NMR-based stability evaluation of (E)-1-(3',4'-dimethoxyphenyl)butadiene (DMPBD) from Zingiber cassumunar Roxb. rhizome.

INTRODUCTION: The active compound (E)-1-(3',4'-dimethoxyphenyl)butadiene (DMPBD) isolated from the rhizomes of Zingiber cassumunar Roxb. has potent anti-inflammatory and anticancer activities. Although DMPBD is one of the promising drug candidates for phytomedicine, its limited stability impedes its widespread use. For the development of new drugs, the assessment of their chemical stability is essential, ensuring they maintain their properties within specified limits throughout the period from production until use. OBJECTIVE: In the present study, we aimed to evaluate the stability of DMPBD under various conditions, including different solvents, temperatures, and lighting conditions, to identify the factors affecting stability and optimize the storage and handling conditions. METHODOLOGY: DMPBD samples subjected to the different conditions tested were monitored by quantitative 1H NMR (qHNMR), using an internal standard for the determination of the absolute quantity of DMPBD as a function of time and the changes thereof within 1 month. RESULTS: Significant decomposition of DMPBD was observed in chloroform-d1, whereas its content remained constant in methanol-d4. The content of DMPBD was maintained upon storage at temperatures below 4°C, both as methanolic solution and in the crude extract. Exposure to light had a slight negative impact on its contents. Some degradation products could be identified as resulting from O2-induced cleavage of the diene moiety. CONCLUSIONS: For pharmacological/therapeutic applications, DMPBD should be stored in the form of the crude extract or as a purified material in methanolic solution. Ideally, the storage temperature should be below 4°C and O2 should be excluded.

Computational Analysis and Biological Activities of Oxyresveratrol Analogues, the Putative Cyclooxygenase-2 Inhibitors.

Polyphenols are a large family of naturally occurring phytochemicals. Herein, oxyresveratrol was isolated from ethanolic crude extracts of Artocarpus lacucha Buch.-Ham., and chemically modified to derive its lipophilic analogues. Biological screening assays showed their inhibitory potency against cyclooxygenase-2 (COX-2) with very low cytotoxicity to the MRC-5 normal cell lines. At the catalytic site of COX-2, docking protocols with ChemPLP, GoldScore and AutoDock scoring functions were carried out to reveal hydrogen bonding interactions with key polar contacts and hydrophobic pi-interactions. For more accurate binding energetics, COX-2/ligand complexes at the binding region were computed in vacuo and implicit aqueous solvation using M06-2X density functional with 6-31G+(d,p) basis set. Our computational results confirmed that dihydrooxyresveratrol (4) is the putative inhibitor of human COX-2 with the highest inhibitory activity (IC50 of 11.50 ± 1.54 µM) among studied non-fluorinated analogues for further lead optimization. Selective substitution of fluorine provides a stronger binding affinity; however, lowering the cytotoxicity of a fluorinated analogue to a normal cell is challenging. The consensus among biological activities, ChemPLP docking score and the binding energies computed at the quantum mechanical level is obviously helpful for identification of oxyresveratrol analogues as a putative anti-inflammatory agent.

Quantitative 1 HNMR spectroscopy for the determination of oxyresveratrol in Artocarpus lacucha heartwood.

INTRODUCTION: Quantitative nuclear magnetic resonance (qNMR) spectroscopy is an analytical method based on the principles of NMR spectroscopy. The main advantages of this method are its simplicity, time efficiency, high accuracy and reproducibility, and it is a non-destructive technique. OBJECTIVE: To evaluate and standardise the quality of Artocarpus lacucha heartwood. A method for quantifying its oxyresveratrol content using qNMR was developed. METHODOLOGY: Proton (1 H)NMR (400 MHz) spectroscopy was used to analyse the methanol-d4 solution of a given amount of crude extract of A. lacucha heartwood using ethyl p-methoxycinnamate (EPMC) as an internal standard. The qNMR methodology was validated in terms of its linearity and range, limit of quantification (LOQ), stability, precision, and accuracy for the determination of the oxyresveratrol content. RESULTS: The qNMR method was validated in terms of its linearity, range, LOQ, accuracy, precision, and stability. The quantitative determination of the oxyresveratrol content in the methanolic crude extract of A. lacucha was found to be 17% based on 1 HNMR analysis, which proved to be a reliable method as the results were comparable to those obtained by high-performance liquid chromatography (HPLC) analysis. CONCLUSIONS: This study validated qNMR spectroscopy as a reliable analytical procedure to determine oxyresveratrol in A. lacucha heartwood. Therefore, this qNMR method can serve as an alternative to the classical HPLC methods for evaluating and standardising the quality of A. lacucha heartwood.

Simultaneous HPLC analysis of crebanine, dicentrine, stephanine and tetrahydropalmatine in Stephania venosa

ABSTRACT Stephania venosa (Blume) Spreng., Menispermaceae, has been traditionally used as tonic drug and treatment of various diseases in South East Asian countries. In order to evaluate the quality and standardization of S. venosa roots, the HPLC method for quantification of the content of major components in S. venosa was developed and validated. The chromatographic separation was performed on a Hypersil BDS C18 column using gradient system of 100 mM ammonium acetate in water and methanol with flow rate 1 ml/min. Detection wavelength was set at 210 nm for tetrahydropalmatine, 280 nm for dicentrine and crebanine, and 270 nm for stephanine. The validated method showed good sensitivity, linearity, precision, and accuracy. The suitable solvent that yielded highest alkaloids contents from the matrix was optimized. S. venosa samples collected from various locations were analyzed. The present study provided comprehensive overview of major components in S. venosa. A remarkable variation in the accumulation of alkaloids in each population and the between individual in the same population could be observed. Our results showed the heterogeneity of S. venosa in Thailand which would need a further study for species delimitations.

Acetylcholinesterase Inhibitory Activity of Alkaloids Isolated from Stephania venosa.

Stephania venosa (Blume) Spreng or "Sa-Bu-Leud" is a Thai medicinal plant used for treatment of cancer and diabetes, and as a blood-tonic and aphrodisiac. This plant .ontains alkaloids as its major components and has been of interest for its acetylcholinesterase (AChE) inhibitory activity. Phytochemical screening - of S. venosa was made using HPLC analysis and showed the chemical variation between the same species from different provenances. Fractionation of .S..venosa extract yielded three alkaloids, namely, dicentrine, crebanine, and tetrahydropalmatine. AChE inhibitory potential of the isolated alkaloids was evaluated using Ellman's AChE inhibition assay. Dicentrine, crebanine, and tetrahydropalmatine inhibited-AChE activity with IC(50) values of 93.5, 86.6, and 168.6 µg/mL, respectively. The AChE inhibitory activity of the tertiary protoberberine alkaloid, tetrahydropalriiatine, was lower than that of the aporphine alkaloids, dicentrine and crebanine, whereas the quaternary protoberberine alkaloid, berberine, showed a higher AChE inhibitory effect than the others.

Efficient synthesis of biologically interesting 3,4-diaryl-substituted succinimides and maleimides: application of iron-catalyzed carbonylations.

A straightforward two-step synthesis of trans-3,4-disubstituted succinimides through a palladium-catalyzed Sonogashira reaction and an iron-catalyzed double carbonylation is described. In situ oxidative dehydrogenation gave the corresponding 3,4-diarylmaleimides. By starting from readily available aryl and heteroaryl halides, a variety of new analogues and derivatives of bioactive 3,4-bisindolylmaleimides are obtained in good yield and selectivity.

Alpha-functionalization of non-activated aliphatic amines: ruthenium-catalyzed alkynylations and alkylations.

Novel catalytic alpha-functionalizations of non-activated aliphatic amines with silylated alkynes are reported. In the presence of the Shvo catalyst alkylations and alkynylations proceed highly selectively to the branched amines.

First iron-catalyzed synthesis of oximes from styrenes.

Aryl-substituted olefins react with t-butyl nitrite and sodium borohydride in the presence of iron(ii)phthalocyanine to give oximes in moderate to high yields.

A general synthetic route to 1-azabicyclo[m.n.0]alkenes via cyclisation based on alpha-sulfinyl carbanions.

The intramolecular nucleophilic addition of alpha-sulfinyl carbanions derived from the corresponding sufinyl lactams afforded 1-azabicyclo[m.n.0]alkenes in good yields.