Brassinosteroids: synthesis and biological activitiesby Jana Oklestkova, Lucie Rárová, Miroslav Kvasnica, Miroslav Strnad

Phytochem Rev

About

Year
2015
DOI
10.1007/s11101-015-9446-9
Subject
Biotechnology / Plant Science

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Brassinosteroids: synthesis and biological activities

Jana Oklestkova . Lucie Ra´rova´ .

Miroslav Kvasnica . Miroslav Strnad

Received: 29 September 2015 / Accepted: 27 October 2015  Springer Science+Business Media Dordrecht 2015

Abstract Brassinosteroids (BRs) are a relatively recently discovered group of phytohormones that are essential for normal plant growth and development.

They participate in regulation of numerous vital physiological processes in plants, such as elongation, germination, photomorphogenesis, immunity and reproductive organ development. Structurally they are very similar to animal steroid hormones and include about 70 polyhydroxylated sterol derivatives.

They are found at low levels in practically all plant organs. Recent studies have indicated that BRs have antiproliferative, anticancer, antiangiogenic, antiviral and antibacterial properties in animal cell systems, and thus have potential medical applications. Among others, BRs can inhibit replication of viruses in confluent human cell cultures, sometimes with high selectivity indexes, inducing cytotoxic effects in various types of cancer cells but not normal human cells. Thus, they include promising leads for developing potent new anticancer drugs. The aims of this article are to overview chemical characteristics, biological activities and the potential medical applications of natural BRs.

Keywords Brassinosteroids  Chemical synthesis 

Plant biological activity  Antiproliferative activity 

Antiviral activity

Introduction

Brassinosteroids (BRs) are a class of plant-specific steroid hormones characterized by polyhydroxylated sterol structures with significant growth-promoting activities (Clouse and Sasse 1998). They were initially reported at the start of the 1970s, when Mitchell et al. (1970, 1971) showed that ether extracts of Brassica napus (rape) pollen, designated ‘‘brassin’’, promote stem elongation and cell division in the bean internode assay. The first BR to be isolated, from 40 kg of beecollected rape pollen was named brassinolide (2) (Grove et al. 1979). All BRs have a 5a-cholestane skeleton, with functional variations due to differences in orientations of oxygenated functions on the skeleton (Bajguz and Tretyn 2003).

BRs are distributed throughout the plant kingdom and have been isolated, to date, from 64 plant species including 53 angiosperms, one pteridophyte, one bryophyte and three algae (Bajguz 2011). They have been detected in all examined plant organs, including pollen, seeds, leaves, stems, roots, flowers and grains.

They are also present in insect and crown galls.

However, pollen and seeds are the richest sources of

BRs, with contents in the 1–100 ng g-1 FW range, while shoots and leaves usually have much lower

J. Oklestkova (&)  L. Ra´rova´  M. Kvasnica  M. Strnad

Laboratory of Growth Regulators, Centre of the Region

Hana´ for Biotechnological and Agricultural Research,

Institute of Experimental Botany ASCR, Palacky´

University, Sˇlechtitelu˚ 27, 783 71 Olomouc,

Czech Republic e-mail: jana.oklestkova@upol.cz 123

Phytochem Rev

DOI 10.1007/s11101-015-9446-9 amounts, 0.01–0.1 ng g-1 FW (Bajguz 2011). BRs are involved in the regulation of many vital plant physiological activities, such as cell expansion, cell division, vegetative growth, reproduction, senescence, seed germination and stress tolerance (Clouse 2002;

Bhardwaj et al. 2006; Krishna 2003). Recent studies have shown that BRs also have potent antiviral, antifungal, antiproliferative, antibacterial, neuroprotective and antiangiogenic activities in animal and human systems (Wachsman et al. 2000, 2002; Michelini et al. 2004, 2008; Malı´kova´ et al. 2008; Steigerova´ et al. 2010; Ra´rova´ et al. 2012).

An array of brassinosteroids with variations in C-24 alkyl substituents are synthesized from campesterol, sitosterol, and cholesterol. All three sterols are converted to large numbers of metabolites in plant cells, but only a few of the metabolites have biological activity and biosynthetic pathways starting from campesterol seem to be the most important in planta (Hartmann 1998). Three major pathways of BR biosynthesis starting from this precursor are known.

In two of these pathways the intermediate campestanol is converted via either an ‘‘early’’ or ‘‘late’’ C-6 oxidation route, in which C-6 oxidation occurs before and after introduction of C22 and C23 vicinal hydroxyls, respectively (Fujioka and Yokota 2003).

These parallel pathways converge at castasterone (1), the immediate precursor of BL. Late C-6 oxidation is more prevalent in a number of species, including

Arabidopsis and pea (Nomura et al. 2001). The third pathway, proposed by Ohnishi et al. (2006) following analysis of BR biosynthesis in Arabidopsis, involves direct (campestanol-independent) conversion of early

C22-hydroxylated intermediates to 3-dehydro-6deoxoteasterone and 6-deoxotyhpasterol via C-23 hydroxylation. Proteins involved in BR signal transduction pathways have also been identified. In

Arabidopsis BRs are perceived by the BR INTENSIVE1 (BRI1) plasma-membrane receptor kinase and activation of BRI1/BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) kinase complexes by transphosphorylation. Subsequently, BRASSINOSTEROID INSENSITIVE 2 (BIN2) kinase is dephosphorylated and inactivated, resulting in the accumulation of unphosphorylated BRASSINAZOLE

RESISTANT (BZR) transcription factors in the nucleus (Kim and Wang 2010; Li and Chory 1997;

Wang et al. 2001). In this review we summarize current knowledge about BRs’ chemistry and biological activities in plant and animal systems (Fig. 1).

Chemistry

The first syntheses of BRs were described shortly after their isolation and structural determination, when

Thompson et al. (1979) published syntheses of 24-epicastasterone (24-epiCS, 3) and 24-epibrassinolide (24-epiBl, 4). Starting from commercially available ergosterol (7), these BRs were respectively obtained after nine and 12 steps, as shown in

Scheme 1. The most important reactions in this scheme are isomerization and formation of i-ergosterol (9), oxidation to i-sterone (10), reduction of the 7-double bond, formation of 2,3-olefin 14, cis-dihydroxylation, and Baeyer–Villiger oxidation. This is still a standard strategy for preparation of 24-epibrassinosteroids and few improvements have been published. However, McMorris and Patil (1993) improved synthesis of 24-epibrassinolide (4), reducing the number of reaction steps to seven. This was done by catalyzing isomerization of i-sterone (5) to 2,3olefin (14) using pyridinium hydrochloride and lithium bromide in one step, and performing the