plant Biotechnol., 2017, 3, 1-9.
[19]
Bribi, N. Pharmacological activity of alkaloids: A review. Asian J. Biol., 2018, 1, 1-6.
[20]
Roy, M.; Datta, A. Cancer Genetics and Therapeutics: Focus on Phytochemicals; Springer Nature, 2019.
[http://dx.doi.org/10.1007/978-981-13-9471-3]
[21]
Casciaro, B.; Mangiardi, L.; Cappiello, F.; Romeo, I.; Loffredo, M.R.; Iazzetti, A.; Calcaterra, A.; Goggiamani, A.; Ghirga, F.; Mangoni, M.L.; Botta, B.; Quaglio, D. Naturally-occurring alkaloids of plant origin as potential antimicrobials against antibiotic-resistant infections. Molecules, 2020, 25(16), 3619.
[http://dx.doi.org/10.3390/molecules25163619] [PMID: 32784887]
[22]
Thawabteh, A.; Juma, S.; Bader, M.; Karaman, D.; Scrano, L.; Bufo, S.; Karaman, R. The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins, 2019, 11(11), 656.
[http://dx.doi.org/10.3390/toxins11110656] [PMID: 31717922]
[23]
Habartová, K; Cahlíková, L; Řezáčová, M; Havelek, R. The biological activity of alkaloids from the amaryllidaceae: From cholinesterases inhibition to anticancer activity. Nat. Prod. Commun., 2016, 11(10), 1934578X1601101038.
[24]
Xu, D.; Xu, Z. Indole alkaloids with potential anticancer activity. Curr. Top. Med. Chem., 2020, 20(21), 1938-1949.
[http://dx.doi.org/10.2174/1568026620666200622150325] [PMID: 32568021]
[25]
Souto, A.L.; Tavares, J.F.; da Silva, M.S.; Diniz, M.F.F.M.; de Athayde-Filho, P.F.; Barbosa Filho, J.M. Anti-inflammatory activity of alkaloids: An update from 2000 to 2010. Molecules, 2011, 16(10), 8515-8534.
[http://dx.doi.org/10.3390/molecules16108515] [PMID: 21989312]
[26]
Shan, L.; Tyagi, A.; Chen, X.; Yan, P.; Oh, D.H. Potential anti-obesity effect of fermented adzuki beans and their untargeted metabolomics using UHPLC-QTOF-MS. Food Biosci., 2023, 52, 102380.
[http://dx.doi.org/10.1016/j.fbio.2023.102380]
[27]
Ay, E.B.; Açıkgöz, M.A.; Kocaman, B.; Mesci, S.; Kocaman, B.; Yıldırım, T. Zinc and phosphorus fertilization in Galanthus elwesii Hook: Changes in the total alkaloid, flavonoid, and phenolic content, and evaluation of anti-cancer, anti-microbial, and antioxidant activities. Sci. Hortic., 2023, 317, 112034.
[http://dx.doi.org/10.1016/j.scienta.2023.112034]
[28]
Nalli, Y.; Khajuria, V.; Gupta, S.; Arora, P.; Riyaz-Ul-Hassan, S.; Ahmed, Z.; Ali, A. Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities. Org. Biomol. Chem., 2016, 14(12), 3322-3332.
[http://dx.doi.org/10.1039/C6OB00267F] [PMID: 26947457]
[29]
Supong, K.; Thawai, C.; Supothina, S.; Auncharoen, P.; Pittayakhajonwut, P. Antimicrobial and anti-oxidant activities of quinoline alkaloids from Pseudomonas aeruginosa BCC76810. Phytochem. Lett., 2016, 17, 100-106.
[http://dx.doi.org/10.1016/j.phytol.2016.07.007]
[30]
Badri, S; Basu, VR A review on pharmacological activities of alkaloids. World J. Curr. Med. Pharm. Res., 2019, 2019, 230-234.
[31]
Chauhan, R.; Tripathi, A.; Chauhan, A.; Basniwal, R.K.; Ranjan, A.; Kumari, A.; Rajput, V.D.; Prazdnova, E.V.; Minkina, T.; Chauhan, S.C.; Jindal, T.; Prasad, R. Bioactive compounds from high altitude lake Arthrospira platensis HANL01: Antioxidant property, thermal stability and antibacterial assessment against multiple antibiotics resistant bacteria. Bioresour. Technol. Rep., 2023, 22, 101398.
[http://dx.doi.org/10.1016/j.biteb.2023.101398]
[32]
Bayih, A.G.; Folefoc, A.; Mohon, A.N.; Eagon, S.; Anderson, M.; Pillai, D.R. in vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin. Malar. J., 2016, 15(1), 579.
[http://dx.doi.org/10.1186/s12936-016-1625-7] [PMID: 27903279]
[33]
Rayees, S.; Satti, N.K.; Mehra, R.; Nargotra, A.; Rasool, S.; Sharma, A.; Sahu, P.K.; Rajnikant; Gupta, V.K.; Nepali, K.; Singh, G. Anti-asthmatic activity of azepino [2, 1-b] quinazolones, synthetic analogues of vasicine, an alkaloid from Adhatoda vasica. Med. Chem. Res., 2014, 23(9), 4269-4279.
[http://dx.doi.org/10.1007/s00044-014-0996-y]
[34]
Fu, M.; Zou, B.; An, K.; Yu, Y.; Tang, D.; Wu, J.; Xu, Y.; Ti, H. Anti-asthmatic activity of alkaloid compounds from Pericarpium Citri Reticulatae ( Citrus reticulata ‘Chachi’). Food Funct., 2019, 10(2), 903-911.
[http://dx.doi.org/10.1039/C8FO01753K] [PMID: 30694283]
[35]
Zaima, K.; Koga, I.; Iwasawa, N.; Hosoya, T.; Hirasawa, Y.; Kaneda, T.; Ismail, I.S.; Lajis, N.H.; Morita, H. Vasorelaxant activity of indole alkaloids from Tabernaemontana dichotoma. J. Nat. Med., 2013, 67(1), 9-16.
[http://dx.doi.org/10.1007/s11418-012-0638-y] [PMID: 22350216]
[36]
Ravishankara, M.N.; Shrivastava, N.; Padh, H.; Rajani, M. HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark and its marketed formulations. Planta Med., 2001, 67(3), 294-296.
[http://dx.doi.org/10.1055/s-2001-11995] [PMID: 11345710]
[37]
Sánchez-Viesca, F; Gómez, R. The mechanism of the oxido-degradation of the cinchona alkaloids. Am. J. Chem., 2022, 12(1), 18-21.
[38]
Insanu, M.; Aziz, S.; Fidrianny, I.; Hartati, R.; Elfahmi; Sukrasno; Ruslan Wirasutisna, K. Natural anthraquinonefrom the bark of Cinchona officinalis L. Rasayan J. Chem., 2019, 12(2), 519-522.
[http://dx.doi.org/10.31788/RJC.2019.1221831]
[39]
Bharadwaj, K.C.; Gupta, T.; Singh, R.M. Alkaloid group of Cinchona officinalis: Structural, synthetic, and medicinal aspects. In: Synthesis of Medicinal Agents from Plants; Tewari, A.; Tiwari, S., Eds.; Elsevier, 2018; pp. 205-227.
[http://dx.doi.org/10.1016/B978-0-08-102071-5.00009-X]
[40]
Murauer, A.; Ganzera, M. Quantitative determination of major alkaloids in Cinchona bark by Supercritical Fluid Chromatography. J. Chromatogr. A, 2018, 1554, 117-122.
[http://dx.doi.org/10.1016/j.chroma.2018.04.038] [PMID: 29699870]
[41]
Kacprzak, K. Chemistry and biology of cinchona alkaloids. In: Natural Products; Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes, 2013; pp. 605-641.
[http://dx.doi.org/10.1007/978-3-642-22144-6_22]
[42]
Oleksyn, B.J.; Suszko-Purzycka, A.; Dive, G.; Lamotte-Brasseur, J. Molecular properties of Cinchona alkaloids: A theoretical approach. J. Pharm. Sci., 1992, 81(2), 122-127.
[http://dx.doi.org/10.1002/jps.2600810204] [PMID: 1545349]
[43]
Warhurst, D.C.; Craig, J.C.; Adagu, I.S.; Meyer, D.J.; Lee, S.Y. The relationship of physico-chemical properties and structure to the differential antiplasmodial activity of the cinchona alkaloids. Malar. J., 2003, 2(1), 26.
[http://dx.doi.org/10.1186/1475-2875-2-26] [PMID: 14505493]
[44]
Khanifudin, A.; Primahana, G.; Prima, S.R.; Lotulung, P.D.; Hanafi, M. The synthesis of cinchonine tiglat ester compound and cytotoxic test against mcf-7 breast cancer cell. Jurnal Kimia Terapan Indonesia, 2018, 19(2), 54-61.
[http://dx.doi.org/10.14203/jkti.v19i2.354]
[45]
Genne, P.; Dimanche-Boitrel, M.T.; Mauvernay, R.Y.; Gutierrez, G.; Duchamp, O.; Petit, J.M.; Martin, F.; Chauffert, B. Cinchonine, a potent efflux inhibitor to circumvent anthracycline resistance in vivo. Cancer Res., 1992, 52(10), 2797-2801.
[PMID: 1581892]
[46]
Genne, P.; Duchamp, O.; Caillot, D.; Casasnovas, R.O.; Guy, H.; Dubrez, L.; Chauffert, B.; Solary, E. Preclinical study of cinchonine, a powerful MDR reversing agent. Anticancer Drugs, 1994, 5, 23.
[http://dx.doi.org/10.1097/00001813-199409001-00053]
[47]
Carroll, A.M.; Kavanagh, D.J.; McGovern, F.P.; Reilly, J.W.; Walsh, J.J. Nature’s chiral catalyst and anti-malarial agent: isolation and structure elucidation of cinchonine and quinine from Cinchona calisaya. J. Chem. Educ., 2012, 89(12), 1578-1581.
[http://dx.doi.org/10.1021/ed200713p]
[48]
Hidayat, I. Three quinine and cinchonidine producing fusarium species from Indonesia. Curr. Res. Environ. Appl. Mycol., 2016, 6(1), 20-34.
[http://dx.doi.org/10.5943/cream/6/1/3]
[49]
Canales, N.A.; Gress Hansen, T.N.; Cornett, C.; Walker, K.; Driver, F.; Antonelli, A.; Maldonado, C.; Nesbitt, M.; Barnes, C.J.; Rønsted, N. Historical chemical annotations of Cinchona bark collections are comparable to results from current day high-pressure liquid chromatography technologies. J. Ethnopharmacol., 2020, 249, 112375.
[http://dx.doi.org/10.1016/j.jep.2019.112375] [PMID: 31698039]
[50]
Gurung, P.; De, P. Spectrum of biological properties of cinchona alkaloids: A brief review. J. Pharmacogn. Phytochem., 2017, 6(4), 162-166.
[51]
Cheng, G.G.; Cai, X.H.; Zhang, B.H.; Li, Y.; Gu, J.; Bao, M.F.; Liu, Y.P.; Luo, X.D. Cinchona alkaloids from Cinchona succirubra and Cinchona ledgeriana. Planta Med., 2014, 80(02/03), 223-230.
[http://dx.doi.org/10.1055/s-0033-1360279] [PMID: 24452461]
[52]
Shibuya, H; Kitamura, C; Maehara, S; Nagahata, M; Winarno, H; Simanjuntak, P; Kim, HS; Wataya, Y; Ohashi, K Transformation of Cinchona alkaloids into 1-N-oxide derivatives by endophytic Xylaria sp isolated from Cinchona pubescens. Chem. Pharm. Bull., 2003, 51(1), 71-72.
[53]
Noriega, P.; Sola, M.; Barukcic, A.; Garcia, K.; Osorio, E. Cosmetic antioxidant potential of extracts from species of the cinchona pubescens (Vahl). Int. J. Phytocosmet. Nat. Ingred, 2015, 2(1), 14-14.
[http://dx.doi.org/10.15171/ijpni.2015.14]
[54]
Boratyński, P.J.; Zielińska-Błajet, M.; Skarżewski, J. Chapter Two - cinchona alkaloids-derivatives and applications. In: The Alkaloids: Chemistry and Biology; Knölker, H.J., Ed.; Academic Press, 2019; pp. 29-145.
[55]
Nyhlén, J.; Eriksson, L.; Bäckvall, J.E. Synthesis and optical resolution of an allenoic acid by diastereomeric salt formation induced by chiral alkaloids. Chirality, 2008, 20(1), 47-50.
[http://dx.doi.org/10.1002/chir.20479] [PMID: 17966123]
[56]
Isaac, J.E.; Robins, R.J.; Rhodes, M.J.C. Cinchoninone: Nadph oxidoreductases i and ii-novel enzymes in the biosynthesis of quinoline alkaloids in Cinchona ledgeriana. Phytochemistry, 1987, 26(2), 393-399.
[http://dx.doi.org/10.1016/S0031-9422(00)81420-X]
[57]
Geerlings, A.; Hallard, D.; Martinez Caballero, A.; Lopes Cardoso, I.; van der Heijden, R.; Verpoorte, R. Alkaloid production by a Cinchona officinalis ‘Ledgeriana’ hairy root culture containing constitutive expression constructs of tryptophan decarboxylase and strictosidine synthase cDNAs from Catharanthus roseus. Plant Cell Rep., 1999, 19(2), 191-196.
[http://dx.doi.org/10.1007/s002990050732] [PMID: 30754747]
[58]
Skinner, S.E.; Walton, N.J.; Robins, R.J.; Rhodes, M.J.C. Tryptophan decarboxylase strictosidine synthase and alkaloid production by Cinchona ledgeriana suspension cultures. Phytochemistry, 1987, 26(3), 721-725.
[http://dx.doi.org/10.1016/S0031-9422(00)84772-X]
[59]
Dugé de Bernonville, T.; Foureau, E.; Parage, C.; Lanoue, A.; Clastre, M.; Londono, M.A.; Oudin, A.; Houillé, B.; Papon, N.; Besseau, S.; Glévarec, G.; Atehortùa, L.; Giglioli-Guivarc’h, N.; St-Pierre, B.; De Luca, V.; O’Connor, S.E.; Courdavault, V. Characterization of a second secologanin synthase isoform producing both secologanin and secoxyloganin allows enhanced de novo assembly of a Catharanthus roseus transcriptome. BMC Genomics, 2015, 16(1), 619.
[http://dx.doi.org/10.1186/s12864-015-1678-y] [PMID: 26285573]
[60]
Irmler, S.; Schröder, G.; St-Pierre, B.; Crouch, N.P.; Hotze, M.; Schmidt, J.; Strack, D.; Matern, U.; Schröder, J. Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J., 2000, 24(6), 797-804.
[http://dx.doi.org/10.1046/j.1365-313x.2000.00922.x] [PMID: 11135113]
[61]
Treimer, J.F.; Zenk, M.H. Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation. Eur. J. Biochem., 1979, 101(1), 225-233.
[http://dx.doi.org/10.1111/j.1432-1033.1979.tb04235.x] [PMID: 510306]
[62]
Jin, Z.L.; Yan, W.; Qu, M.; Ge, C.Z.; Chen, X.; Zhang, S.F. Cinchonine activates endoplasmic reticulum stress-induced apoptosis in human liver cancer cells. Exp. Ther. Med., 2018, 15(6), 5046-5050.
[http://dx.doi.org/10.3892/etm.2018.6005] [PMID: 29805529]
[63]
Qi, Y.; Pradipta, A.R.; Li, M.; Zhao, X.; Lu, L.; Fu, X.; Wei, J.; Hsung, R.P.; Tanaka, K.; Zhou, L. Cinchonine induces apoptosis of HeLa and A549 cells through targeting TRAF6. J. Exp. Clin. Cancer Res., 2017, 36(1), 35.
[http://dx.doi.org/10.1186/s13046-017-0502-8] [PMID: 28231796]
[64]
Lee, S.Y.; Rhee, Y.H.; Jeong, S.J.; Lee, H.J.; Lee, H.J.; Jung, M.H.; Kim, S.H.; Lee, E.O.; Ahn, K.S.; Ahn, K.S.; Kim, S.H. Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel-induced cytotoxicity and apoptosis via multidrug resistance reversal in MES-SA/DX5 uterine sarcoma cells. Environ. Toxicol., 2011, 26(4), 424-431.
[http://dx.doi.org/10.1002/tox.20568] [PMID: 20196146]
[65]
Furusawa, S.; Nakano, S.; Wu, J.; Sakaguchi, S.; Takayanagi, M.; Sasaki, K.I.; Satoh, S. Apoptosis induced by doxorubicin and cinchonine in P388 multidrug-resistant cells. J. Pharm. Pharmacol., 2010, 53(7), 1029-1039.
[http://dx.doi.org/10.1211/0022357011776289] [PMID: 11480538]
[66]
Solary, E.; Mannone, L.; Moreau, D.; Caillot, D.; Casasnovas, R-O.; Guy, H.; Grandjean, M.; Wolf, J-E.; André, F.; Fenaux, P.; Canal, P.; Chauffert, B.; Wotawa, A.; Bayssas, M.; Genne, P. Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes. Leukemia, 2000, 14(12), 2085-2094.
[http://dx.doi.org/10.1038/sj.leu.2401945] [PMID: 11187897]
[67]
Wang, X.K.; Liao, X.W.; Huang, R.; Huang, J.L.; Chen, Z.J.; Zhou, X.; Yang, C.K.; Han, C.Y.; Zhu, G.Z.; Peng, T. Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma. J. Cancer, 2020, 11(20), 6140-6156.
[http://dx.doi.org/10.7150/jca.47902] [PMID: 32922554]
[68]
El-Mesery, M.; Seher, A.; El-Shafey, M.; El-Dosoky, M.; Badria, F.A. Repurposing of quinoline alkaloids identifies their ability to enhance doxorubicin-induced sub-G0/G1 phase cell cycle arrest and apoptosis in cervical and hepatocellular carcinoma cells. Biotechnol. Appl. Biochem., 2021, 68(4), 832-840.
[http://dx.doi.org/10.1002/bab.1999] [PMID: 32757395]
[69]
Liang, F.; Lv, Y.; Qiao, X.; Zhang, S.; Shen, S.; Wang, C.; Xu, G.; Zou, X.; Wang, L.; Zhang, B. Cinchonine-induced cell death in pancreatic cancer cells by downregulating RRP15. Cell Biol. Int., 2023, 47(5), 907-919.
[http://dx.doi.org/10.1002/cbin.11987] [PMID: 36682038]
[70]
González-Castejón, M.; Rodriguez-Casado, A. Dietary phytochemicals and their potential effects on obesity: A review. Pharmacol. Res., 2011, 64(5), 438-455.
[http://dx.doi.org/10.1016/j.phrs.2011.07.004] [PMID: 21798349]
[71]
Kumar, V.; Singh, D.D.; Lakhawat, S.S.; Yasmeen, N.; Pandey, A.; Singla, R.K. Biogenic phytochemicals modulating obesity: From molecular mechanism to preventive and therapeutic approaches. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-20.
[http://dx.doi.org/10.1155/2022/6852276] [PMID: 35388304]
[72]
Ordovas, J.M.; Shen, J. Gene-environment interactions and susceptibility to metabolic syndrome and other chronic diseases. J. Periodontol., 2008, 79(8S)(Suppl.), 1508-1513.
[http://dx.doi.org/10.1902/jop.2008.080232] [PMID: 18673004]
[73]
Marti, A.; Martinez-González, M.A.; Martinez, J.A. Interaction between genes and lifestyle factors on obesity. Proc. Nutr. Soc., 2008, 67(1), 1-8.
[http://dx.doi.org/10.1017/S002966510800596X] [PMID: 18234126]
[74]
Weisberg, S.P.; McCann, D.; Desai, M.; Rosenbaum, M.; Leibel, R.L.; Ferrante, A.W., Jr Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest., 2003, 112(12), 1796-1808.
[http://dx.doi.org/10.1172/JCI200319246] [PMID: 14679176]
[75]
Xu, H.; Barnes, G.T.; Yang, Q.; Tan, G.; Yang, D.; Chou, C.J.; Sole, J.; Nichols, A.; Ross, J.S.; Tartaglia, L.A.; Chen, H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest., 2003, 112(12), 1821-1830.
[http://dx.doi.org/10.1172/JCI200319451] [PMID: 14679177]
[76]
Ouchi, N.; Parker, J.L.; Lugus, J.J.; Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol., 2011, 11(2), 85-97.
[http://dx.doi.org/10.1038/nri2921] [PMID: 21252989]
[77]
Jo, J.; Gavrilova, O.; Pack, S.; Jou, W.; Mullen, S.; Sumner, A.E.; Cushman, S.W.; Periwal, V. Hypertrophy and/or hyperplasia: Dynamics of adipose tissue growth. PLOS Comput. Biol., 2009, 5(3), e1000324.
[http://dx.doi.org/10.1371/journal.pcbi.1000324] [PMID: 19325873]
[78]
Christodoulides, C.; Lagathu, C.; Sethi, J.K.; Vidal-Puig, A. Adipogenesis and WNT signalling. Trends Endocrinol. Metab., 2009, 20(1), 16-24.
[http://dx.doi.org/10.1016/j.tem.2008.09.002] [PMID: 19008118]
[79]
Jung, S.A.; Choi, M.; Kim, S.; Yu, R.; Park, T. Cinchonine prevents high-fat-diet-induced obesity through downregulation of adipogenesis and adipose inflammation. PPAR Res., 2012, 2012, 1-11.
[http://dx.doi.org/10.1155/2012/541204] [PMID: 22675336]
[80]
Dubey, A.; Singh, Y. Medicinal properties of cinchona alkaloids - a brief review. Asian J. Pharm. Sci., 2021, 11(3), 224-228.
[http://dx.doi.org/10.52711/2231-5659.2021.00036]
[81]
Xue, H.; Xing, H.J.; Wang, B.; Fu, C.; Zhang, Y.S.; Qiao, X.; Guo, C.; Zhang, X.L.; Hu, B.; Zhao, X.; Deng, L.J.; Zhu, X.C.; Zhang, Y.; Liu, Y.F. Cinchonine, a potential oral small-molecule glucagon-like peptide-1 receptor agonist, lowers blood glucose and ameliorates non-alcoholic steatohepatitis. Drug Des. Devel. Ther., 2023, 17, 1417-1432.
[http://dx.doi.org/10.2147/DDDT.S404055] [PMID: 37197367]
[82]
Sae-tan, S.; Grove, K.A.; Kennett, M.J.; Lambert, J.D. (−)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice. Food Funct., 2011, 2(2), 111-116.
[http://dx.doi.org/10.1039/c0fo00155d] [PMID: 21779555]
[83]
Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: Nuclear control of metabolism. Endocr. Rev., 1999, 20(5), 649-688.
[PMID: 10529898]
[84]
Ejaz, A.; Wu, D.; Kwan, P.; Meydani, M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J. Nutr., 2009, 139(5), 919-925.
[http://dx.doi.org/10.3945/jn.108.100966] [PMID: 19297423]
[85]
Pap, T.; Van Der Laan, W.H.; Aupperle, K.R.; Gay, R.E.; Verheijen, J.H.; Firestein, G.S.; Gay, S.; Neidhart, M. Modulation of fibroblast-mediated cartilage degradation by articular chondrocytes in rheumatoid arthritis. Arthritis Rheum., 2000, 43(11), 2531-2536.
[http://dx.doi.org/10.1002/1529-0131(200011)43:11<2531::AID-ANR21>3.0.CO;2-V] [PMID: 11083277]
[86]
Fox, R.I.; Kang, H.I. Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus, 1993, 2(S1), 9-12.
[http://dx.doi.org/10.1177/0961203393002001031] [PMID: 8097945]
[87]
Brass, L.F.; Hoxie, J.A.; Kieber-Emmons, T.; Manning, D.R.; Poncz, M.; Woolkalis, M. Agonist receptors and G proteins as mediators of platelet activation. In: Advances in Experimental Medicine and Biology; Springer US: Boston, MA, 1993; pp. 17-36.
[http://dx.doi.org/10.1007/978-1-4615-2994-1_2]
[88]
Brass, L.F.; Hoxie, J.A.; Manning, D.R. Signaling through G proteins and G protein-coupled receptors during platelet activation. Thromb. Haemost., 1993, 70(1), 217-223.
[http://dx.doi.org/10.1055/s-0038-1646194] [PMID: 8236108]
[89]
Saeed, S.A.; Gilani, A.H.; Majoo, R.U.; Shah, B.H. Anti-thrombotic and anti-inflammatory activities of protopine. Pharmacol. Res., 1997, 36(1), 1-7.
[http://dx.doi.org/10.1006/phrs.1997.0195] [PMID: 9368908]
[90]
Torti, M.; Lapetina, E.G. Structure and function of rap proteins in human platelets. Thromb. Haemost., 1994, 71(5), 533-543.
[http://dx.doi.org/10.1055/s-0038-1642478] [PMID: 8091376]
[91]
Heemskerk, J.W.M.; Sage, S.O. Calcium signalling in platelets and other cells. Platelets, 1994, 5(6), 295-316.
[http://dx.doi.org/10.3109/09537109409006439] [PMID: 21043702]
[92]
Shah, B.H.; Nawaz, Z.; Virani, S.S.; Ali, I.Q.; Saeed, S.A.; Gilani, A.H. The inhibitory effect of cinchonine on human platelet aggregation due to blockade of calcium influx. Biochem. Pharmacol., 1998, 56(8), 955-960.
[http://dx.doi.org/10.1016/S0006-2952(98)00094-X] [PMID: 9776305]
[93]
Singh, P.; Singh, I.; Mondal, S.; Singh, L.; Garg, V. Platelet-Activating Factor (PAF)-Antagonists of Natural Origin. Fitoterapia, 2012, 84, 180-201.
[PMID: 23160091]
[94]
Saeed, S.A.; Afzal, M.N.; Shah, B.H. Dual effects of nimesulide, a COX-2 inhibitor, in human platelets. Life Sci., 1998, 63(20), 1835-1841.
[http://dx.doi.org/10.1016/S0024-3205(98)00457-3] [PMID: 9820127]
[95]
Kim, J.M.; Lin, C.; Stavre, Z.; Greenblatt, M.B.; Shim, J.H. Osteoblast-osteoclast communication and bone homeostasis. Cells, 2020, 9(9), 2073.
[http://dx.doi.org/10.3390/cells9092073] [PMID: 32927921]
[96]
Zaidi, M. Skeletal remodeling in health and disease. Nat. Med., 2007, 13(7), 791-801.
[http://dx.doi.org/10.1038/nm1593] [PMID: 17618270]
[97]
D’Amico, L.; Roato, I. Cross-talk between T cells and osteoclasts in bone resorption. Bonekey Rep., 2012, 1(6), 82.
[http://dx.doi.org/10.1038/bonekey.2012.82] [PMID: 23951473]
[98]
Ono, T.; Nakashima, T. Recent advances in osteoclast biology. Histochem. Cell Biol., 2018, 149(4), 325-341.
[http://dx.doi.org/10.1007/s00418-018-1636-2] [PMID: 29392395]
[99]
Jianwei, W.; Ye, T.; Hongwei, W.; Dachuan, L.; Fei, Z.; Jianyuan, J.; Hongli, W. The role of TAK1 in RANKL-induced osteoclastogenesis. Calcif. Tissue Int., 2022, 111(1), 1-12.
[http://dx.doi.org/10.1007/s00223-022-00967-z] [PMID: 35286417]
[100]
Jo, Y.J.; Lee, H.I.; Kim, N.; Hwang, D.; Lee, J.; Lee, G.R.; Hong, S.E.; Lee, H.; Kwon, M.; Kim, N.Y.; Kim, H.J.; Park, J.H.; Kang, Y.H.; Kim, H.S.; Lee, S.Y.; Jeong, W. Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis. J. Cell. Physiol., 2021, 236(3), 1854-1865.
[http://dx.doi.org/10.1002/jcp.29968] [PMID: 32700766]
[101]
Leverrier, A.; Bero, J.; Frédérich, M.; Quetin-Leclercq, J.; Palermo, J. Antiparasitic hybrids of Cinchona alkaloids and bile acids. Eur. J. Med. Chem., 2013, 66, 355-363.
[http://dx.doi.org/10.1016/j.ejmech.2013.06.004] [PMID: 23816880]
[102]
Bawa, S.; Kumar, S.; Drabu, S.; Kumar, R. Structural modifications of quinoline-based antimalarial agents: Recent developments. J. Pharm. Bioallied Sci., 2010, 2(2), 64-71.
[http://dx.doi.org/10.4103/0975-7406.67002] [PMID: 21814435]
[103]
Abdelwahid, M.A.S.; Elsaman, T.; Mohamed, M.S.; Latif, S.A.; Mukhtar, M.M.; Mohamed, M.A. Synthesis, characterization, and antileishmanial activity of certain quinoline-4-carboxylic acids. J. Chem., 2019, 2019, 1-9.
[http://dx.doi.org/10.1155/2019/2859637]
[104]
Musikant, D.; Leverrier, A.; Bernal, D.; Ferri, G.; Palermo, J.A.; Edreira, M.M. Hybrids of Cinchona alkaloids and bile acids as antiparasitic agents against Trypanosoma cruzi. Molecules, 2019, 24(17), 3168.
[http://dx.doi.org/10.3390/molecules24173168] [PMID: 31480402]
[105]
Merschjohann, K.; Sporer, F.; Steverding, D.; Wink, M. in vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense. Planta Med., 2001, 67(7), 623-627.
[http://dx.doi.org/10.1055/s-2001-17351] [PMID: 11582539]
[106]
Rosenkranz, V.; Wink, M. Alkaloids induce programmed cell death in bloodstream forms of trypanosomes (Trypanosoma b. brucei). Molecules, 2008, 13(10), 2462-2473.
[http://dx.doi.org/10.3390/molecules13102462] [PMID: 18833031]
[107]
Desai, S.A. Why do malaria parasites increase host erythrocyte permeability? Trends Parasitol., 2014, 30(3), 151-159.
[http://dx.doi.org/10.1016/j.pt.2014.01.003] [PMID: 24507014]
[108]
Dunn, M.J. Alterations of red blood cell sodium transport during malarial infection. J. Clin. Invest., 1969, 48(4), 674-684.
[http://dx.doi.org/10.1172/JCI106025] [PMID: 4975361]
[109]
Bookchin, R.M.; Lew, V.L.; Nagel, R.L.; Raventos, C. Increase in potassium and calcium-transport in human red-cells infected with plasmodium-falciparum in vitro. Cambridge University press: New York, NY, 1981; pp. P65-P65.
[110]
Ginsburg, H.; Kutner, S.; Krugliak, M.; Ioav Cabantchik, Z. Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol. Biochem. Parasitol., 1985, 14(3), 313-322.
[http://dx.doi.org/10.1016/0166-6851(85)90059-3] [PMID: 3887158]
[111]
Ginsburg, H. How and why does the malarial parasite permeabilize its host cell membrane? In: Biomembranes; Benga, G.; Tager, J.M., Eds.; Springer Berlin Heidelberg: Berlin, Heidelberg, 1988; pp. 188-203.
[http://dx.doi.org/10.1007/978-3-642-61374-6_12]
[112]
Wiwanitkit, V. Antimalarial drug and renal toxicity. J. Nephropharmacol., 2015, 5(1), 11-12.
[PMID: 28197492]
[113]
Druilhe, P.; Brandicourt, O.; Chongsuphajaisiddhi, T.; Berthe, J. Activity of a combination of three cinchona bark alkaloids against Plasmodium falciparum in vitro. Antimicrob. Agents Chemother., 1988, 32(2), 250-254.
[http://dx.doi.org/10.1128/AAC.32.2.250] [PMID: 3284455]
[114]
Rasoanaivo, P.; Wright, C.W.; Willcox, M.L.; Gilbert, B. Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malar. J., 2011, 10(S1), S4.
[http://dx.doi.org/10.1186/1475-2875-10-S1-S4] [PMID: 21411015]
[115]
Kirk, K.; Wong, H.Y.; Elford, B.C.; Newbold, C.I.; Ellory, J.C. Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Biochem. J., 1991, 278(2), 521-525.
[http://dx.doi.org/10.1042/bj2780521] [PMID: 1898345]
[116]
Lamalle, C.; Marini, R.D.E.A.; Debrus, B.; Lebrun, P.; Crommen, J.; Hubert, P.; Servais, A.C.; Fillet, M. Development of a generic micellar electrokinetic chromatography method for the separation of 15 antimalarial drugs as a tool to detect medicine counterfeiting. Electrophoresis, 2012, 33(11), 1669-1678.
[http://dx.doi.org/10.1002/elps.201100621] [PMID: 22887081]
[117]
Morais, C.M.G.; Brito, R.M de M.; Weselucha-Birczyńska, A.; Pereira, V.S de S.; Pereira-Silva, J.W.; Menezes, A.; Pessoa, F.A.C.; Kucharska, M.; Birczyńska-Zych, M.; Ríos-Velásquez, C.M.; de Andrade-Neto, V.F. Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex. Front Cell Infect Microbiol., 2022, 12, 1047269.
[http://dx.doi.org/10.3389/fcimb.2022.1047269]
[118]
Skogman, ME; Kujala, J; Busygin, I; Leino, R; Vuorela, PM; Fallarero, A Evaluation of antibacterial and anti-biofilm activities of cinchona alkaloid derivatives against staphylococcus aureus. Nat Prod Commun., 2012, 7(9), 1934578X1200700917.
[http://dx.doi.org/10.1177/1934578X1200700917]
[119]
Ramić, A.; Skočibušić, M.; Odžak, R.; Čipak Gašparović, A.; Milković, L.; Mikelić, A.; Sović, K.; Primožič, I.; Hrenar, T. Antimicrobial Activity of Quasi-Enantiomeric Cinchona Alkaloid Derivatives and Prediction Model Developed by Machine Learning. Antibiotics (Basel), 2021, 10(6), 659.
[http://dx.doi.org/10.3390/antibiotics10060659] [PMID: 34073082]
[120]
Ren, J.; Zeng, W.; Jiang, C.; Li, C.; Zhang, C.; Cao, H.; Li, W.; He, Q. Inhibition of porcine epidemic diarrhea virus by cinchonine via inducing cellular autophagy. Front Cell Infect. Microbiol., 2022, 12, 856711.
[http://dx.doi.org/10.3389/fcimb.2022.856711]
[121]
Guo, X.; Zhang, M.; Zhang, X.; Tan, X.; Guo, H.; Zeng, W.; Yan, G.; Memon, A.; Li, Z.; Zhu, Y.; Zhang, B.; Ku, X.; Wu, M.; Fan, S.; He, Q. Porcine epidemic diarrhea virus induces autophagy to benefit its replication. Viruses, 2017, 9(3), 53.
[http://dx.doi.org/10.3390/v9030053] [PMID: 28335505]
[122]
Che, Z.P.; Yang, J.M.; Zhang, S.; Sun, D.; Tian, Y.E.; Liu, S.M.; Lin, X.M.; Jiang, J.; Chen, G.Q. Synthesis of novel 9 R/S -acyloxy derivatives of cinchonidine and cinchonine as insecticidal agents. J. Asian Nat. Prod. Res., 2021, 23(2), 163-175.
[http://dx.doi.org/10.1080/10286020.2020.1729136] [PMID: 32091234]
[123]
The insecticidal effect of the botanical insecticide chlorogenic acid on Mythimna separata (Walker) is related to changes in MsCYP450 gene expression. Front Plant Sci., 2022, 13, 1015095.
[124]
Rankovic, G.; Stankovic, V.; Zivkovic, M.; Rankovic, B.; Laketic, D.; Potic, M.; Saranovic, M.; Rankovic, G.N. Effects of cinchonine, a Cinchona bark alkaloid, on spontaneous and induced rat ileum contractions. Bratisl. Med. J., 2019, 120(8), 576-580.
[http://dx.doi.org/10.4149/BLL_2019_094] [PMID: 31379180]
[125]
Mulchinski, E.A.; Rao, S.S.; Agarwal, A.K. Comparative in vitro renal damage due to stereoisomeric cinchona alkaloids. Res. Commun. Chem. Pathol. Pharmacol., 1994, 83(1), 103-112.
[PMID: 8165364]
[126]
Leitzmann, C. Characteristics and Health Benefits of Phytochemicals. Forsch. Komplement. Med., 2016, 23(2), 69-74.
[PMID: 27160996]
[127]
Ruiz-Mesia, L.; Ruiz-Mesía, W.; Reina, M.; Martínez-Diaz, R.; de Inés, C.; Guadaño, A.; González-Coloma, A. Bioactive cinchona alkaloids from Remijia peruviana. J. Agric. Food Chem., 2005, 53(6), 1921-1926.
[http://dx.doi.org/10.1021/jf048880e] [PMID: 15769114]
[128]
Sano, R.; Reed, J.C. ER stress-induced cell death mechanisms. Biochim Biophys Acta BBA - Mol. Cell Res., 2013, 1833(12), 3460-3470.

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