Russel S. Ramsewak

Cytotoxicity, antioxidant and anti-inflammatory activities of Curcumins I–III from Curcuma longa

Curcumin I, curcumin II (monodemethoxycurcumin) and curcumin III (bisdemethoxycurcumin) from Curcuma longa were assayed for their cytotoxicity, antioxidant and anti-inflammatory activities. These compounds showed activity against leukemia, colon, CNS, melanoma, renal, and breast cancer cell lines. The inhibition of liposome peroxidation by curcumins I-III at 100 microg/ml were 58, 40 and 22%, respectively. The inhibition of COX-I and COX-II enzymes by the curcumins was observed. Curcumins I-III were active against COX-I enzyme at 125 microg/ml and showed 32, 38.5 and 39.2% inhibition of the enzyme, respectively. Curcumins I-III also showed good inhibition of the COX-II enzyme at 125 mg/ml with 89.7, 82.5 and 58.9% inhibition of the enzyme, respectively.

Bioactive N-isobutylamides from the flower buds of Spilanthes acmella

The hexane extract of dried flower buds of Spilanthes acmella afforded three N-isobutyl amides: spilanthol, undeca-2E,7Z,9E-trienoic acid isobutylamide and undeca-2E-en-8,10-diynoic acid isobutylamide. Their structures were determined by 1H and 13C NMR, MS and GC-MS spectroscopic methods. All were active against Aedes aegyptii larvae and Helicoverpa zea neonates at 12.5 and 250 micrograms/mL concentrations, respectively.

Antitumour and anticarcinogenic activity of Phyllanthus amarus extract

Aqueous extract of Phyllanthus amarus (P. amarus) treatment exhibited potent anticarcinogenic activity against 20-methylcholanthrene (20-MC) induced sarcoma development and increased the survival of tumour harboring mice. The extract administration (p.o) was also found to prolong the life span of Daltons Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) bearing mice and reduced the volume of transplanted solid tumours. The extract inhibited aniline hydroxylase, a P-450 enzyme. The concentration required for 50% inhibition (IC(50)) was found to be 540 microg/ml. The extract was found to inhibit DNA topoisomerase II of Saccharomyces cerevisiae mutant cell cultures and inhibited cell cycle regulatory enzyme cdc25 tyrosine phosphatase (IC(50-25) microg/ml). Antitumour and anticancer activity of P. amarus may be related with the inhibition of metabolic activation of carcinogen as well as the inhibition of cell cycle regulators and DNA repair.

Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots

Cyclooxygenase enzyme inhibitory assay-guided purification of ethyl acetate extract of Piper methysticum (kava kava) roots yielded six biologically active compounds (1-7), which were purified using MPLC, preparative TLC and HPLC methods. These compounds were also evaluated for antioxidant activities. Dihydrokawain (1) and yangonin (6) showed the highest COX-I and COX-II inhibitory activities at 100 microg/ml, respectively. The lipid oxidation assay did not reveal antioxidant activities for demethoxyangonin (2), dihydrokawain (1), kawain (4), dihydromethysticin (5) or methysticin (7) at 50 microg/ml. The antioxidant activities of flavokawain A (3) and yangonin (6) could not be tested in the lipid oxidation assay due to solubility problems. However, yangonin and methysticin showed moderate antioxidant activities in the free radical scavenging assay at 2.5 mg/ml.

Briarane and asbestinane diterpenes from Briareum asbestinum

Abstract Six new diterpenes, (1–3 and 5–7), were isolated from Briareum asbestinum collected off the coast of Tobago, West Indies. Their structures were determined by a combination of 2D NMR experiments.

Further briareolate esters and briareolides from the Caribbean gorgonian octocoral Briareum asbestinum

Abstract Eight new diterpenes were isolated from Briareum asbestinum collected off south-west Tobago. Six metabolites (4) – (9) are briareolate esters while (10) and (11) are related to the briareolides. The structures of all compounds were determined by 2D NMR spectroscopy and correlation with known compounds. The structure of compound 4 was confirmed by X-ray analysis. Compounds 4, 7, 9 and 11 showed weak activity in the brine shrimp bioassay.

Variable-Temperature 1H-NMR Studies on Two C-Glycosylflavones

Two known C-glycosylflavones, swertisin and embinoidin, were isolated from the leaves of Anthurium aripoense, and characterized by room temperature 1D and 2D NMR experiments. At this temperature, the 1H- and 13C-NMR spectra of these C-glycosylflavones revealed doubling of signals, which suggested the presence of two rotamers in solution. Variable-temperature (VT) 1H-NMR studies supported this hypothesis. The T-ROESY data, in addition to the theoretical (MM2) calculations utilizing the Chem3D Pro software, confirmed the hypothesis that the two rotamers interchange via rotation about the C-glycosidic bond.

Identification of new limonoids from Swietenia and their biological activity against insects.

BACKGROUND Natural limonoids are one group of compounds being studied for their insecticidal properties. To discover new limonoids with better activities, analogs were prepared via acylation and hydrolysis, and bioassayed. RESULTS Analogs were identified using one- and two-dimensional (COSY, HMQC and HMBC) (1) H and (13) C NMR, IR and MS. 3-O-Isovalerylswietenolide (13) and 3-O-isobutyrylswietenolide (14) showed excellent antifeedant activity, with DC(50) values of 0.19 and 0.009 mg L(-1) respectively, compared with the natural limonoid swietenolide (80.6 mg L(-1) ) against fourth-instar Spodoptera frugiperda (JE Smith) larvae. CONCLUSION This work shows that limonoid analogs prepared through semi-synthesis can be used as lead compounds for the development of new insecticides.

Toxicity–structure activity evaluation of limonoids from Swietenia species on Artemia salina

Context: Many plant extracts and compounds are being investigated for their cytotoxicity and hence their medicinal or therapeutic properties. Reports of toxicity studies with limonoid analogs have been sparse and have involved mainly crude extracts. In this study, individual natural limonoids have been isolated and their toxicity manipulated via semisynthesis. Objective: The lethality of limonoid analogs from Swietenia macrophylla King and Swietenia aubrevilleana Stehlé & Cusin (Meliaceae) against Artemia salina Leach was determined. Materials and methods: Four known natural limonoids were isolated from the dry ground seeds of S. macrophylla and S. aubrevilleana, modified using acylation and hydrolysis reactions and tested in A. salina lethality assays at 1–400 ppm. A 50% lethal concentration (LC50) was determined by probit analysis. Results: Higher levels of toxicity were achieved in most of the prepared analogs compared with the parent natural limonoids. The compound showing the highest toxicity with LC50 3.9 ppm was 3-O-benzoyl-3-detigloylisoswietenine (20). Other analogs with high toxicity were 6-O-benzoylswietenolide (7), 6-O-benzoylswietenine (17), and 3,6-O,O-dipropionylswietenolide (9), which showed LC50 values of 4.3, 7.5, and 28.5 ppm, respectively. Discussion and conclusions: Toxicity can be improved via semisynthesis. The compounds exhibiting high toxicity (low LC50) may be good candidates for cytotoxicity studies.

The Use of Coupled HSQC Spectra to Aid in Stereochemical Assignments of Molecules with Severe Proton Spectral Overlap

INTRODUCTION A simple glycoside with only 13 carbons exhibited extensive overlapping of four of the glycosidic protons, causing extreme difficulty in the determination of the stereochemistry of the pyranose unit. However, acquisition of a high-resolution coupled heteronuclear single-quantum coherence (HSQC) spectrum overcame this problem. This spectrum provides a useful method for determining vicinal proton coupling constants between strongly coupled protons. OBJECTIVE To show the potential of high-resolution coupled HSQC spectra in overcoming spectral overlap. METHODOLOGY The sample was obtained by methanol extraction, followed by fractionation and column chromatography of the dried leaves of Montrichardia arborescens (Araceae). NMR spectra were obtained on 1.5 mg of sample dissolved in 120 μL of CD₃OD containing 0.1% trimethylsilyl (TMS) as internal standard. A gradient-selected HSQC spectrum was obtained using standard Varian library pulse sequences in phase sensitive mode. The high-resolution coupled HSQC spectrum focused on the saccharide region with a 1025 Hz ¹H spectral window, a 6300 Hz ¹³C spectral window, 1024 data points, a 0.3 Hz relaxation delay, 384 time increments (linear predicted to 4096), and 80 scans per time increment. RESULTS The use of a high-resolution coupled HSQC spectrum allowed determination of the coupling patterns of the various pyranose protons with sufficient accuracy. This enabled completion of the assignments and identification of the pyranose unit as glucose. CONCLUSION The study has shown the effectiveness of the use of a high-resolution coupled HSQC spectrum in the assignment of molecules with severe spectral overlap.