Discovery of azaleatin as a potential allosteric inhibitor for dengue NS2B-NS3 protease using in vitro and in silico studies.

The rise in dengue cases in tropical and sub-tropical areas has become a significant health concern. At present, there is no definitive cure for dengue fever, which underscores the importance of identifying potent inhibitors. Dengue NS2B-NS3 protease is the prime drug target due to its vital function for replication. Quercetin, a flavone, has anti-dengue virus properties but is limited by low bioavailability. Previous studies have shown that methoxy substitution in flavones improves bioavailability and metabolic stability. Azaleatin is a derivative of quercetin with a methoxy substitution at the C5 position, however its ability to inhibit dengue is unknown. In this study, azaleatin was investigated for its inhibition against dengue NS2B-NS3 protease using in vitro and in silico techniques. The fluorescence assay was used to determine the IC50 value and inhibition kinetics. The molecular interaction between azaleatin and NS2B-NS3 was studied using CB-Dock2 and AutoDock Vina. The complex's stability was then analysed using GROMACS. Besides, the ADMETlab 2.0 was utilized to predict pharmacokinetic of the azaleatin. Results showed that azaleatin inhibits dengue NS2B-NS3 protease non-competitively with a Ki of 26.82 µg/ml and an IC50 of 38 µg/ml. Molecular docking indicated binding of the azaleatin to the allosteric pocket of NS2B-NS3 with a docking score of -8.2 kcal/mol. Azaleatin was found stable in the pocket along 100 ns, supporting its inhibitory mode. The compound has favourable pharmacokinetic profiles and conformed to Lipinski's Rule of Five. Taken together, azaleatin inhibits NS2B-NS3 protease in a non-competitive mode, suggesting its potential as safer anti-dengue compound.Communicated by Ramaswamy H. Sarma.

Phytochemistry, Bioactivities and Traditional Uses of Michelia × alba.

Michelia × alba (M. alba) is a flowering tree best known for its essential oil, which has long been used as a fragrance ingredient for perfume and cosmetics. In addition, the plant has been used in traditional medicine in Asia and dates back hundreds of years. To date, there is a limited number of publications on the bioactivities of M. alba, which focused on its tyrosinase inhibition, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant activities. Nevertheless, M. alba may have additional unexplored bioactivities associated with its bioactive compounds such as linalool (72.8% in flower oil and 80.1% in leaf oil), α-terpineol (6.04% flower oil), phenylethyl alcohol (2.58% flower oil), ß-pinene (2.39% flower oil), and geraniol (1.23% flower oil). Notably, these compounds have previously been reported to exhibit therapeutic activities such as anti-cancer, anti-inflammation, anti-depression, anti-ulcer, anti-hypertriglyceridemia, and anti-hypertensive activities. In this review paper, we examine and discuss the scientific evidence on the phytochemistry, bioactivities, and traditional uses of M. alba. Here, we report a total of 168 M. alba biological compounds and highlight the therapeutic potential of its key bioactive compounds. This review may provide insights into the therapeutic potential of M. alba and its biologically active components for the prevention and treatment of diseases and management of human health and wellness.

Chemical composition of three Malaysian Horsfieldia essential oils.

This study aims to assess the chemical compositions of the essential oils from three Horsfieldia species namely H. fulva Warb., H. sucosa Warb. and H. superba Warb., which are found in Malaysia. The essential oils were derived from the samples through hydrodistillation which were then characterised by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Based on the findings, the H. fulva, H. sucosa and H. superba essential oils represented 98.2%, 98.7% and 98.5% of the total oils, respectively. The major component of H. fulva oil was identified to be germacrene D (20.8%), H. sucosa oil mainly contained α-cadinol (17.5%), whereas H. superba oil was rich in δ-cadinene (18.2%). To the best of our knowledge, this is the first study of the composition of the essential oils from these selected Horsfieldia species.

In silico approach for Post-SELEX DNA aptamers: A mini-review.

Aptamers are short oligonucleotides that possess high specificity and affinity against their target. Generated via Systematic Evolution of Ligands by Exponential Enrichment, (SELEX) in vitro, they were screened and enriched. This review covering the study utilizing bioinformatics tools to analyze primary sequence, secondary and tertiary structure prediction, as well as docking simulation for various aptamers and their ligand interaction. Literature was pooled from Web of Science (WoS) and Scopus databases until December 18, 2020 using specific search string related to DNA aptamers, in silico, structure prediction, and docking simulation. Out of 330 published articles, 38 articles were assessed in the analysis based on the predefined inclusion and exclusion criteria. It was found that Mfold and RNA Composer web server is the most popular tool in secondary and tertiary structure prediction of DNA aptamers, respectively. Meanwhile, in docking simulation, ZDOCK and AutoDock are preferred to analyze binding interaction in the aptamer-ligand complex. This review reports a brief framework of recent developments of in silico approaches that provide predictive structural information of ssDNA aptamer.

Composition of the essential oils of three Malaysian Xylopia species (Annonaceae).

The rich and diversified Malaysian flora represents an excellent resource of new chemical structures with biological activities. The genus Xylopia L. includes aromatic plants that have both nutritional and medicinal uses. This study aims to contribute with information about the volatile components of three Xylopia species essential oils: Xylopia frutescens, Xylopia ferruginea, and Xylopia magna. In this study, essential oils were extracted from the leaves by a hydrodistillation process. The identification of the essential oil components was performed by gas chromatography (GC-FID) and gas chromatography-coupled mass spectrometry (GC-MS). The major components of the essential oils from X. frutescens were bicyclogermacrene (22.8%), germacrene D (14.2%), elemol (12.8%), and guaiol (12.8%), whereas components of the essential oils from X. magna were germacrene D (35.9%), bicyclogermacrene (22.8%), and spathulenol (11.1%). The X. ferruginea oil was dominated by bicyclogermacrene (23.6%), elemol (13.7%), guaiol (13.4%), and germacrene D (12.3%).

Antioxidant activities and tyrosinase inhibition effects of Phaleria macrocarpa extracts.

BACKGROUND: The ethyl acetate and chloroform extracts of stems, leaves and fruits of Phaleria macrocarpa were screened for their antioxidant capacity and tyrosinase inhibition properties. MATERIAL AND METHOD: The total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric-ion reducing power (FRAP) were used to evaluate their antioxidant capacity. Tyrosinase inhibition effect was measured using mushroom tyrosinase inhibition assay. RESULT: Ethyl acetate extract of P. macrocarpa's stem exhibited highest total phenolic content, DPPH free radical scavenging and ferric reducing power. Meanwhile, chloroform extracts of leaves and fruits demonstrated potent anti-tyrosinase activities as compared to a well-known tyrosinase inhibitor, kojic acid. CONCLUSION: Since chloroform extracts of leaves and fruits have low antioxidant capacities, the tyrosinase inhibition effect observed are antioxidant independent. This study suggests direct tyrosinase inhibition by chloroform extracts of Phaleria macrocarpa.