Two New Cytotoxic C-29 Steroids from the Red Sea Brown Alga Cystoseira trinodis

Abstract

Chromatographic fractionation of the organic extract obtained from the brown alga Cystoseira trinodis led to the isolation of a known carotene pigment (7), five C-29 steroids (2-6), including two new ones (2 and 5), and an unexpected metabolite, halogenated cyclic ene-yne ether (1). Compound 1 was isolated from the genus Cystoseira for the first time. This finding plays an important role in the chemo-taxonomical differentiation of C. trinodis from other Cystoseira species. All compounds (1-7) were evaluated for their in vitro cytotoxic activities against four human tumor cell lines HepG2, WI 38, and Vero. They showed moderate cytotoxicity with IC 50 in the range 7-33 PM, where 7 exhibited the highest antioxidant activity with 72.1% inhibition.Marine macro-organisms, particularly algae, are considered as a platform of metabolites that possess a diversity of chemical structures as well as potent pharmacological activities [1]. Recently, the literature showed a wide range of biological activities of secondary metabolites isolated from algae, including anti-HIV, anticoagulant, anticonvulsant, anti-inflammatory, antineoplastic, and cytotoxic activities [2-4]. Generally, but not exclusively, diterpenes and sterols are isolated from brown algae [5] belonging to the genus Cystoseira [6][7][8]. For instances, four acetate cytotoxic hydroazulene diterpenes, dictyone acetate, dictyol F monoacetate, isodictytriol monoacetate, and cystoseirol monoacetate, were isolated from Cystoseira myrica [9]. A meroditerpenoid metabolite was isolated from the brown alga Cystoseira tamariscifolia [10].As a part of our systematic endeavors to isolate bioactive metabolites from Saudi Red Sea organisms, we investigated the constituents of C. trinodis (order: Fucales; family: Fucaceae) collected off the coast of Jeddah, KSA. We report here the isolation and characterization of two new metabolites, (24E)-stigmasta-5,24(28)-dien-3D-ol (2) and stigmasta-5,24(28)-dien-3E,29-diol (5), along with five known compounds: a halogenated cyclic ene-yne ether, (12E)-cis-maneonene-E (1) [11]; three steroids, stigmast-5-en-3E-ol (3) [12], 24-vinylcholesterol (4) [13], and fucosterol (6) [12]; and the allenic carotenoid fucoxanthin (7) [14].Compound 1 was identified as (12E)-cis-maneonene-E [11] and reported herein for the first time from C. trinodis (kingdom: Chromalveolata; phylum: Heterokontophyta; class: Phaeophyceae; order: Fucales; family: Fucaceae; genus: Cystoseira L). It represents a new trend in the isolation of unique natural compounds from marine brown algae of the order Fucales. Compound 1 was isolated from the red algae Laurencia papillosa and L. obtuse [15] which were collected from the same location as C. trinodis.Compound 2 was isolated as an amorphous solid material; it gave a molecular ion peak in the HR-EI-MS at 412.3693 corresponding to a molecular formula of C 29 H 48 O requiring six unsaturation sites. Its ESI-MS showed a molecular ion at m/z 412.

Metabolites with Antioxidant Activity from Marine Macroalgae

“…The most active compounds reported are the halogenated monoterpene (1E,3R,4S,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloro-methyl)-3-methyl-octa-1,5,7-triene (90), isolated from the red alga Plocamium sp., and the carotenoids fucoxanthin (118) and violaxanthin (122), isolated from various macroalgae, with IC 50 values of 50.0, 19.6, and 68.9 µM, respectively [128,159,163]. Alarif et al (2015) isolated a series of C-29 steroids (102-106), along with fucoxanthin (118), from the brown alga Cystoseira trinodis and all compounds were evaluated for their antioxidant activity [135]. Steroids 102-106 showed moderate antioxidant activity (20.4 to 27.5%) in the ABST assay, while compound 118 exhibited significant levels of activity (72.1%).…”

“…Alarif et al (2015) isolated a series of C-29 steroids ( 102 – 106 ), along with fucoxanthin ( 118 ), from the brown alga Cystoseira trinodis and all compounds were evaluated for their antioxidant activity [ 135 ]. Steroids 102 – 106 showed moderate antioxidant activity (20.4 to 27.5%) in the ABST assay, while compound 118 exhibited significant levels of activity (72.1%).…”

Toxicity in vitro and in Zebrafish Embryonic Development of Gold Nanoparticles Biosynthesized Using Cystoseira Macroalgae Extracts

“…14 Also, some steroids and pigments from the Cystoseira species display antitumoral activity. [15][16][17] Apart from their versatility, AuNPs show good biocompatibility. However, the modification of their surface can alter toxicity, biodistribution, and pharmacokinetics.…”