In silico approach towards the identification of potential inhibitors from Curcuma amada Roxb against H. pylori: ADMET screening and molecular docking studies.

Introduction: The present study attempts to identify potential targets of H. pylori for novel inhibitors from therapeutic herb, mango ginger (Curcuma amada Roxb.). Methods: Crystal structure of all the selected drug targets obtained from Protein Data Bank (PDB) were subjected to molecular docking against a total of 130 compounds (found to have biological activity against H. pylori ) were retrieved from public databases. Compounds with good binding affinity were selected for Prime MM-GBSA rescoring and molecular dynamics (MD) simulation. Final list of compounds were taken for ADMET predictions. Results: Based on binding affinity denoted by glide score and ligand efficiency, mango ginger compounds were found selective to shikimate kinase and type II dehydroquinase through hydrogen bonding and salt bridge interactions. Stability of the interactions and free energy calculations by Prime MM-GBSA results confirmed the affinity of mango ginger compounds towards both shikimate kinase and type II dehydroquinase. From the above results, 15 compounds were calculated for ADMET parameters, Lipinski's rule of five, and the results were found promising without any limitations. MD simulations identified gentisic acid as hit compound for shikimate kinase of H. pylori. Conclusion: Current study could identify the in silico potential of mango ginger compounds against shikimate kinase and type II dehydroquinase targets for H. pylori infections and are suitable for in vitro and in vivo evaluation.

In silico evaluation of drugs used in treatment of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a chronic T cell-mediated, immunological, mucocutaneous disease with a number of genes and inflammatory mediators implicated in its pathogenesis. Heart shock protein 70 and the proinflammatory mediator TNFα have been predominantly involved in the etiopathogenesis of oral lichen planus. METHODS: In this study, the action of 27 commonly used drugs for treating OLP at HSP70 and TNFα were evaluated by molecular docking using Maestro Schrodinger version 10.1. X-ray crystallographic structures of the target proteins, that is, Heat Shock Protein 70 (PDB Code: 6FDT) and tumor necrosis factor alpha-1 (PDB Code: 1TNF) were obtained from Protein Data Bank (PDB). The structures of the ligands (27 drugs) were obtained from PubChem in.sdf format. Using Ligprep, pre-processing of the ligands was done. Extra-precision docking was performed with the prepared protein and the ligands. RESULTS: With respect to HSP70, the highest dock score (-4.768) and glide score (-4.818) were seen with hydroxychloroquine (HCQ), followed by epigallocatechin gallate (green tea), methotrexate, and curcumin. The highest dock (-9.525) and glide score (-9.584) in TNFα were seen in with epigallocatechin gallate, followed by HCQ, dapsone, and methotrexate. CONCLUSION: The results of the study tend to explain the clinical use of HCQ in recalcitrant and severe cases, as well as the anti-inflammatory property of epigallocatechin gallate. The results of the study open ventures for exploring the in silico behavior of drugs for effective pathological management.

A Case Report on Varenicline Induced Delirium in an Alcohol and Nicotine Dependent Patient.

Varenicline is a smoking cessation agent. Varenicline acts as a partial agonist of α4ß2 neuronal nicotinic acetylcholine receptor and prevents nicotine binding to the same. It also causes dopamine (DA) stimulation that decreases craving and symptoms of dependence. A 40-year-old male diagnosed with alcohol and nicotine dependence syndrome was treated with 1 mg of varenicline for 3 days. Patient developed episodes of transient delirium within 15-30 min after administration of varenicline. Patient was disoriented and did not respond relevantly. Patient would have disorientation and would respond irrelevantly and was unable to recall the event completely. There were no features suggestive of seizures. The episodes resolved after the medication was stopped. Varenicline, with its partial agonistic effect on nicotinergic receptors, stimulates the release of multiple neurotransmitters including DA. DA dysregulation is probably responsible for the development of neuropsychiatric adverse reactions due to varenicline. This is the first case report to the best of our knowledge reporting varenicline induced dilirium. In this case, the adverse event was found in an alcohol and nicotine dependent patient undergoing treatment. It is essential to monitor uncommon adverse effects as this can cause significant morbidity.

Inhibition of CCl4-induced liver fibrosis by Piper longum Linn.?

This study was carried out to evaluate the antifibrotic effect of ethanol extract of the fruits of Indian herb Piper longum Linn. Liver fibrosis was induced in rats by CCl(4) administration. The extent of liver fibrosis was assessed by measuring the level of liver hydroxy proline (HP) and serum enzyme levels. Following CCl(4) administration HP was significantly increased and serum enzyme levels were elevated. Treatment with the ethanol extract of Piper longum Linn. reduced the HP and also the serum enzymes. The liver weight that increased following CCl(4) administration due to the deposition of collagen was reduced by the ethanol extract. Hence, it is concluded that this extract inhibits liver fibrosis induced by CCl(4).