Lignans from Bursera Fagaroides: Chemistry, Pharmacological Effects and Molecular Mechanism

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Lignans from Bursera Fagaroides: Chemistry, Pharmacological Effects and Molecular Mechanism life Review Lignans from Bursera fagaroides: Chemistry, Pharmacological Effects and Molecular Mechanism. A Current Review Mayra Antúnez-Mojica 1 , Antonio Romero-Estrada 2, Israel Hurtado-Díaz 2 , Alfonso Miranda-Molina 3 and Laura Alvarez 4,* 1 CONACYT-Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico; [email protected] 2 Departamento de Madera, Celulosa y Papel, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Km 15.5 Carretera Guadalajara-Nogales, Col. Las Agujas, Zapopan 45100, Jalisco, Mexico; [email protected] (A.R.-E.); [email protected] (I.H.-D.) 3 LANEM-Centro de Investigaciones Químicas IICBA, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Cuernavaca 62209, Morelos, Mexico; [email protected] 4 Centro de Investigaciones Químicas IICBA, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Cuernavaca 62209, Morelos, Mexico * Correspondence: [email protected] Abstract: Bursera fagaroides is a medicinal tree endemic to México, it belongs to the Burseraceae family and has proven antitumor activity. Modern research, performed principally with the bark extracts, have indicated that lignans are the main active constituents of B. fagaroides, with a high content of Citation: Antúnez-Mojica, M.; aryltetralin, aryldihydronaphtalene, dibenzylbutirolactone, and dibenzylbutane-type lignans as the Romero-Estrada, A.; Hurtado-Díaz, I.; constituents of the active extracts. In general, lignans from B. fagaroides exhibited potent anti-cancer ac- Miranda-Molina, A.; Alvarez, L. tivity, although antitumor, anti-bacterial, anti-protozoal, anti-inflammatory, and anti-viral properties Lignans from Bursera fagaroides: have also been described. This review covers literature-reported lignans from B. fagaroides, chemical Chemistry, Pharmacological Effects structures, nomenclature, chromatographic techniques of isolation, characterization strategies, and and Molecular Mechanism. A highlights the anti-cancer molecular mechanisms of lignans. Evaluation of the anticancer function of Current Review. Life 2021, 11, 685. https://doi.org/10.3390/life11070685 lignans has been extensively investigated since the cytotoxic in vitro results and in vivo assays in mice and zebrafish models to the tubulin molecular recognition by NMR. Also, we discuss the future Academic Editors: Raffaele Capasso, direction for studying this important plant species and its lignan metabolites. Md. Moshfekus Saleh-E-In and Md. Adnan Keywords: Bursera fagaroides; lignans; tubulin; cytotoxicity Received: 29 June 2021 Accepted: 10 July 2021 Published: 13 July 2021 1. Introduction Cancer is well known as one of the most important causes of morbidity and mortality Publisher’s Note: MDPI stays neutral worldwide, its effects in both more and less economically developed countries, and its with regard to jurisdictional claims in likelihood to rank as the leading cause of death in the 21st century. It is estimated that published maps and institutional affil- this public health problem caused 9.6 million deaths worldwide in 2018 [1,2]. Currently, iations. there are various types of therapies for cancer treatment, but chemotherapy is one of the most widely used. However, because of the severe side effects exhibited by commercially available drugs to treat cancer, as well as the drug resistance in tumor cells, it remains a challenge for medicinal chemistry to develop novel agents and treatment strategies to Copyright: © 2021 by the authors. attack this public health problem [3,4]. According to the Food and Drug Administration Licensee MDPI, Basel, Switzerland. (FDA), 246 anti-cancer drugs were approved between 1940 and 2014 and around 38% of This article is an open access article them are natural products (or derived from them) [5]. In this context, one of the most distributed under the terms and important sources of anti-cancer secondary metabolites is the Bursera genus because it conditions of the Creative Commons has been reported that these plants are effective against different types of cancer [6]. The Attribution (CC BY) license (https:// genus Bursera Jacq. ex L. (Burseraceae) consists of about 105 shrubs and trees with a creativecommons.org/licenses/by/ geographical distribution extending from the Southern U.S. to Peru and the Caribbean. 4.0/). Life 2021, 11, 685. https://doi.org/10.3390/life11070685 https://www.mdpi.com/journal/life Life 2021, 11, x FOR PEER REVIEW 2 of 14 Life 2021, 11, 685 2 of 13 Bursera species grow principally in the tropical dry forests, where about 92 species have been described and most of them (~85%) are endemic [7,8]. Bursera has been divided into twoIn Mexico, subgenera the (subg.),Bursera speciesor sections: grow B. principally subg. Bursera in the and tropical B. subg. dry Elaphrium forests, where (previously about known92 species as Bullockia have been) [8]; described the bark, and among most of other them traits, (~85%) mainly are endemic differentiates [7,8]. Bursera betweenhas beenthem. Thedivided species into of two section subgenera Bursera (subg.), have colorful or sections: trunksB. andsubg. peelingBursera bark,and whileB. subg. speciesElaphrium of Ela- phrium(previously have knownrough and as Bullockia non-peeling)[8]; thebark bark, [9]. Several among otherBursera traits, species mainly are recognized differentiates be- causebetween of their them. characteristic The species production of section ofBursera an aromatichave colorful resin (exuded) trunks and known peeling as “copal” bark, thatwhile provides species a of chemicalElaphrium defensehave rough against and specialized non-peeling herbivores bark [9]. [10]. Several SinceBursera ancientspecies times, copalare recognized resin has been because commonly of their characteristicused in México production and Central of an America aromatic as resinincense (exuded) in reli- giousknown activities as “copal” [11,12]. that The provides chemical a chemical profile defenseof the species against of specializedBursera includes herbivores flavonoids [10]. [13,14],Since ancient triterpenes times, [15,16], copal resin sesquiterpenes has been commonly [16,17], usedditerpenes in México [18], and and Central lignans America [19,20]. as incense in religious activities [11,12]. The chemical profile of the species of Bursera Most of the Bursera species that produce lignans are widely used in México as traditional, includes flavonoids [13,14], triterpenes [15,16], sesquiterpenes [16,17], diterpenes [18], natural medicine due to their pharmacological properties, including analgesic, anti-in- and lignans [19,20]. Most of the Bursera species that produce lignans are widely used in flammatory, and antitumoral properties. Also, they can help treat different illnesses, such México as traditional, natural medicine due to their pharmacological properties, including as colds, polyps, and venereal diseases [6,21]. In general, lignans from the Bursera genus analgesic, anti-inflammatory, and antitumoral properties. Also, they can help treat different areillnesses, secondary such metabolites, as colds, polyps, known and for venereal their diseasesantioxidant, [6,21 apoptotic,]. In general, anti lignans-cancer, from anti the-in- flammatory,Bursera genus anti are-bacterial, secondary anti metabolites,-viral, anti known-fungal, for and their a antioxidant,nti-protozoal apoptotic, properties. anti-cancer, In partic- ular,anti-inflammatory, lignans from B. anti-bacterial, fagaroides have anti-viral, been reported anti-fungal, to have and an anti-protozoal important anti properties.-cancer effect In [6].particular, This review lignans aims from to B.summarize fagaroides haveliterature been findings reported on to havethe Mexican an important B. fagaroides anti-cancer, such aseffect uses [ 6in]. Thismedicinal review folk, aims pharmacologi to summarizecal literature effects of findings its extracts on the and Mexican chemistry,B. fagaroides and the, biologicalsuch as uses activities in medicinal of its lignans. folk, pharmacological This review focuses effects ofon its the extracts biosynthesis, and chemistry, chemical and as- pects,the biological anti-cancer activities effects, of and its lignans.molecular This mechanisms review focuses of lignans on the from biosynthesis, B. fagaroides. chemical The in- formationaspects, anti-cancer reported in effects, this andwork molecular results from mechanisms a search of in lignans ScienceDirect, from B. fagaroides. PubMed,The and Scifinderinformation databases. reported in this work results from a search in ScienceDirect, PubMed, and Scifinder databases. 2. Bursera fagaroides: Description, Distribution, and Uses in the Mexican Traditional Medicine2. Bursera fagaroides: Description, Distribution, and Uses in the Mexican Traditional Medicine Bursera fagaroides (B. subg. Bursera) (Figure 1), also identified as Elaphrium fagaroides, Bursera fagaroides (B. subg. Bursera) (Figure1), also identified as Elaphrium fagaroides, AmyrisAmyris fagaroides fagaroides, ,and and TerebinthusTerebinthus fagaroidesfagaroides,, isis aa MexicanMexican medicinal medicinal plant plant locally locally known known asas “copalillo”, “copalillo”, “aceitillo”, “aceitillo”, “copal”, “sarzafr“sarzafrás”ás” “xixote”,“xixote”, “cuajiote“cuajiote amarillo” amarillo” “jiote”, “jiote”, “palo “palo deldel diablo”, diablo”, “papelillo”, “papelillo”, and and “xicote” [[17,2217,22––2424].]. It isis anan aromaticaromatic bush bush or or tree tree of of about about 0.50.5–8–8 m m high, high, distributed
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