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Antifungal–antiproliferative norcycloartane-type triterpenes from the Red Sea green alga Tydemania expeditionis

  • Hajer S. Alorfi EMAIL logo
Published/Copyright: September 13, 2022
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Open Chemistry
From the journal Open Chemistry Volume 20 Issue 1

Abstract

The current work aims to isolate the bioactive secondary metabolites from the Red Sea green alga T. expeditionis. Its organic extract was partitioned and analyzed using chromatographic and spectroscopic techniques. Four triterpenoids of the cycloartane-carbon skeleton were identified as: 29-norcycloartane-3-en-23,28-diol (1), 29-norcycloartane-5,24-dien-3-ol-23-one (2), 29-norcycloartane-3,24-dien-3-ol-23-one (3), and 29-norcycloartane-5,24-dien-3-ol (4), along with hydroxylated C-18 fatty acid, 3-hydroxyoctadeca-15(Z)-enoic acid (5). The antiproliferative activity of the isolated metabolites was examined against three cancer cell lines, i.e., HeLa, HepG-2, and MCF-7. Compounds 2 and 3 demonstrated a strong antiproliferative effect against all cells with IC50 values ranging from 17.8 ± 1.71 to 23.3 ± 1.66 µM. Compounds 1 and 4 showed a moderate antiproliferative effect against all cell lines with IC50 values ranging from 44.7 ± 2.32 to 65.0 ± 3.66 µM. The antifungal activity of all compounds has been tested against several fungi. Compounds 2–4 revealed strong inhibition against A. flavus and Fusarium oxysporum. Compounds 1–4 showed moderate to weak inhibition activity against A. niger, A. fumigatus, C. albicans, and C. tropicalis. Compound 5 showed weak to non-detected activity against all cell lines and microbes. The results indicated that norcycloartanes exhibit antiproliferative and antifungal activities, especially those with α,β-unsaturated ketones in their side chain.

Keywords: seaweeds; chromatographic isolation; spectroscopy; antiproliferation; antifungal

1 Introduction

In the last decade, marine natural product specialists have greatly enhanced the search for new pharmaceutical armamentariums to reserve a distinguished position among today’s drugs. Marine algae continue to act as suppliers of astonishing natural organic substances that possess potential therapeutic effects [1,2]. Based on recently reported surveys, more than 72,000 species of macro-algae worldwide have been identified. The marine macro-algae, including Chlorophyta (green algae), Phaeophyta (brown algae), and Rhodophyta (red alga), constitute the most significant proportion of the total macro-algae on the earth [3].

As a matter of fact, marine algae are affected by harsh environmental circumstances, including but not limited to temperature, salinity, sunlight, and physiological conditions [4]. Despite various environmental conditions, marine algae can survive and grow through different adaptation strategies. This adaptive nature of marine macro-algae has enabled them to produce exclusive chemical skeletons such as polyketides, polysaccharides, tannins, steroids, terpenoids, shikimates, and alkaloids [3,5]. Chlorophytin seaweeds or marine green algae are common in intertidal and deep waters. Tydemania expeditionis (Udoteaceae) is a feeble calcium carbonate forming green alga, spread among tropical Indian and Pacific waters [6].

Phytochemical exploration of Tydemania expeditionis collected from Guam, the US territory, yielded three norcycloartene triterpenoids [7] and a linear diterpenoid [8]. A specimen of the same algal species collected from Micronesia was investigated and was found to contain cycloartanol sulfates [9]. Four cycloartenol sulfates and three β-hydroxyl unsaturated fatty acids were isolated from a sample of T. expeditionis collected in Fiji [10]. A study conducted by Zhang et al. [11] on a specimen collected in the China Sea revealed the isolation of several steroids, including a new diketosteroid, (E)-stigmasta-24(28)-en-3,6-dione [11]. The isolated new ketosteroid displayed remarkable affinity to the androgen receptor and unexpected weak activity to prostate cancer [11]. Sulfated cycloartenols exhibited antifungal activities [6] and inhibited the pp60v-src protein tyrosine kinase [9]. Antineoplastic fatty acid derivatives were also identified amongst the constituents of the Fijian green alga T. expeditionis; of these derivatives, polyunsaturated fatty acids (PUFA) of C16 and C18 carbon skeleton along with sphingolipids were isolated [12]. In line with a continued project aiming at the isolation of bioactive agents from the Red Sea macro-algae [13,14,15], a specimen of T. expeditionis collected in the Red Sea of Jeddah coast was phytochemically investigated for the isolation of new chemicals and/or identification of new biological effects of previously isolated compounds.

2 Experimental method

2.1 General

The column chromatography utilized silica gel of 60 mesh size (Fluka). The Thin-layer chromatography (TLC) was silica gel 60 mesh F 254 (Merck). The Preparative thin-layer chromatography (PTLC) was pre-coated glass plates (MACHEREY_NAGEL) G-25 UV254. The visualization employed a spray reagent (50% sulfuric acid in ethanol and p-anisaldehyde) and UV light. The chemicals used were crystal violet stain (1%); dimethyl sulfoxide (DMSO); MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye from Sigma (St. Louis, MO, USA); fetal bovine serum, DMEM, RPMI 1640, HEPES buffer solution, l-glutamine, gentamycin, and 0.25% Trypsin-EDTA from Lonza.

2.2 Extraction of the green alga Tydemania expeditionis

A specimen of T. expeditionis (Figure 1) was collected in June 2021 from the Jeddah coast (20°42′52.36″N; 39°29′20.74″E), Jeddah, Saudi Arabia. The air-dried sample (181.0 g) was macerated with an organic solvent mixture (n-hexane:diethylether:methanol [1:1:1, v/v/v]). A dark green residue (7.7 g) was obtained after complete solvent evaporation of the total extract. The whole algal extract was mixed with a suitable amount of silica gel (60 G) and poured into an open silica gel column. The elution process was started with n-hexane and the polarity was gradually elevated by adding diethyl ether, ethyl acetate, and methanol.

Figure 1 Molecular structures of compounds 1–5 isolated from Tydemania expeditionis.
Figure 1

Molecular structures of compounds 1–5 isolated from Tydemania expeditionis.

2.3 Isolation of compounds 1–5

Fraction A eluted with n-hexane:diethyl ether (90:10, v/v) was purified using PTLC and solvent system 15% diethyl ether in n-hexane. A dark red band with R f = 0.57 visualized upon spraying with p-anisaldehyde was scraped, and the silica was filtered to yield 1.9 mg of gummy residue (compound 3). Fraction B eluted with n-hexane:diethyl ether (75:25, v/v) was purified using PTLC and solvent system 30% diethyl ether in n-hexane. Three bands were developed in different R f values. The first was a purple band with R f = 0.86 (visualization after spraying p-anisaldehyde reagent to afford a pure oily material, 2.4 mg), yielding compound 5. The second was a crimson-red band with R f = 0.34 (visualization p-anisaldehyde reagent to afford a brown residue, 2.0 mg), yielding compound 4. The third was a crimson-red band with R f = 0.22 (visualization with a UV lamp and p-anisaldehyde reagent to afford a brown residue, 2.0 mg), yielding compound 2. Fraction C eluted with n-hexane:diethyl ether (60:40, v/v) was purified using PTLC and solvent system with 25% ethyl acetate in n-hexane. A dark red band with R f = 0.37 visualized upon spraying with p-anisaldehyde was scraped, and the silica was filtered to yield 1.6 mg of gummy residue (compound 1).

2.4 Characterization of the isolated compounds

2.4.1 29-Norcycloartane-3-en-23,28-diol (1)

Gummy residue; [α]D 22 + 12.3 (CHCl3, 0.02); IR ν max 3,470, 3,398, 2,921, 1,661, and 1,376 cm−1; HR-ESI-MS m/z 429.3740 [M + 1]+ (Calcd for C29H49O2, 429.3733); 1H and 13C NMR (CHCl3) (Table 1).

Table 1

1H and 13C NMR (400 and 100 MHz, respectively) spectral data of compound 1 in CDCl3 a

C No. b δ C δ H (J in Hz) c C No. δ C δ H (J in Hz)
1 34.3 (CH2) 1.71, m 16 26.2 (CH2) 1.90, m
1.46, m 1.25, m
2 23.6 (CH2) 2.11, m 17 52.7 (CH) 1.58, m
1.89, m
3 121.8 (CH) 5.37, brs 18 18.3 (CH3) 0.97, s
4 138.1 (C) — 19 22.2 (CH2) 0.48, d (4.4)
−0.7, d (4.4)
5 40.6 (CH) 2.28, m 20 32.8 (CH) 1.41, m
6 25.5 (CH2) 1.50, m 21 18.5 (CH3) 0.91, d (6.8)
1.23, m
7 27.8 (CH2) 1.65, m 22 44.9 (CH2) 1.49, m
1.35, m 0.94, m
8 43.0 (CH) 1.96, m 23 67.1 (CH) 3.77, m
9 21.7 (C) — 24 48.1 (CH2) 1.34, m
1.12, m
10 29.5 (C) — 25 24.8 (CH) 1.30, m
11 31.9 (CH2) 1.68, m 26 22.4 (CH3) 0.88, d (6.8)
1.42, m
12 34.1 (CH2) 1.30, m 27 23.2 (CH3) 0.88, d (6.8)
1.22, m
13 45.5 (C) — 28 62.2 (CH2) 4.29, dd (11.6, 4.0)
4.14, dd (11.6, 6.6)
14 49.5 (C) —
15 32.2 (CH2) 1.49, m
1.26, m

aAll assignments are based on 1D and 2D measurements (HMBC, HSQC, COSY). bImplied multiplicities were determined by DEPT (C = s, CH = d, CH2 = t). c J in Hz.

2.4.2 3-Hydroxyoctadeca-15(Z)-enoic acid (5)

Colorless oil; [α]D 22 + 8.1 (CHCl3, 0.01); IR ν max 3,434, 2,961, 1,715, and 1,665 cm−1; HR-ESI-MS m/z 297.2425 [M–H]+ (Calcd for C18H34O3, 297.2430); 1H and 13C NMR (CHCl3) (Table 2).

Table 2

1H and13C NMR spectral data of compound 5 in CDCl3

C no. δ C δ H (J in Hz)
1 178.3 —
2 35.3 2.30, m
2.25, m
3 70.6 4.10, m
4 34.5 1.40, m
5 29.7 1.25, m
6 29.7 1.27, m
7 29.7 1.27, m
8 29.7 1.27, m
9 29.7 1.27, m
10 29.7 1.27, m
11 29.7 1.27, m
12 29.7 1.27, m
13 29.7 1.28, m
14 27.6 2.10, m
15 124.3 5.10, m
16 133.5 5.34, m
17 20.7 2.04, m
18 13.6 0.93, t (6.8)

2.5 Biological activities

2.5.1 Cytotoxic assay

HeLa (human cervix adenocarcinoma), HepG-2 (human hepatocellular carcinoma), and MCF-7 (human breast carcinoma) cells were obtained from American Type Culture Collection (ATCC) and cultured in RPMI 1640 medium, Gibco, USA. The cytotoxicity assay was performed according to Mosmann [16].

2.5.2 Antifungal assay

The agar well diffusion method was used to determine the sensitivity of the pathogenic fungi to the isolated compounds (1–5) [17]. Over the surface of Mueller–Hinton agar, 0.5 mL of the bacterial suspension (4 × 106 CFU/mL) was spread, and agar wells (6 mm diameter) were filled with 50 µL of the tested material (10 µg/mL DMSO). On the surface of Sabouraud agar or potato dextrose agar, yeast cells or fungal spore suspensions containing 4 × 104 CFU/mL were spread. After an hour of incubation at room temperature, the inoculated plates were incubated for 24 h at 37°C for bacteria and 25°C for 4 days for fungi. Inhibition zone diameters were measured and the mean diameter of six replicates (mean value ± SD) was calculated. Amphotericin B was used as a positive control and DMSO was used as a negative control.

3 Results and discussion

Sequential chromatographic fractionation of the methylene chloride/methanol extract of the Red Sea green alga T. expeditionis yielded a total of five metabolites (1–5). Four of these metabolites belong to the cycloartane-type sesquiterpenoids, including compound 1: 29-norcycloartane-5,24-dien-3-ol-23-one (fraction C, a dark red band, R f = 0.37); compound 2: 29-norcycloartane-3,24-dien-3-ol-23-one (fraction B, a crimson-red band, R f = 0.22); compound 3: 29-norcycloartane-5-en-3,28-diol (fraction A, a dark red band, R f = 0.57); and compound 4: 29-norcycloartane-5,24-dien-3-ol (fraction B, a crimson-red band, R f = 0.34). Compound 5 belongs to the fatty acids, 3-hydroxyoctadeca-15(Z)-enoic acid (fraction B, a purple band, R f = 0.86). The identity of the isolated metabolites has been elucidated using different spectroscopic analyses in addition to mass spectrometry and comparison of the obtained data with those in the literature (Figure 2; Tables 1 and 2).

Figure 2 Selected 1H–1H COSY (▬) and HMBC () correlations of compounds 1 and 5.
Figure 2

Selected 1H–1H COSY (▬) and HMBC () correlations of compounds 1 and 5.

3.1 Structure elucidation

Compound 1 was isolated as a brown residue. Mass spectrometry showed a molecular ion [M + 1]+ at m/z 429.3733, assigned to a molecular formula of C29H48O2, with six sites of unsaturation. The IR spectrum (cm−1) showed bands due to hydroxyl function (3,470 and 3,398), carbon-carbon double bond (1,661), and gem-dimethyl (1,376). 13C NMR spectrum confirmed the presence of 29 carbon signals, 2 of them are present in the olefinic region (δ C 138.1 and 121.8 ppm), accounting for 1 degree of unsaturation. The presence of a pentacyclic carbo-structure in compound 1 was gleaned from the 13C NMR spectrum that showed 27 carbon signals appear below δ C 70.0 ppm. Distortionless enhancement by polarization transfer (DEPT) experiment characterized the carbon atoms in compound 1 into 5 methyls, 12 methylenes, 7 methines, and 5 non-protonated carbons. 1H NMR spectrum exhibited three secondary methyl groups resonating at δ H 0.91, 0.88, and 0.88 ppm and 2 tertiary methyls resonating at δ H 0.97 and 0.87 ppm. 1H, 13C NMR, and heteronuclear single quantum coherence (HSQC) experiments clarified the presence of an oxygenated methine (δ H/δ C: 3.77/67.1), an oxygenated methylene group (4.29 and 4.14/62.1), and a cyclopropyl methylene group resonating in the up-field region (0.48 and −0.07/22.2). Literature surveys on the constituents of this green alga species, Tydemania expeditionis, revealed cycloartane-type triterpenoids [7,9], diterpenoids [8], and fatty acid derivatives as frequently encountered constituents [5]. All the previous information favors the presence of a pentacyclic nor-triterpenoid carbon skeleton. 1H–1H correlation spectroscopy (COSY) confirmed the presence of an isopropyl function (proton signal resonating at δ H 1.30 ppm is correlated with signal due to 2 methyls resonating at δ H 0.88 ppm. The same methine proton (δ H 1.30 ppm) is connected with the methylene protons resonating at δ H 1.34 and 1.12 ppm which are, in turn, correlated with the oxygenated methine proton resonating at δ H 3.77 ppm. The former methine proton is linked with other methylene protons resonating at δ H 1.48 and 0.91 ppm, which are correlated with the methine proton resonating at δ H 1.70 ppm. This methine proton is correlated with a methyl proton resonating at δ H 0.91 ppm. From the previous discussion, along with the heteronuclear multiple bond correlation (HMBC) spectrum’s investigation and the published data in the literature [7,9], the side chain was concluded to be (CH3)2CHCH2CHOHCH2CHCH3– (Figure 1). The location of the side chain was deduced from the COSY correlation between proton resonating at δ H 1.70 ppm and that at δ H 1.58 ppm. The HMBC correlations show a linkage between the latter proton and the 2 quaternary carbons resonating at δ C 45.5 and 49.5 ppm and the methyl carbons at δ C 16.5, 18.3, and 18.5 ppm. The HMBC correlations observed between the low-frequency protons resonating at δ H 0.48 and −0.07 ppm and the quaternary carbon signals (δ C 29.5 and 21.7 ppm), the methine carbon signals (δ C 43.0 and 40.6 ppm), and the methylene carbon signals (δ C 34.3 and 31.9 ppm) unambiguously the location of the cyclopropyl group between C-9–C-10–C-19. The location of the second hydroxy function and the trisubstituted double bond were deduced from the HMBC correlation observed between the oxygenated methylene protons resonating at δ H 4.29 and 4.13 ppm and the carbon signals at δ C 138.1, 121.1, and 40.6 ppm. The previous discussion indicated the chemical structure of compound 1 as 29-norcycloartane-3-en-23,28-diol.

Compound 5 was isolated as colorless oily material. The molecular formula was established as C18H34O3 from the quasi-molecular ion [M–H] peak at m/z 297.2425 in the HRESIMS analysis. The obtained molecular formula suggested 2 sites of unsaturation. The IR spectrum revealed the presence of hydroxyl function (3,434 cm−1), CH (2,961 cm−1), acid carbonyl (1,715 cm−1), and a carbon-carbon double bond (1,665 cm−1). 13C NMR spectrum confirmed the presence of 18 carbon signals, 2 of them are present in the olefinic region (δ C 133.5 and 124.3 ppm), and a carboxyl group (δ C 178.3) accounted for the 2 degrees of unsaturation. The presence of a long-chain fatty acid 5 was gleaned from the 13C NMR spectrum that showed 18 carbon signals. Hence, the DEPT experiment characterized the carbon atoms in compound 5 into 1 methyl, 14 methylene carbons, 3 methine carbons including an oxygenated methine carbon resonating at δ C 70.6 ppm and a disubstituted carbon-carbon double bond, and a non-protonated carbon. 1H NMR spectrum exhibited 1 primary methyl group resonating at δ C 0.93 ppm and 2 olefinic protons resonating at δ C 5.34 and 5.10 ppm. 1H, 13C NMR, and HSQC experiments clarified the presence of an oxygenated methine (δ H/δ C: 4.10/70.6), a disubstituted carbon-carbon double bond, and a primary methyl (δ H/δ C: 0.93/13.6). From the previous discussion, compound 5 is a long-chain fatty acid of 18 carbons decorated with 1 carbon–carbon double bond and a secondary hydroxyl function. The location of these function groups was assigned from both 1H–1H COSY and HMBC spectra, where the highest field proton signal δ H 5.34 ppm is correlated with the methylene protons resonating at δ H 2.10 ppm, which are in turn correlated with the methyl function. These correlations and that in the HMBC between H (δ H 5.34 ppm) and carbon signals resonating at δ C 20.7 and 13.6 ppm confirmed the location of the double bond at C15═C16. A similar combination between 1H–1H COSY and HMBC spectra located the hydroxyl function in the b-position to the carboxyl function. From the previous position, the chemical structure of compound 5 can be concluded and identified as 3-hydroxyoctadeca-15(Z)-enoic acid (Figure 2).

The other isolated compounds were identified as 29-norcycloartane-5,24-dien-3-ol-23-one (2), 29-norcycloartane-3,24-dien-3-ol-23-one (3), and 29-norcycloartane-5,24-dien-3-ol (4), after careful comparison of their spectral data with those in the literature [7,9].

3.2 Biological activities

The antiproliferative activity of the isolated metabolites was examined against three cancer cell lines: HeLa, HepG-2, and MCF-7. Compounds 2 and 3 demonstrated a robust antiproliferative effect against all cell lines with IC50 values ranging from 17.8 ± 1.71 to 23.3 ± 1.66 µM. Compounds 1 and 4 showed a moderate antiproliferative effect against all cell lines with IC50 values ranging from 25.6 ± 2.45 to 42.7 ± 3.32 µM. Compound 5 showed a weak cytotoxic effect against all cell lines (Table 3).

Table 3

Cytotoxic effects of compounds 1–5 isolated from Tydemania expeditionis

Compound no. IC50 (µM)
HeLa HepG-2 MCF-7
1 30.9 ± 2.85 42.7 ± 3.32 30.7 ± 2.67
2 17.8 ± 1.71 19.5 ± 1.44 23.1 ± 1.66
3 20.4 ± 1.78 23.1 ± 2.00 18.0 ± 1.74
4 31.9 ± 2.23 42.0 ± 3.66 25.6 ± 2.45
5 >50.0 44.2 ± 4.04 >50.0
Doxorubicin 1.9 ± 0.04 1.8 ± 0.01 3.1 ± 0.15

Human cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG-2), and breast adenocarcinoma (MCF-7).

Data are presented as mean value ± SD; n = 6.

The antifungal activity of all isolated compounds has been tested against several fungi (Aspergillus niger, A. fumigatus, A. flavus, Candida albicans, C. tropicalis, and Fusarium oxysporum). Compounds 2–4 revealed potent inhibition against A. flavus and Fusarium oxysporum. Compounds 1–4 showed moderate to weak inhibition activity against A. niger, A. fumigatus, Candida albicans, and C. tropicalis. Compound 5 showed weak to non-detected activity against all microbes (Table 4).

Table 4

Diameter of inhibition zone in mm at concentration level of 10 µg/mL of the compounds 1–5

Comp. no. Fungi
Aspergillus flavus A. fumigatus A. niger Fusarium oxysporum Candida albicans C. tropicalis
1 11 ± 0.91 9 ± 1.00 8 ± 0.59 10 ± 0.96 8 ± 0.80 9 ± 0.76
2 14 ± 1.11 12 ± 1.13 11 ± 1.06 16 ± 1.43 11 ± 1.01 10 ± 0.97
3 11 ± 0.98 9 ± 0.66 7 ± 0.54 12 ± 1.08 10 ± 0.86 9 ± 0.78
4 15 ± 1.17 13 ± 1.00 13 ± 1.18 17 ± 1.56 12 ± 1.05 7 ± 0.68
5 7 ± 0.67 ND ND 6 ± 0.51 ND ND
Amphotricin B 29 ± 1.93 32 ± 2.38 34 ± 2.71 26 ± 2.28 28 ± 2.56 29 ± 2.64

Amphotricin B: is a standard drug.

ND: not detected.

Several literature articles clarified the role of metabolites isolated from the orders Caulerpales and Bryopsidales abundant in tropical and subtropical waters [18,19]. The tropical and subtropical waters are suitable marine environments for the growth of T. expeditionis and seaweed predators such as sea urchins and fishes. It is believed that the defense adoption of this green alga basically depends on the excretion of chemicals. Sulfated cycloartane-type triterpenes showed good inhibitory activity against VZV and CMV protease enzymes [20], anti-inflammatory [21], cytotoxicity, and antifungal activity [6,10]. Interestingly, desulfated, 29-nor, saponin-types cycloartane triterpenes, in some instances, showed even higher biological effects than the corresponding sulfated compounds [6]. Stigmastane-type steroids also contribute to the activity of T. expeditionis, (E)-stigmasta-24(28)-en-3,6-dione showed potent affinity to the androgen receptor with an IC50 value of 7.19 ± 0.45 μM. In the current work, all isolated metabolites showed cytotoxic effects against the examined cell lines, the most potent cytotoxic compounds are 2 and 3. The main apparent difference between these two compounds and the others is the presence of α,β-unsaturated carbonyl function.

Terpenoids are one of the largest class of secondary metabolites with great potency for anticancer candidates, some of which are ready to enter the clinical trial, like mipsagargin (G-202) and thapsigargin [22]. A complex mechanism is involved in the anticancer properties of cycloartane-type terpenoids. The variety of anticancer activity of terpenoids is affected by the diversity of attached functional groups in the side chain. For instance, the sulfation pattern in the glycon unit and the presence of sugar moiety of triterpenoid from various sea cucumbers determine the differences in cytotoxic properties against a wide range of cancer cells [23]. Meanwhile, the replacement of different functional group at C-26 of cycloartane-type triterpenoids from Tetragonula sapiens Cockerell significantly affects their α-inhibitory properties [24]. The antiproliferation of cycloartane-type triterpenes, like 27-hydroxymangiferolic acid, 23-hydroxymangiferolic acid, and mangiferolic acid from Trigona minor, against human pancreatic cancer cells PANC-1 is significantly affected by the presence of the –OH group at C-23 and C-27 [25]. Apart from cytotoxicity and antiproliferation, the cycloartane-type triterpenoid like cycloartan-24-ene-1α,2α,3β-triol from Commiphora myrrha is proven for its apoptosis activity against prostatic cancer PC-3 cells. The anticancer activity involves the upregulation of caspase-3, p53, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) in the cancer cell [26].

The antifungal activity of all isolated compounds has been tested against several fungi. Compounds 2–4 revealed strong inhibition against A. flavus and Fusarium oxysporum. Compounds 1–4 showed moderate to weak inhibition activity against A. niger, A. fumigatus, C. albicans, and C. tropicalis. Compound 5 showed weak to non-detected activity against all cell lines and microbes. The results indicated that norcycloartanes exhibit antifungal–antiproliferative activities, especially those with a,b-unsaturated ketones in their side chain. Like the famous antifungal drugs carvacrol, other terpenoids may alter Ca2+ transients, vacuolar and cytosolic pH, and metabolic activity of the fungi [27].

4 Conclusion

The Red Sea green alga Tydemania expeditionis is a rich source of the norcycloartane-type triterpenoids and omega-3 fatty acids. The compounds isolated from this alga exhibited antiproliferative-antifungal activity. Compounds 2 and 3 showed a strong antiproliferative activity against HeLa, HepG-2, and MCF-7 cell lines with IC50 values ranging from 17.8 ± 1.71 to 23.3 ± 1.66 µM. Compounds 2–4 demonstrated a strong inhibition against A. flavus and Fusarium oxysporum. It is expected that the whole alga might possess nutritional value due to the presence of ω-3 fatty acids.

Acknowledgments

The author is extremely grateful to Dr Serag Eldin I. Elbehairi (Department of Biology, Faculty of Science, King Khalid University) for the support while conducting the biological work.

  1. Funding information: This research received no external funding.

  2. Author contributions: All the work described in the present article was performed in its entirety by HA, as the sole author.

  3. Conflict of interest: The author states no competing interest.

  4. Ethical approval: The conducted research is not related to either human or animal use.

  5. Data availability statement: All data generated or analyzed during this study are included in this published article (and its supplementary information files).

  6. Sample availability: Samples of the compounds are available from the author.

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Received: 2022-04-21
Revised: 2022-05-31
Accepted: 2022-06-03
Published Online: 2022-09-13

© 2022 Hajer S. Alorfi, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

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  3. Assessment of using electronic portal imaging device for analysing bolus material utilised in radiation therapy
  4. A detailed investigation on highly dense CuZr bulk metallic glasses for shielding purposes
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  6. Environmental impact assesment regulation applications and their analysis in Turkey
  7. Sample age effect on parameters of dynamic nuclear polarization in certain difluorobenzen isomers/MC800 asphaltene suspensions
  8. Passenger demand forecasting for railway systems
  9. Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach
  10. Gamma, neutron, and heavy charged ion shielding properties of Er3+-doped and Sm3+-doped zinc borate glasses
  11. Bridging chiral de-tert-butylcalix[4]arenes: Optical resolution based on column chromatography and structural characterization
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https://doi.org/10.1515/chem-2022-0179
Keywords for this article
seaweeds; chromatographic isolation; spectroscopy; antiproliferation; antifungal
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Photocatalytic degradation of Rhodamine B in aqueous phase by bimetallic metal-organic framework M/Fe-MOF (M = Co, Cu, and Mg)
  3. Assessment of using electronic portal imaging device for analysing bolus material utilised in radiation therapy
  4. A detailed investigation on highly dense CuZr bulk metallic glasses for shielding purposes
  5. Simulation of gamma-ray shielding properties for materials of medical interest
  6. Environmental impact assesment regulation applications and their analysis in Turkey
  7. Sample age effect on parameters of dynamic nuclear polarization in certain difluorobenzen isomers/MC800 asphaltene suspensions
  8. Passenger demand forecasting for railway systems
  9. Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach
  10. Gamma, neutron, and heavy charged ion shielding properties of Er3+-doped and Sm3+-doped zinc borate glasses
  11. Bridging chiral de-tert-butylcalix[4]arenes: Optical resolution based on column chromatography and structural characterization
  12. Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt
  13. Comparison of the yield and purity of plasma exosomes extracted by ultracentrifugation, precipitation, and membrane-based approaches
  14. Bioactive triterpenoids from Indonesian medicinal plant Syzygium aqueum
  15. Investigation of the effects of machining parameters on surface integrity in micromachining
  16. The mesoporous aluminosilicate application as support for bifunctional catalysts for n-hexadecane hydroconversion
  17. Gamma-ray shielding properties of Nd2O3-added iron–boron–phosphate-based composites
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  19. Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt
  20. Two new polypodane-type bicyclic triterpenoids from mastic
  21. Structural, physical, and mechanical properties of the TiO2 added hydroxyapatite composites
  22. Tribological properties and characterization of borided Co–Mg alloys
  23. Studies on Anemone nemorosa L. extracts; polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies
  24. Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system
  25. Cyclic connectivity index of bipolar fuzzy incidence graph
  26. The role of passage numbers of donor cells in the development of Arabian Oryx – Cow interspecific somatic cell nuclear transfer embryos
  27. Mechanical property evaluation of tellurite–germanate glasses and comparison of their radiation-shielding characteristics using EPICS2017 to other glass systems
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  45. Texturing of nanocoatings for surface acoustic wave-based sensors for volatile organic compounds
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  72. Determination of oil composition of cowpea (Vigna unguiculata L.) seeds under influence of organic fertilizer forms
  73. Activated partial thromboplastin time maybe associated with the prognosis of papillary thyroid carcinoma
  74. Treatment of rat brain ischemia model by NSCs-polymer scaffold transplantation
  75. Lead and cadmium removal with native yeast from coastal wetlands
  76. Characterization of electroless Ni-coated Fe–Co composite using powder metallurgy
  77. Ferrate synthesis using NaOCl and its application for dye removal
  78. Antioxidant, antidiabetic, and anticholinesterase potential of Chenopodium murale L. extracts using in vitro and in vivo approaches
  79. Study on essential oil, antioxidant activity, anti-human prostate cancer effects, and induction of apoptosis by Equisetum arvense
  80. Experimental study on turning machine with permanent magnetic cutting tool
  81. Numerical simulation and mathematical modeling of the casting process for pearlitic spheroidal graphite cast iron
  82. Design, synthesis, and cytotoxicity evaluation of novel thiophene, pyrimidine, pyridazine, and pyridine: Griseofulvin heterocyclic extension derivatives
  83. Isolation and identification of promising antibiotic-producing bacteria
  84. Ultrasonic-induced reversible blood–brain barrier opening: Safety evaluation into the cellular level
  85. Evaluation of phytochemical and antioxidant potential of various extracts from traditionally used medicinal plants of Pakistan
  86. Effect of calcium lactate in standard diet on selected markers of oxidative stress and inflammation in ovariectomized rats
  87. Identification of crucial salivary proteins/genes and pathways involved in pathogenesis of temporomandibular disorders
  88. Zirconium-modified attapulgite was used for removing of Cr(vi) in aqueous solution
  89. The stress distribution of different types of restorative materials in primary molar
  90. Reducing surface heat loss in steam boilers
  91. Deformation behavior and formability of friction stir processed DP600 steel
  92. Synthesis and characterization of bismuth oxide/commercial activated carbon composite for battery anode
  93. Phytochemical analysis of Ziziphus jujube leaf at different foliar ages based on widely targeted metabolomics
  94. Effects of in ovo injection of black cumin (Nigella sativa) extract on hatching performance of broiler eggs
  95. Separation and evaluation of potential antioxidant, analgesic, and anti-inflammatory activities of limonene-rich essential oils from Citrus sinensis (L.)
  96. Bioactivity of a polyhydroxy gorgostane steroid from Xenia umbellata
  97. BiCAM-based automated scoring system for digital logic circuit diagrams
  98. Analysis of standard systems with solar monitoring systems
  99. Structural and spectroscopic properties of voriconazole and fluconazole – Experimental and theoretical studies
  100. New plant resistance inducers based on polyamines
  101. Experimental investigation of single-lap bolted and bolted/bonded (hybrid) joints of polymeric plates
  102. Investigation of inlet air pressure and evaporative cooling of four different cogeneration cycles
  103. Review Articles
  104. Comprehensive review on synthesis, physicochemical properties, and application of activated carbon from the Arecaceae plants for enhanced wastewater treatment
  105. Research progress on speciation analysis of arsenic in traditional Chinese medicine
  106. Recent modified air-assisted liquid–liquid microextraction applications for medicines and organic compounds in various samples: A review
  107. An insight on Vietnamese bio-waste materials as activated carbon precursors for multiple applications in environmental protection
  108. Antimicrobial activities of the extracts and secondary metabolites from Clausena genus – A review
  109. Bioremediation of organic/heavy metal contaminants by mixed cultures of microorganisms: A review
  110. Sonodynamic therapy for breast cancer: A literature review
  111. Recent progress of amino acid transporters as a novel antitumor target
  112. Aconitum coreanum Rapaics: Botany, traditional uses, phytochemistry, pharmacology, and toxicology
  113. Corrigendum
  114. Corrigendum to “Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt”
  115. Corrigendum to “Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach”
  116. Corrigendum to “Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt”
  117. Corrigendum to “Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry”
  118. Corrigendum to “Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system”
  119. Erratum
  120. Erratum to “Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies”
  121. Special Issue on Applied Biochemistry and Biotechnology (ABB 2021)
  122. Study of solidification and stabilization of heavy metals by passivators in heavy metal-contaminated soil
  123. Human health risk assessment and distribution of VOCs in a chemical site, Weinan, China
  124. Preparation and characterization of Sparassis latifolia β-glucan microcapsules
  125. Special Issue on the Conference of Energy, Fuels, Environment 2020
  126. Improving the thermal performance of existing buildings in light of the requirements of the EU directive 2010/31/EU in Poland
  127. Special Issue on Ethnobotanical, Phytochemical and Biological Investigation of Medicinal Plants
  128. Study of plant resources with ethnomedicinal relevance from district Bagh, Azad Jammu and Kashmir, Pakistan
  129. Studies on the chemical composition of plants used in traditional medicine in Congo
  130. Special Issue on Applied Chemistry in Agriculture and Food Science
  131. Strip spraying technology for precise herbicide application in carrot fields
  132. Special Issue on Pharmacology and Metabolomics of Ethnobotanical and Herbal Medicine
  133. Phytochemical profiling, antibacterial and antioxidant properties of Crocus sativus flower: A comparison between tepals and stigmas
  134. Antioxidant and antimicrobial properties of polyphenolics from Withania adpressa (Coss.) Batt. against selected drug-resistant bacterial strains
  135. Integrating network pharmacology and molecular docking to explore the potential mechanism of Xinguan No. 3 in the treatment of COVID-19
  136. Chemical composition and in vitro and in vivo biological assortment of fixed oil extracted from Ficus benghalensis L.
  137. A review of the pharmacological activities and protective effects of Inonotus obliquus triterpenoids in kidney diseases
  138. Ethnopharmacological study of medicinal plants in Kastamonu province (Türkiye)
  139. Protective effects of asperuloside against cyclophosphamide-induced urotoxicity and hematotoxicity in rats
  140. Special Issue on Essential Oil, Extraction, Phytochemistry, Advances, and Application
  141. Identification of volatile compounds and antioxidant, antibacterial, and antifungal properties against drug-resistant microbes of essential oils from the leaves of Mentha rotundifolia var. apodysa Briq. (Lamiaceae)
  142. Phenolic contents, anticancer, antioxidant, and antimicrobial capacities of MeOH extract from the aerial parts of Trema orientalis plant
  143. Chemical composition and antimicrobial activity of essential oils from Mentha pulegium and Rosmarinus officinalis against multidrug-resistant microbes and their acute toxicity study
  144. Special Issue on Marine Environmental Sciences and Significance of the Multidisciplinary Approaches
  145. An insightful overview of the distribution pattern of polycyclic aromatic hydrocarbon in the marine sediments of the Red Sea
  146. Antifungal–antiproliferative norcycloartane-type triterpenes from the Red Sea green alga Tydemania expeditionis
  147. Solvent effect, dipole moment, and DFT studies of multi donor–acceptor type pyridine derivative
  148. An extensive assessment on the distribution pattern of organic contaminants in the aerosols samples in the Middle East
  149. Special Issue on 4th IC3PE
  150. Energetics of carboxylic acid–pyridine heterosynthon revisited: A computational study of intermolecular hydrogen bond domination on phenylacetic acid–nicotinamide cocrystals
  151. A review: Silver–zinc oxide nanoparticles – organoclay-reinforced chitosan bionanocomposites for food packaging
  152. Green synthesis of magnetic activated carbon from peanut shells functionalized with TiO2 photocatalyst for Batik liquid waste treatment
  153. Coagulation activity of liquid extraction of Leucaena leucocephala and Sesbania grandiflora on the removal of turbidity
  154. Hydrocracking optimization of palm oil over NiMoO4/activated carbon catalyst to produce biogasoline and kerosine
  155. Special Issue on Pharmacology and metabolomics of ethnobotanical and herbal medicine
  156. Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ
  157. Special Issue on The 1st Malaysia International Conference on Nanotechnology & Catalysis (MICNC2021)
  158. Surfactant evaluation for enhanced oil recovery: Phase behavior and interfacial tension
  159. Topical Issue on phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  160. Phytochemical analysis of leaves and stems of Physalis alkekengi L. (Solanaceae)
  161. Phytochemical and pharmacological profiling of Trewia nudiflora Linn. leaf extract deciphers therapeutic potentials against thrombosis, arthritis, helminths, and insects
  162. Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain
  163. Protective effect of Allium atroviolaceum-synthesized SeNPs on aluminum-induced brain damage in mice
  164. Mechanism study of Cordyceps sinensis alleviates renal ischemia–reperfusion injury
  165. Plant-derived bisbenzylisoquinoline alkaloid tetrandrine prevents human podocyte injury by regulating the miR-150-5p/NPHS1 axis
  166. Network pharmacology combined with molecular docking to explore the anti-osteoporosis mechanisms of β-ecdysone derived from medicinal plants
  167. Chinese medicinal plant Polygonum cuspidatum ameliorates silicosis via suppressing the Wnt/β-catenin pathway
  168. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part I
  169. Investigation of improved optical and conductivity properties of poly(methyl methacrylate)–MXenes (PMMA–MXenes) nanocomposite thin films for optoelectronic applications
  170. Special Issue on Applied Biochemistry and Biotechnology (ABB 2022)
  171. Model predictive control for precision irrigation of a Quinoa crop
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