A novel proaporphine-tryptamine dimer alkaloid, named phoebegrandine C 1, was isolated from the leaves of Phoebe grandis (Nees) Merr. Its structural elucidation was carried out using spectroscopic techniques, notably 2D NMR.
Plant cell culture technology is potentially useful in producing high-valued secondary metabolites. Eurycoma longifolia root extracts are consumed as a health tonic but more popularly used as an aphrodisiac. Studies on the aphrodisiac properties and the possible compounds involved have been widely studied. There are many potentially useful compounds reported from the root extracts of E. longifolia. However, studies on the in vitro production of useful compounds from this plant have not been reported. This chapter will describe methods of callus induction and extraction of 9-methoxycanthin-6-one from E. longifolia Jack explants with emphasis on the tap and fibrous roots. This compound, known to have anti-tumour activity, is present in intact plant parts and in callus tissues of different explants.
Serotonin (5-HT) antagonists and reuptake inhibitors (SARIs) are atypical antidepressants for managing major depressive disorder. They are oftentimes applied as adjuvants for ameliorating aftereffects of SSRI antidepressants including insomnia and sexual dysfunction. The few available candidates of this class including lorpiprazole and trazodone also display some daunting side effects, making a continuous search for improved alternatives essential. Natural β-carboline alkaloids (NβCs) are interestingly renowned with broad pharmacological spectrum against several neuropsychiatric disorders including depression. However, their potentials as SARIs remain underexplored. In this study, 982 NβCs retrieved from the Ambinter-Greenpharma (Amb) database were virtually screened for potent SARI alternatives using computational and biocheminformatics approaches: homology modelling of 5-HT1A receptor, Glide HTVS, SP and XP molecular docking, molecular dynamics (MD) simulation, ADMET and mutagenicity predictions. The homology receptor was validated as a good representative of human 5HT1A receptor using the RCSB structure validation and quality protocols. From the virtual screening against the 5-HT1A receptor, Amb ligands, Amb18709727 and Amb37857532 showed higher binding affinities by XP scores of -8.725 and -7.976 kcal/mol, and MMGBSA of -87.972 and -107.585 kcal/mol respectively compared to lorpiprazole, a reference SARI with XP score and MMGBSA of -6.512 and -62.788 kcal/mol respectively. They maintained ideal contacts with pharmacologically essential amino acid residues implicated in SARI mechanisms and expressed higher stability and compactness than lorpiprazole throughout the trajectories of 100 ns MD simulation. They also displayed interesting ADME, druggability, low toxicity and mutagenicity profiles, ideal for CNS drug prospects, thus, recommended as putative SARI candidates for further study.Communicated by Ramaswamy H. Sarma.
The methanol, n-butanol, chloroform and water extracts obtained from the root of Eurycoma longifolia Jack were assayed using methylene blue assay to evaluate its cytotoxic effect against KB, DU-145, RD, MCF-7, CaOV-3, MDBK cell lines. The results showed that all the root extracts except the water extract of E. longifolia produced significant cytotoxic effect on these cell lines. However, no significant cytotoxic effect was detected on MDBK (kidney) normal cell line. 9-methoxycanthin-6-one, an alkaloid, was detected in each extract with different intensities by reversed-phase high performance liquid chromatography.
Sildenafil and its analogues (tadalafil and vardenafil) are phosphodiesterase type 5 inhibitors used in the treatment of male erectile dysfunction. Some dietary supplements, herbal preparations and food products which claim to enhance male sexual function have been found to be adulterated with these drugs. In this study, a gas chromatograph-mass spectrometer (GC-MS) assay was developed for identification of the drugs. In addition to good and short chromatographic separation that can be achieved within 6 min by using a short 10 m capillary column, no prior sample clean-up before GC-MS analysis was required, thus making this assay a cost saving and rapid method. Furthermore, the assay is specific as the identification of sildenafil, tadalafil and vardenafil were done by detection of molecular ions; m/z 474, 389 and 488, [corrected] respectively, and several other characteristic ions resulted from the mass fragmentation of individual molecules. Using our currently developed assay, sildenafil and its analogues were successfully identified in food and herbal matrices.
A phytochemical study on the bark of Neisosperma oppositifolia (Apocynaceae) yielded two new beta-carboline indole alkaloids, oppositinines A (1) and B (2), together with five known alkaloids, isoreserpiline, isocarapanaubine, vobasine, 10-methoxydihydrocorynantheol-N-oxide, and ochropposinine oxindole. Structural elucidation of 1 and 2 was performed using 2D NMR methods. Oppositinines A (1) and B (2) showed potent vasorelaxant effects on the rat aorta.
The present study was focused to investigate the effect of selected spices (turmeric, torch ginger, lemongrass and curry leaves) on the formation of heterocyclic amines (HCAs, IQx, MeIQ, MeIQx, DiMeIQx, IQ, harman, norharman, and AαC) in deep fried lamb meat. Meat samples were marinated with optimized levels of turmeric (4 %), 10 % each of torch ginger, lemon grass, curry leaves at medium (70 °C) and well done (80 °C) doneness temperatures. The concentration of HCAs in deep fried meat samples were analysed using LC-MS/MS technique. The results revealed that torch ginger (10 %) has reduced 74.8 % of Me1Qx (1.39 to 0.35 ng/g) at medium doneness, followed by the 64.7 % reduction, using curry leaves and turmeric at medium degree of doneness. Torch ginger has reduced 86.6 % of AαC (2.59 to 0.40 ng/g) at well done doneness. The most prevalence level of HCAs was found in deep fried meat i.e. DiMeIQ (3.69 ng/g) at well done doneness. The sensory evaluation, using a 7 point hedonic test design for colour and texture in deep fried meat samples were resulted in a preferred color of golden brown and slightly tough texture. The use of local spices in marinating of deep fried lamb meat samples will certainly inhibit/reduce the level of these toxic and harmful HCAs.
A series of benzimidazole-based N-heterocyclic carbene (NHC) proligands {1-benzyl-3-(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (1/4), 1,3-bis(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (2/5) and 1,3-bis(3-(2-methylbenzyl)-benzimidazolium-1-ylmethylbenzene dibromide/dihexafluorophosphate (3/6)} has been synthesized by the successive N-alkylation method. Ag complexes {1-benzyl-3-(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (7), 1,3-bis(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (8) and 1,3-bis(3-(2-methylbenzyl)-benzimidazol-2-ylidene)-1-ylmethylbenzene disilver(I) dihexafluorophosphate (9)} of NHC ligands have been synthesized by the treatment of benzimidazolium salts with Ag2O at mild reaction conditions. Both, NHC proligands and Ag-NHC complexes have been characterized by (1)H and (13)C{(1)H} NMR and FTIR spectroscopy and elemental analysis technique. Additionally, the structure of the NHC proligand 5 and the mononuclear Ag complexes 7 and 8 has been elucidated by the single crystal X-ray diffraction analysis. Both the complexes exhibit the same general structural motif with linear coordination geometry around the Ag centre having two NHC ligands. Preliminary in vitro antibacterial potentials of reported compounds against a Gram negative (Escherichia coli) and a Gram positive (Bacillus subtilis) bacteria evidenced the higher activity of mononuclear silver(I) complexes. The anticancer studies against the human derived colorectal cancer (HCT 116) and colorectal adenocarcinoma (HT29) cell lines using the MTT assay method, revealed the higher activity of Ag-NHC complexes. The benzimidazolium salts 4-6 and Ag-NHC complexes 7-9 displayed the following IC50 values against the HCT 116 and HT29 cell lines, respectively, 31.8 ± 1.9, 15.2 ± 1.5, 4.8 ± 0.6, 10.5 ± 1.0, 18.7 ± 1.6, 1.20 ± 0.3 and 245.0 ± 4.6, 8.7 ± 0.8, 146.1 ± 3.1, 7.6 ± 0.7, 5.5 ± 0.8, 103.0 ± 2.3 μM.
The aim of this study was to assess the inhibitory effects of Sonchus olearleu extract on the generation of heterocyclic amines in roasted pork patties cooked by pan-frying. All samples were cooked for two different durations (45 min and 105 min) under 200 °C and 230 °C. 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-ami- no-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinox-aline (4,8-DiMeIQx), harman, and norharman were detected and quantified. In patties cooked at 230 °C for 105 min, S. olearleu extract (0.5%) significantly inhibited the formation of IQ, harman, and norharman by 39%, 67%, and 63%, respectively. In contrast to IQ, the levels of harman and norharman were significantly reduced by the extracts tested. However, no such effects were observed for MeIQx and 4, 8-DiMeIQx. Notably, the inhibitory effect on heterocyclic amines is significantly correlated with the antioxidant potential and total phenolic content of S. olearleu extract.
β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial, antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms. This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism of action is also added.
Natural antioxidants in spices and herbs have attracted considerable attention as potential inhibitors against the formation of mutagenic heterocyclic amines (HCAs) in heat-processed meat. In this study, the inhibitory activity of four spices/herbs and their mixtures on HCAs formation in grilled beef were examined. A simplex centroid mixture design with four components comprising turmeric, curry leaf, torch ginger and lemon grass in 19 different proportions were applied on beef samples before grilling at 240 ºC for 10 min. The HCAs were extracted from the samples using solid phase extraction (SPE) method and analysed using Liquid chromatography mass spectrometry LC-MS/MS. All spices/herbs in single or mixture forms were found to reduce total HCA concentrations in marinated grilled beef ranging from 21.2% for beef marinated with curry leaf to 94.7% for the combination of turmeric and lemon grass (50:50 w/w). At the optimum marinade formula (turmeric: lemon grass 52.4%: 47.6%), concentration of 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Harman, Norharman and AαC were 2.2, 1.4, 0.5, 2.8 and 1.2 ng/g, respectively. The results of the mutagenic activity demonstrated that this optimised marinade formula significantly (p
The effluent discharge treatment for controlling the environment from non biodegradable metal contaminants using plant extract is an efficient technique. The reduction of hexavalent chromium by abundantly available weed, Aerva lanata L. was investigated using batch equilibrium technique. The variables studied were Cr(VI) concentration, Aerva lanata L. dose, contact time, pH, temperature and agitation speed. Cyclic voltammetry and ICP-MS analysis confirmed the reduction of Cr(VI) to Cr(III). Electrochemical analysis proved that, the chromium has not been degraded and the valency of the chromium has only been changed. ICP-MS analysis shows that 100ng/L of hexavalent chromium was reduced to 97.01ng/L trivalent chromium. These results suggest that components present in the Aerva lanata L. are responsible for the reduction of Cr(VI) to Cr(III). The prime components ferulic acid, kaempherol and β-carboline present in the Aerva lanata L. may be responsible for the reduction of Cr(VI) as evident from LC-MS analysis.
A new and simple HPLC method using fluorescence detection was developed to determine 9-methoxycanthin-6-one, an active compound of Eurycoma longifolia Jack in rat and human plasma. The method entailed direct injection of plasma sample after deproteinization using acetonitrile. The mobile phase comprised acetonitrile and distilled water (55 : 45, v/v). Analysis was run at a flow rate of 1.0 ml/min with the detector operating at an excitation wavelength of 371 nm and emission wavelength of 504 nm. The method was specific and sensitive with a detection limit of 0.6 ng/ml and a quantification limit of approximately 1.6 ng/ml. The method was applied in a pilot pharmacokinetic/bioavailability study of the compound in rats. Less than 1 % of the compound was found to be absorbed orally.
Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.