A bioinformatic approach to establish P38? MAPK inhibitory mechanism of selected natural products in psoriasis-Supplementary data

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38? mitogen-activated protein kinases (P38? MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38? MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38? MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (?9.00 and ?8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action.

A bioinformatic approach to establish P38? MAPK inhibitory mechanism of selected natural products in psoriasis

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38? mitogen-activated protein kinases (P38? MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38? MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38? MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (?9.00 and ?8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action.

Modeling and Molecular Docking Studies on Alangium salvifolium (Alanginaceae) as a Target for Anti-oxidant Enzyme

Objectives: The present studies pursue at retrieve and draws the active phytocompounds structure of Alangium salvifolium and assessing its simulation anti-oxidant enzyme activities. Methods: Retrieve/draws of the compounds were carried out using chem.-sketch software. The 3-D structures of the Phytocompounds were visualized based upon the UV, NMR spectral data along with their energy simulation studies. The antioxidant and enzyme simulation activity were evaluated in-silico using the ACD labs,PyRx, RASMOL,PYMOL,Aragslab and Discovery 3.1 studio. Key Findings: Phytochemicals structure drawing of A. salvifolium resulted in the structured and recognition of four phytochemicals. The plant phytochemicals showed significant anti-oxidant enzymes activity enhancer and ROS eliminator through binding to its metal domain receptor. Conclusion: Phytochemicals were drawing from A. salvifolium. To the best of our knowledge, among these phytochemicals, were studied anti-oxidant enzymes metals binding domain to increase the ROS scavenging activity for the foremost time from mimic with molecular docking. Moreover, study of phytochemicals simulation was for the first time from this plant. The plant revealed auspicious increase the antioxidant activities virtual screening. This gives thinking to some of its pharmacological properties and suggests additional antioxidant effects, for as a scavenger as well as anti-oxidant enzyme stimulator, which have not been reported yet.

Antibacterial potential of Caesalpinia bonducella extracts and their isolated phytoconstituents: in vitro and in silico analysis

The antimicrobial activity of Caesalpinia bonducella extracts such as CLC, CLE, CSC, and CSE and thephytoconstituents such as β-Sitosterol (LC3) isolated from CLC and methyl (4E)-5-{2-[(1E)-buta-1,3-dien-1-yl]-4,6-dihydroxyphenyl} pent-4-enoate (SC2) isolated from CSC were evaluated on gram-positive and gram-negativebacteria. The extracts and isolated compounds were found to have moderate-to-significant bacterial inhibition. Thesignificant activity was observed in the inhibition of Pseudomonas aeruginosa by CLC extract (16.10 ± 1.10 mm),whereas the isolated phytocomponent SC2 showed the highest inhibition (16.50 ± 0.58 mm). Further, the isolatedcompounds were subjected to molecular docking studies of the bacterial DNA Gyrase. The in silico study showedthe docking energy of −6.4 and three hydrogen bonding. This in vitro and in silico analysis of extracts and isolatedphytocomponents of C. bonducella helps to understand and evaluate the therapeutic efficacy to cure infectiousdiseases and also supports the traditional medicinal claim as an antibiotic.

Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it's in silico docking study against CDK-10

ABSTRACT Roccella montagnei Bél. belongs to lichen family Roccelleceae growing luxuriantly along the coastal regions of India. As Roccella has been shown to be bioactive, we prepared methanolic extract and assessed its anticancer potential. The methanolic extract showed significant in vitro cytotoxic activity against four human cancer cell lines such as colon (DLD-1, SW-620), breast (MCF-7), head and neck (FaDu). This prompted us to isolate bioactive compounds through column chromatography. Two compounds roccellic acid and everninic acid have been isolated, out of which everninic acid is reported for the first time. Both the compounds have been tested for in vitro cytotoxic activity in which roccellic acid showed strong anticancer activity as compared to the everninic acid. Cyclin Dependent Kinase (CDK-10) contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases therefore constitute biomarkers of proliferation and attractive pharmacological targets for development of anticancer therapeutics. Therefore both the isolated compounds were tested for in silico molecular docking study against Cyclin Dependent Kinase isomer enzyme to support the cytotoxic activity.

Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.