Identification of potential drug target in malarial disease using molecular docking analysis.

Malaria caused by genus Plasmodium, is a parasite which is the main health issue for humans and about half of the population were suffered. An every year, approximately 1.2-2.7 million people died due to malaria globally. Therefore to prevent the spreading of malaria from the glob novel active drugs with specific activities are necessary. The present study aimed to identify novel drug molecule together with the bioinformatic tools for the development of active malarial drugs. As the search for latest anti malarial compound was developed, this work determined six active blends from various drug databases which possess drug-like characteristics and presents a significant anti malarial actions in in-silico level. Compound ID 300238, 889, 76569, 87324, 45678, and Z185397112are a few of the ligands were got from the Toss lab, Maybridge, Cambridge, Life chem, Bitter, and Examine drug databases and docked against hexokinase 1 protein (PDB: 1CZA) with high throughput practical screening (HTVS) using Glide v6.6. Amid the 6 compounds, compound no: 300238 from Toss lab has the greatest docking score of -9.889 kcal/mol targeting 1CZA protein. The active sites of Hexokinase I of protein were determine by using superimposition of the destination and template structure showed similar structural folds and active sites which were decidedly conserved. The quality of hexokinase I protein was considered to be sterically stable where the protein was prepared by utilizing the software protein preparation execute in the Schrodinger suite. Prepared proteins were evaluated using SAVES and the studies of molecular dynamics of the hexokinase, and the GROMACS were performed for protein-ligand complex. The low HOMO-LUMO energy gaps of the compound verified the greater stability of the molecule. Here, the tested drug candidates have good absorption, distribution, metabolism, and excretion (ADME) properties which were established by using QikProp, version 3.4 of Schrodinger.

Effect of different Agrobacterium rhizogenes strains for in-vitro hairy root induction, total phenolic, flavonoids contents, antibacterial and antioxidant activity of (Cucumis anguria L.).

The present study aimed to investigate the effect of different Agrobacterium rhizogenes on the induction of hairy root of Cucumis anguria and determine its total phenolic, flavonoids contents, antibacterial and antioxidant activity. In this investigation A. rhizogenes strains such as, 15834, 13333, A4, R1200, R1000, LBA9402, R1301 and R1601 are all investigated, were developing hairy root conception in cotyledon and leaf tissue explants. Polymerase chain response (PCR) and the converse transcription-PCR are transgenic clones of hairy roots has been utilized rolA and rolB particular primers. In the middle of the different attention of better regulators the extreme transformation frequency was achieved in (IBA + NAA) cotyledon explant. Transgenic hairy roots increase in MS liquid medium added to with IBA + NAA (2.46 + 1.07) displayed the maximum accumulation of biomass 0.68 g/l dry weight (DW) and 6.52 ± 0.49 g/l fresh weight (FW) were obtained at the 21 days of cotyledon explant. The flavonoid and total phenolic contents were estimated using aluminium chloride method and Folin-Ciocalteu method. The amount of phenolic compounds in Cucumis anguria L non transformed root (124.46 ± 6.13 mg GA/g) was lower than that in the methanol extracts of Cucumis anguria L. hairy roots (160.38 ± 5.0 mg GA/g), being was Cucumis anguria L non transformed root lower (42.93 ± 1.58 mg rutin/g) than that in the concentration of total flavonoids in Cucumis anguria L. hairy root (16.26 ± 1.84 mg rutin/g). Additionally, transgenic hairy roots professionally produced various phenolic and flavonoid composites. The total antimicrobial activity, phenolics, flavonoids content and antioxidant were more in the hairy roots related to non-transformed roots. In our discovery, the A. rhizogenes R1000 is promising candidate for hairy root initiation of C. anguria from cotyledone explants were realized large number of hairy roots compared with leaf explants. The antioxidant potential of methanol extracts of flavonoid and phenolic compounds from the hairy roots have great potential to treat various diseases.

Improvement of the pharmacological activity of menthol via enzymatic ß-anomer-selective glycosylation.

Menthol has a considerable cooling effect, but the use range of menthol is limited because of its extremely low solubility in water and inherent flavor. (-)-Menthol ß-glucoside was determined to be more soluble in water (>27 times) than (-)-menthol α-glucoside; hence, ß-anomer-selective glucosylation of menthol is necessary. The in vitro glycosylation of (-)-menthol by uridine diphosphate glycosyltransferase (BLC) from Bacillus licheniformis generated (-)-menthol ß-glucoside and new (-)-menthol ß-galactoside and (-)-menthol N-acetylglucosamine. The maximum conversion rate of menthol to (-)-menthol ß-D-glucoside by BLC was found to be 58.9%. Importantly, (-)-menthol ß-D-glucoside had a higher cooling effect and no flavor compared with menthol. In addition, (-)-menthol ß-D-glucoside was determined to be a non-sensitizer in a skin allergy test in the human cell line activation test, whereas menthol was a sensitizer.

Accumulation of Charantin and Expression of Triterpenoid Biosynthesis Genes in Bitter Melon (Momordica charantia).

Charantin, a natural cucurbitane type triterpenoid, has been reported to have beneficial pharmacological functions such as anticancer, antidiabetic, and antibacterial activities. However, accumulation of charantin in bitter melon has been little studied. Here, we performed a transcriptome analysis to identify genes involved in the triterpenoid biosynthesis pathway in bitter melon seedlings. A total of 88,703 transcripts with an average length of 898 bp were identified in bitter melon seedlings. On the basis of a functional annotation, we identified 15 candidate genes encoding enzymes related to triterpenoid biosynthesis and analyzed their expression in different organs of mature plants. Most genes were highly expressed in flowers and/or fruit from the ripening stages. An HPLC analysis confirmed that the accumulation of charantin was highest in fruits from the ripening stage, followed by male flowers. The accumulation patterns of charantin coincide with the expression pattern of McSE and McCAS1, indicating that these genes play important roles in charantin biosynthesis in bitter melon. We also investigated optimum light conditions for enhancing charantin biosynthesis in bitter melon and found that red light was the most effective wavelength.

Influence of Indole-3-Acetic Acid and Gibberellic Acid on Phenylpropanoid Accumulation in Common Buckwheat (Fagopyrum esculentum Moench) Sprouts.

We investigated the effects of natural plant hormones, indole-3-acetic (IAA) acid and gibberellic acid (GA), on the growth parameters and production of flavonoids and other phenolic compounds in common buckwheat sprouts. A total of 17 phenolic compounds were identified using liquid chromatography-mass spectrometry (LC-MS) analysis. Among these, seven compounds (4-hydroxybenzoic acid, catechin, chlorogenic acid, caffeic acid, epicatechin, rutin, and quercetin) were quantified by high-performance liquid chromatography (HPLC) after treating the common buckwheat sprouts with different concentrations of the hormones IAA and GA. At a concentration of 0.5 mg/L, both IAA and GA exhibited the highest levels of growth parameters (shoot length, root length, and fresh weight). The HPLC analysis showed that the treatment of sprouts with IAA at concentrations ranging from 0.1 to 1.0 mg/L produced higher or comparable levels of the total phenolic compounds than the control sprout and enhanced the production of rutin. Similarly, the supplementation with 0.1 and 0.5 mg/L GA increased the content of rutin in buckwheat sprouts. Our results suggested that the treatment with optimal concentrations of IAA and GA enhanced the growth parameters and accumulation of flavonoids and other phenolic compounds in buckwheat sprouts.

Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa.

The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors from natural plants, bioassay-guided fractionation of lipophilic n-hexane and chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led to the isolation of 12 compounds (1-12) including murrayafoline-A (1), isomahanine (2), bisisomahanine (3), saropeptate (4), (24 S)-ergost-4-en-3,6-dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), ß-sitosterol (8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)-epiloliolide (12). Their structures were elucidated on the basis of spectroscopic data. Among them, neosarmentol III (11) was isolated from nature for the first time. All the isolated compounds were evaluated for their inhibitory activity against sEH. Among isolated carbazole-type compounds, isomahanine (2) and bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC50 values of 22.5 ± 1.7 and 7.7 ± 1.2 µM, respectively. Moreover, the inhibitory action of 2 and 3 represented mixed-type enzyme inhibition.

Anti-osteoporotic and antioxidant activities of chemical constituents of the aerial parts of Ducrosia ismaelis.

A new pterocarpan glycoside, glycinol-3-O-ß-D-glucopyranoside (1), and a new dihydrochalcone glycoside, ismaeloside A (2), were isolated together with 13 known compounds, including several flavonoids (3-8), lignans (9-11), and phenolic compounds (12-15), from the methanol extract of the aerial parts of Ducrosia ismaelis. The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The anti-osteoporotic and antioxidant activities of the isolated compounds were assessed using tartrate-resistant acid phosphatase (TRAP), oxygen radical absorbance capacity (ORAC), and reducing capacity assays. Compound 15 exhibited a dose-dependent inhibition of osteoclastic TRAP activity with a TRAP value of 86.05±6.55% of the control at a concentration of 10 µM. Compounds 1, 3-5, and 8 showed potent peroxyl radical-scavenging capacities with ORAC values of 22.79±0.90, 25.57±0.49, 20.41±0.63, 26.55±0.42, and 24.83±0.12 µM Trolox equivalents (TE) at 10 µM, respectively. Only compound 9 was able to significantly reduce Cu(I) with 23.44 µM TE at a concentration of 10 µM. All of the aforementioned compounds were isolated for the first time from a Ducrosia species.