Equilibrio de calcona-flavanona en la mezcla isomérica: 2',3,4,4',6'-Pentahidroxicalcona y Eriodictyol de Stevia lucida

Pablo Chacon Morales, Carolina Santiago Dugarte, Juan Manuel Amaro

Resumen


A partir de las hojas y tallos de Stevia lucida Lagasca (Asteraceae), se aisló una mezcla isomérica chalcona-flavanona en equilibrio, compuesta de 2',3,4,4',6'-pentahidroxichalcona (8) (eriodictyol-chalcona) y eriodictyol (9), como un cristal isomorfo en una proporción (8/9) 5:3. La mezcla se caracterizó estructuralmente mediante méto-dos espectroscópicos, incluidos experimentos de RMN 1D y 2D. La presencia de chalconas en el género Stevia se reporta aquí por segunda vez.

Recibido: 29-09-2020 Aceptado: 28-12-2020

Palabras clave


Chalconas; flavanonas; Mezcla en equilibrio; 2',3,4,4',6' pentahidroxichalcona; Eriodictyol; Stevia

Texto completo:

PDF

Referencias


BH Havsteen. The biochemistry and medical significance of the flavonoids. Pharmacology & Therapeutics, 96, 67-202 (2002)

CR Ferraz, TT Carvalho, MF Manchope, NA Artero, FS Ras-quel-Oliveira, V Fattori, R Casagrande, WA Verri Jr. Therapeu-tic potential of flavonoids in pain and inflammation: Mechanisms of action, pre-clinical and clinical data, and pharmaceutical de-velopment. Molecules, 25, 762-797 (2020).

 Bisol, P Santos de Campos, M Lazzaron Lamers. Flavonoids as anticancer therapies: A systematic review of clinical trials. Phytother. Res., 34, 568-582 (2020).

SS Costa, JNSS Couceiro, ICV Silva, DC Malvar, MAS Couti-nho, LMM Camargo, MF Muzitano, FA Vanderlinde. Flavo-noids in the therapy and prophylaxis of flu: A patent review. Ex-pert Opin. Ther. Patents, 22, 1111-1121 (2012).

MM Jucá, FMS Cysne Filho, J Cunha de Almeida, D da Silva Mesquita, J Rodrigues de Moraes Barriga, KC Ferreira Dias, TM Barbosa, L Costa Vasconcelos, LK Almeida Moreira Leal, JE Ribeiro, SM Mendes Vasconcelos. Flavonoids: Biological activi-ties and therapeutic potential. Nat. Prod. Res., 34, 692-705 (2020).

AM González-Paramás, B Ayuda-Durán, S Martínez, S Gonzá-lez-Manzano, C Santos-Buelga.The mechanisms behind the bio-logical activity of flavonoids. Curr. Med. Chem., 26, 6976-6985 (2019).

S Kumar, AK Pandey Chemistry and biological activities of flavonoids: An overview. The Scientific World Journal, 13, ID 162750 (2013).

AK Verma, R Pratap. The biological potential of flavones. Nat. Prod. Rep., 27, 1571-1593 (2010).

RJ Nijveldt, E van Nood, DEC van Hoorn, PG Boelens, K van Norren, PAM van Leeuwen. Flavonoids: A review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 74, 418-425 (2001).

A Ahmad, M Kaleem, Z Ahmed, H Shafiq. Therapeutic potential of flavonoids and their mechanism of action against microbial and viral infections-A review. Food Res. Internat., 77, 221-235 (2015).

D Ravishankar, AK Rajora, F Greco, HMI Osborn. Flavonoids as prospective compounds for anti-cancer therapy. Intern. J. Biochem. Cell Biol., 45, 2821-2831 (2013).

KE Heim, AR Tagliaferro, DJ Bobilya. Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships. J. Nutrit. Biochem., 13, 572-584 (2002).

NK Sahu, SS Balbhadra, J Choudhary, DV Kohli. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem., 19, 209-225 (2012).

AM Katsori, D Hadjipavlou-Litina. Recent progress in therapeu-tic applications of chalcones. Expert Opin. Ther. Patents, 21, 1575-1596 (2011).

DI Batovska, IT Todorova. Trends in utilization of the pharma-cological potential of chalcones. Curr. Clin. Pharmacol., 5, 1-29 (2010).

G Brahmachari. Naturally occurring flavanones: An overview. Nat. Prod. Commun., 3, 1337-1354 (2008).

K Patel, GK Singh, DK Patel. A review on pharmacological and analytical aspects of naringenin. Chin. J. Integr. Med., 24, 551-560 (2018).

A Roohbakhsh, H Parhiz, F Soltani, R Rezaee, M Iranshahi. Neuropharmacological properties and pharmacokinetics of the citrus flavonoids hesperidin and hesperetin-A mini-review. Life Sciences, 113, 1-6 (2014).

G Forkmann, W Heller. Biosynthesis of flavonoids. In: Compre-hensive Natural Products Chemistry, Vol 1 Polyketides and Oth-er Secondary Metabolites Including Fatty Acids and Their De-rivatives. D Barton, K Nakanishi, O Meth-Cohn, U Sankawa (Eds), pp 713-748. Pergamon Press, London (1999).

K Yonekura-Sakakibara, Y Higashi, R Nakabayashi. The origin and evolution of plant flavonoid metabolism. Front. Plant Sci., 10, 943 (2019).

B Winkel-Shirley. Flavonoid biosynthesis, a colorful model for genetics, biochemistry, cell biology and biotechnology. Plant Physiol., 126, 485-493 (2001).

JL Ferrer, MB Austin, C Stewart Jr., JP Noel. Structure and function of enzymes involved in the biosynthesis of phenylpropanoids. Plant Physiol. Biochem., 46, 356-370 (2008).

H Grisebach, K Hahlbrock. Enzymology and regulation of fla-vonoid and lignin biosynthesis in plants and plant cell suspension cultures. In: Recent Advances in Phytochemistry, Vol. 8 Metabo-lism and Regulation of Secondary Plant Products. VC Runeckles, EE Conn (Eds), pp 21-52. Academic Press. New York (1974).

Y Wang, S Chen, O Yu. Metabolic engineering of flavonoids in plants and microorganisms. Appl. Microbiol. Biotechnol., 91, 949-956 (2011).

TTH Dao, HJM Linthorst, R Verpoorte. Chalcone synthase and its functions in plant resistance. Phytochem. Rev., 10, 397-412 (2011).

YC Yin, XD Zhang, ZQ Gao, T Hu, Y Liu. The research pro-gress of chalcone isomerase (CHI) in plants. Mol. Biotechnol., 61, 32-52 (2019).

O Hokche, PE Berry, O Huber. Nuevo Catálogo de la Flora Vascular de Venezuela. Fundación Instituto Botánico de Vene-zuela Dr. Tobías Lasser. Caracas, Venezuela (2008).

JM Amaro, M Hung. Estudio fitoquímico de la flora andina venezolana III. Flavonoides y esteroides de la Stevia lucida La-gasca. Rev. Fac. Farm. ULA, 25, 125-134 (1985).

P Chacón-Morales, JM Amaro-Luis, A Bahsas. Isolation and characterization of (+)-mellein, the first isocoumarin reported in Stevia genus. Av. Quím., 8, 145-151 (2013).

JM Amaro, M Hung. Estudio fitoquímico de la flora andina venezolana IV. Estructura del ácido labd-13(Z)-en-8-ol-15-oico, un componente de la Stevia lucida Lagasca. Acta Cient. Venez., 39, 21-24 (1988).

JM Amaro-Luis. An ent-kaurenolide from Stevia lucida. Phyto-chemistry, 32, 1611-1613 (1993).

JM Amaro, M Adrián, CM. Cerda, P Joseph-Nathan. Longipine-ne derivatives from Stevia lucida and S. triflora. Phytochemis-try, 27, 1409-1412 (1988).

PA Chacón-Morales, C Santiago Dugarte, JM Amaro-Luis. Helenin from Stevia lucida. The first report of this natural eudesmanolide mixture in Eupatorieae tribe. Nat. Prod. Res., 1-4 (2020) DOI: 10.1080/14786419.2020.1739677.

P Chacón-Morales, JM Amaro-Luis. Síntesis de un derivado diosfenólico a partir de la 7,9-dihidroxi-longipin-2-en-1-ona. Av. Quím., 10, 41-47 (2015).

PA Chacón-Morales, C Santiago-Dugarte, JM Amaro-Luis. Unexpected reduction-allylic oxidation of hemisynthetic diosphenols from longipinene derivatives. Phytochem. Lett., 39, 105-110 (2020).

PA Chacón-Morales, JM Amaro-Luis. Meridane and uladane, two unprecedented sesquiterpene skeletons obtained by Wagner-Meerwein rearrangements of longipinane derivatives. Tetrah. Lett., 57, 2713-2716 (2016).

DS Reddy, AG Kutateladze. Computational structure revision of a longipinane derivative meridane. Tetrah. Lett., 57, 4727-4729 (2016).

PA Chacón-Morales, JM Amaro-Luis, AG Kutateladze. Struc-ture determination and mechanism of formation of a seco-moreliane derivative supported by computational analysis. J. Nat. Prod., 80, 1210-1214 (2017).

M Salmón, A Ortega, G García de la Mora, E Angeles. A Diter-penic Acid from Stevia lucida. Phyrochemistry, 22, 1512-1513 (1983).

D Guerra-Ramírez, CM Cerda-García-Rojas, AM Puentes, P Joseph-Nathan. Longipinene diesters from Stevia lucida. Phyto-chemistry, 48, 151-154 (1998).

PA Chacón Morales, C Santiago Dugarte, JM Amaro Luis. 2’,3,4-trihydroxychalcone, phloretin and calomelanone from Ste-via lucida. The first chalcones reported in Stevia genus. Biochem. System. Ecol., 77, 57-60 (2018).

TJ Mabry, KR Markham, MB Thomas. The Systematic Identifi-cation of Flavonoids, pp 165-174; 227-230. Springer-Verlag. Berlin (1970).

A Shafaghat, F Salimi, N Alaniyan, Z Shoaei. Flavonoids and an ester derivative isolated from Galium verum L. World Appl. Sci. J., 11, 473-477 (2010).

S Asen, JR Plimmer. 4,6,4’-Trihydroxyaurone and other flavo-noids from Limonium. Phytochemistry, 11, 2601-2603 (1972).

L Quast, R Wiermann. Über das vorkommen verschieden substituierter chalkone während der mikrosporogenese bei Tulipa. Experientia, 29, 1165-1166 (1973).

AE Kambal, EC Bate-Smith. A genetic and biochemical study on pericarp pigments in a cross between two cultivars of grain sorghum, Sorghum bicolor. Heredity, 37, 413-416 (1976).

Y Iijima, K Suda, T Suzuki, K Aoki, D Shibata. Metabolite profiling of chalcones and flavanones in tomato fruit. J. Japan. Soc. Hort. Sci., 77, 94-102 (2008).

B Han, Z Xin, S Ma, W Liu, B Zhang, L Ran, L Yi, D Ren. Comprehensive characterization and identification of antioxi-dants in Folium Artemisiae argyi using high-resolution tandem mass spectrometry. J. Chromatogr. B, 1063, 84-92 (2017).

W Greenaway, S English, J May, FR Whatley. Analysis of phenolics of bud exudate of Populus sieboldii by GC-MS. Phytochemistry, 30, 3005-3008 (1991).

P Guerrero-Castillo, S Reyes, J Robles, MJ Simirgiotis, B Sepul-veda, R Fernandez-Burgos, C Areche. Biological activity and chemical characterization of Pouteria lucuma seeds: A possible use of an agricultural waste. Wast. Manag., 88, 319-327 (2019).

M Alberstein, M Eisenstein, H Abeliovich. Removing allosteric feedback inhibition of tomato 4-coumarate:CoA ligase by di-rected evolution. The Plant Journal, 69, 57-69 (2012).

AB Christensen, PL Gregersen, J Schröder, DB Collinge. A chalcone synthase with an unusual substrate preference is ex-pressed in barley leaves in response to UV light and pathogen at-tack. Plant Mol. Biol., 37, 849-857 (1998).

A Peters, HAW Schneider-Poetsch, H Schwarz, G Weissenböck. Biochemical and immunological characterization of chalcone synthase from rye leaves. J. Plant Physiol., 133, 178-182 (1988).

W Hinderer, HU Seitz. Chalcone synthase from cell suspension cultures of Daucus carota L. Arch. Biochem. Biophys., 240, 265-272, (1985).

C Gosch, H Halbwirth, B Schneider, D Hölscher, K Stich. Clon-ing and heterologous expression of glycosyltransferases from Malus x domestica and Pyrus communis, which convert phloretin to phloretin 20-O-glucoside (phloridzin). Plant Sci., 178, 299-306 (2010).

FA Tomás-Barberán, MN Clifford. Flavanones, chalcones and dihydrochalcones-Nature, occurrence and dietary burden. J. Sci. Food Agric., 80, 1073-1080. (2000).

SZ Dziedzic, BJF Hudson. Polyhydroxy chalcones and flavanones as antioxidants for edible oils. Food Chem., 12, 205-212 (1983).

J Nishida, J Kawabata. DPPH radical scavenging reaction of hydroxy- and methoxychalcones. Biosci. Biotechnol. Biochem., 70, 193-202 (2006).

AR Bilia, AR Sannella, FF Vincieri, L Messori, A Casini, C Gabbiani, C Severini, G Majori. Antiplasmodial effects of a few selected natural flavonoids and their modulation of artemisinin activity. Nat. Prod. Commun., 12, 1999-2002 (2008).

X Sui, YC Quan, Y Chang, RP Zhang, YF Xu, LP Guan. Syn-thesis and studies on antidepressant activity of 2’,4’,6’-trihydroxychalcone derivatives. Med. Chem. Res., 21, 1290-1296 (2012).

GTT Nguyen, G Erlenkamp, O Jäck, A Küberl, M Bott, F Fiorani, H Gohlke, G Groth. Chalcone-based selective inhibitors of a C4 plant key enzyme as novel potential herbicides. Sci. Rep., 6, 27333 (2016).

LP Sun, LX Gao, WP Ma, FJ Nan, J Li, HR Piao. Synthesis and biological evaluation of 2,4,6-trihydroxychalcone derivatives as novel protein tyrosine phosphatase 1B inhibitors. Chem. Biol. Drug. Des., 80, 584-590 (2012).

JC Le Bail, C Pouget, C Fagnere, JP Basly, AJ Chulia, G Habrioux. Chalcones are potent inhibitors of aromatase and 17-hydroxysteroid dehydrogenase activities. Life Sci., 68, 751-761 (2001).

S Sogawa, Y Nihro, H Ueda, A Izumi, T Miki, H Matsumoto, T Satoh. 3,4-Dihydroxychalcones as potent 5-lipoxygenase and cy-clooxygenase inhibitors. J. Med. Chem., 36, 3904-3909 (1993).

FB Power, Tutin F. Chemical Examination of Eriodictyon. Proc. Am. Pharm. Assoc., 54, 352-369 (1906); Pharmac. Rev., 24, 300-304 (1907).

J Shinoda, I Sato. New synthesis of polyoxy-chalcone, -hydrochalcone and -flavanone, Part 4: On the structure of eriodictyol and homoeriodictyol in the synthetic rod of 3', 4'-dimetoxy-5, 7-bioxyflavanone. Yakugaku Zasshi, 49, 64-70 (1929).

J Shinoda, I Sato. New synthesis of polyoxy-chalcone, -hydrochalcone and -flavanone, Part 5: Synthesis of eryodictyol and homoeryodictyol. Yakugaku Zasshi, 49, 71-78 (1929).

A Islam, S Islam, K Rahman, N Uddin, R Akanda. The pharma-cological and biological roles of eriodictyol. Arch. Pharm. Res., 43, 582-592 (2020).

D Barreca, G Gattuso, E Bellocco, A Calderaro, D Trombetta, A Smeriglio, G Laganá, M Daglia, S Meneghini, SM Nabavi. Flavanones: Citrus phytochemical with health-promoting proper-ties. BioFactors, 43, 495-506 (2017).

S Belli, M Rossi, N Molasky, L Middleton, C Caldwell, C Bartow-McKenney, M Duong, J Chiu, E Gibbs, A Caldwell, C Gahn, F Caruso. Effective and novel application of hydrodynam-ic voltammetry to the study of superoxide radical scavenging by natural phenolic antioxidants. Antioxidants, 8, 14 (2019).

X Wang, R Deng, J Dong, L Huang, J Li, B Zhang. Eriodictyol ameliorates lipopolysaccharide-induced acute lung injury by suppressing the inflammatory COX-2/NLRP3/NF-κB pathway in mice. J. Biochem. Mol. Toxicol., 34, e22434 (2020).

P. Rajesh, V Manju. Eriodictyol imparting cardioprotection and lipid modulation in isoproterenol-induced myocardial infarcted rats. Res. J. Chem. Environ., 24, 112-119 (2020).

W Li, Q Du, X Li, X Zheng, F Lv, X Xi, G Huang, J Yang, S Liu. Eriodictyol inhibits proliferation, metastasis and induces apoptosis of glioma cells via PI3K/Akt/NF-kB signaling path-way. Front. Pharmacol., 11, 114 (2020).

L Yu, X Liu. Eriodictyol suppresses survival of cervical cancer cells through mediation of PTEN/Akt signaling pathway. Curr. Top. Nutra. Res., 18, 196-200 (2020).

JL Liu, YC Kong, JY Miao, XY Mei, SY Wub, YC Yan, XY Cao. Spectroscopy and molecular docking analysis reveal struc-tural specificity of flavonoids in the inhibition of α-glucosidase activity. Int. J. Biol. Macromol., 152, 981-989 (2020).

M Smith, JC Smith. Repurposing therapeutics for COVID-19: Supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface. ChemRxivTM, DOI:10.26434/chemrxiv.11871402.v4 (2020). [this article is a preprint; it may not have been peer reviewed].

RR Deshpande, AP Tiwari, N Nyayanit, M Modak. In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2. Eur. J. Pharmacol., 886, 173430 (2020).

R Spribille, G. Forkmann. Chalcone synthesis and hydroxylation of flavonoids in 3’-position with enzyme preparation from flow-ers of Dianthus caryophyllus L. (carnation). Planta, 155, 176-182 (1982).

R Sütfeld, R Wiermann. The Formation of flavanones from hydroxycinnamoyl-coenzyme A thiol esters and malonyl-coenzyme A by enzyme extracts from anthers. Z. Pflanzenphysiol., 79, 467-472 (1976).

C Dittmer, G Raabe, L Hintermann. Asymmetric cyclization of 2-hydroxychalcones to flavanones: Catalysis by chiral Brønsted acids and bases. Eur. J. Org. Chem., 5886-5898 (2007) and ref-erence here cited.

P Kulkarni, P Wagh, P Zubaidha. An improved and eco-friendly method for the synthesis of flavanone by the cyclization of 2’-hydroxy chalcone using methane sulphonic acid as catalyst. Chem. J., 2, 106-110 (2012) and reference here cited.

DG Bhosale, PS Kulkarni. Ferric sulphate solid acid catalyst for cyclization of 2’-hydroxychalcone to flavanone under micro-wave condition. Iran. J. Org. Chem., 5, 1061-1064 (2013) and reference here cited.

J Mai, E Hoxha, CE. Morton, BM Muller, MJ Adler. Towards a dynamic covalent molecular switch: Substituent effects in chalcone/flavanone isomerism. Org. Biomol. Chem., 11, 3421-3423 (2013).

BM Muller, TJ Litberg, RA Yocum, CA Pniewski, MJ Adler. Extended aromatic and heteroaromatic ring systems in the chalcone-flavanone molecular switch scaffold. J. Org. Chem., 81, 5775-5781 (2016).

S Moussouni, A Detsi, M Majdalani, DP Makris, P Kefalas. Crude peroxidase from onion solid waste as a tool for organic synthesis. Part I: Cyclization of 2’,3,4,4’,6’-pentahydroxy-chalcone into aureusidin. Tetrahedron Lett., 51, 4076-4078 (2010).




Depósito Legal: PPI200602ME2232
ISSN: 1856-5301

Creative Commons License
Todos los documentos publicados en esta revista se distribuyen bajo una
Licencia Creative Commons Atribución -No Comercial- Compartir Igual 4.0 Internacional.
Por lo que el envío, procesamiento y publicación de artículos en la revista es totalmente gratuito.