MyMedR

Displaying publications 21 - 29 of 29 in total

Abstract:

Sort:

Bioassay-guided isolation of a sesquiterpene lactone of deoxyelephantopin from Elephantopus scaber Linn. active on Trypanosome brucei rhodesience

Zahari Z, Jani NA, Amanah A, Latif MN, Majid MI, Adenan MI

Phytomedicine, 2014 Feb 15;21(3):282-5.
PMID: 24269185 DOI: 10.1016/j.phymed.2013.09.011

Methanolic extracts of 70 Malaysia plants were screened for their in vitro antitrypanosomal activity using Trypanosome brucei rhodesience, strain STIB 900 and mouse skeletal cell (L-6) in cytotoxicity activity assay. Results indicated that methanol extract from Elephantopus scaber Linn. (E. scaber) possessed the highest value of antitrypanosomal activity with good selectivity index (antitrypanosomal IC50 of 0.22±0.02 μg/ml, SI value of 204.55). Based on these results, E. scaber was chosen for further study by applying bioassay guided fractionation to isolate its antiprotozoal principle. The antiprotozoal principle was isolated from the ethyl acetate partition through solvent fractionation and crystallization process. The isolated active compound 1 was identified as deoxyelephantopin on the basis of its spectral analysis (FTIR, MS, 1D and 2D NMR).

Matched MeSH terms: Lactones/pharmacology*
Novel halogenated metabolites from the Malaysian Laurencia pannosa

Suzuki M, Daitoh M, Vairappan CS, Abe T, Masuda M

J Nat Prod, 2001 May;64(5):597-602.
PMID: 11374951

In connection with our chemotaxonomic studies of Malaysian species of the red algal genus Laurencia, the chemical composition of Laurencia pannosa Zanardini was examined. Two halogenated sesquiterpenoids, named pannosanol (1) and pannosane (2), have been isolated along with a halogenated C15-acetogenin, (3Z)-chlorofucin (3). The structures of these compounds were determined from their spectroscopic data (IR, 1H NMR, 13C NMR, 2D NMR, and MS). Pannosanol and pannosane are novel halometabolites with an unusual rearranged chamigrane framework. Antibacterial activities of these metabolites against marine bacteria are also described.

Matched MeSH terms: Lactones/pharmacology*
Fulltext Modulation of cancer signalling pathway(s) in two -stage mouse skin tumorigenesis by annonacin

Md Roduan MR, Abd Hamid R, Mohtarrudin N

BMC Complement Altern Med, 2019 Sep 03;19(1):238.
PMID: 31481122 DOI: 10.1186/s12906-019-2650-1

BACKGROUND: Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved.
METHODS: Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin.
RESULTS: With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis.
CONCLUSIONS: Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.

Matched MeSH terms: Lactones/pharmacology*
The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression

Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML

Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011

Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.

Matched MeSH terms: Lactones/pharmacology*
Antifungal garcinia acid esters from the fruits of Garcinia atroviridis

Mackeen MM, Ali AM, Lajis NH, Kawazu K, Kikuzaki H, Nakatani N

Z Naturforsch C J Biosci, 2002 6 18;57(3-4):291-5.
PMID: 12064729

Two new garcinia acid derivatives, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide and 1',1"-dibutyl methyl hydroxycitrate, were isolated from the fruits of Garcinia atroviridis guided by TLC bioautography against the fungus Cladosporium herbarum. The structures of these compounds were established by spectral analysis. The former compound represents a unique beta-lactone structure and the latter compound is most likely an artefact of garcinia acid (= hydroxycitric acid). Both compounds showed selective antifungal activity comparable to that of cycloheximide (MID: 0.5 microg/spot) only against C herbarum at the MIDs of 0.4 and 0.8 microg/spot but were inactive against bacteria (Bacillus subtilis, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli), other fungi (Alternaria sp., Fusarium moniliforme and Aspergillus ochraceous) including the yeast Candida albicans.

Matched MeSH terms: Lactones/pharmacology
Fulltext Clitorienolactones and Isoflavonoids of Clitorea ternatea Roots Alleviate Stress-Like Symptoms in a Reserpine-Induced Zebrafish Model

Ngadni MA, Akhtar MT, Ismail IS, Norazhar AI, Lee SY, Maulidiani M, et al.

Molecules, 2021 Jul 07;26(14).
PMID: 34299411 DOI: 10.3390/molecules26144137

Clitorea ternatea has been used in Ayurvedic medicine as a brain stimulant to treat mental illnesses and mental functional disorders. In this study, the metabolite profiles of crude C. ternatea root extract (CTRE), ethyl acetate (EA), and 50% aqueous methanol (50% MeOH) fractions were investigated using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UHPLC-DAD-MS/MS), while their effect on the stress-like behavior of zebrafish, pharmacologically induced with reserpine, was investigated. A total of 32 compounds were putatively identified, among which, a series of norneolignans, clitorienolactones, and various flavonoids (flavone, flavonol, isoflavone, and isoflavanone) was found to comprise the major constituents, particularly in the EA and 50% MeOH fractions. The clitorienolactones, presently unique to the species, were present in both the free and glycosylated forms in the roots. Both the EA and 50% MeOH fractions displayed moderate effects on the stress-induced zebrafish model, significantly decreasing freezing duration and elevating the total distance travelled and average velocity, 72 h post-treatment. The results of the present study provide further evidence that the basis for the use of C. ternatea roots in traditional medicine to alleviate brain-related conditions, such as stress and depression, is attributable to the presence of clitorienolactones and the isoflavonoidal constituents.

Matched MeSH terms: Lactones/pharmacology*
New flavan and alkyl alpha,beta-lactones from the stem bark of Horsfieldia superba

Al-Mekhlafi NA, Shaaria K, Abas F, Jeyaraj EJ, Stanslas J, Khalivulla SI, et al.

Nat Prod Commun, 2013 Apr;8(4):447-51.
PMID: 23738449

In the present study phytochemical investigation of the methanol extract of the stem bark of Horsfieldia superba led to the isolation of twenty compounds (1-20), of which three (1-3) were new. However, compounds 2 and 3 were previously reported as synthetic alpha,beta-lactones. The compounds were characterized as (-)-3,4',7-trihydroxy-3'-methoxyflavan (1), (-)-5,6-dihydro-6-undecyl-2H-pyran-2-one (2), and (-)-5,6-dihydro-6-tridecyl-2H-pyran-2-one (3). Seventeen other known compounds were also isolated and identified as (-)-viridiflorol (4), hexacosanoic acid (5), beta-sitosterol (6), methyl 2,4-dihydroxy-6-methylbenzoate (methylorsellinate) (7), methyl 2,4-dihydroxy-3,6-dimethylbenzoate (8), (-)-4'-hydroxy-7-methoxyflavan (9), (-)-4',7-dihydroxyflavan (10), (-)-4',7-dihydroxy-3'-methoxyflavan (11), (+)-3,4',7-trihydroxyflavan (12), (-)-catechin (13), (-)-epicatechin (14), (-)-7-hydroxy-3',4'-methylenedioxyflavan (15), 2',3,4-trihydroxy-4'-methoxydihydrochalcone (16), 3',4',7-trihydroxyflavone (17), (+)-4'-hydroxy-7-methoxyflavanone (18), hexadecanoic acid (palmitic acid) (19) and 3,4-dihydroxybenzoic acid (20). The structures of the compounds were fully characterized by various physical methods (melting point, optical rotation), spectral (UV, IR, ID and 2D NMR) and mass spectrometric techniques. In vitro assay of compounds 2 and 3 demonstrated moderate cytotoxic activities against human prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cells, while the chloroform and ethyl acetate fractions of H. superba were found to exhibit moderate AChE inhibitory activity (IC50 72 and 60 microg/mL).

Matched MeSH terms: Lactones/pharmacology
Cytotoxic prenylated depsidones from Garcinia parvifolia

Xu YJ, Chiang PY, Lai YH, Vittal JJ, Wu XH, Tan BK, et al.

J Nat Prod, 2000 Oct;63(10):1361-3.
PMID: 11076552

Leaf extracts of Garcinia parvifolia provided relatively high yields of four novel, cytotoxic prenylated depsidones. The structures were determined mainly by detailed NMR spectral analysis and X-ray crystallography.

Matched MeSH terms: Lactones/pharmacology*
Goniolanceolatins A-H, Cytotoxic Bis-styryllactones from Goniothalamus lanceolatus

Bihud NV, Rasol NE, Imran S, Awang K, Ahmad FB, Mai CW, et al.

J Nat Prod, 2019 09 27;82(9):2430-2442.
PMID: 31433181 DOI: 10.1021/acs.jnatprod.8b01067

Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,β-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 μM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.

Matched MeSH terms: Lactones/pharmacology*