Ligand Based-Pharmacophore Modeling and Extended Bi oactivity Prediction for Salinosporamide A, B and C from Marine Actino mycetes Salinispora tropica

• Published in: Combinatorial chemistry & high throughput screening Vol. 20; no. 1; p. 3
• Main Authors: Dineshkumar, Kesavan, Vasudevan, Aparna, Hopper, Waheeta
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2017
• Subjects: Actinobacteria - chemistry; Actinobacteria - metabolism; Aminopeptidases - metabolism; Drug Discovery; Humans; Lactams - chemistry; Lactams - metabolism; Lactams - pharmacology; Lactones - chemistry; Lactones - metabolism; Lactones - pharmacology; Ligands; Metalloendopeptidases - metabolism; Molecular Docking Simulation; Protein Binding; Pyrroles - chemistry; Pyrroles - metabolism; Pyrroles - pharmacology; Receptors, Glucocorticoid - metabolism; ligand based-pharmacophore; Salinispora sp; salinosporamides; binding energy prediction; glide docking; bioactive target identification
• ISSN: 1875-5402
• DOI: 10.2174/1386207319666161215154128

Actinomycetes produce structurally unique secondary metabolites with pharmaceutically essential bioactivities. Salinispora, an obligate marine actinomycete, produces structurally varied and unique secondary metabolites. There is plenty of scope for development of drugs from the novel compounds isolated from Salinispora. Anticancer, antibacterial and anti-protozoa activities have been shown for Salinosporamides A, B and C, the secondary metabolites identified from Salinispora, which make them interesting subjects for further extended biological activity prediction.
An in silico ligand based-pharmacophore approach was used for the prediction of extended biological targets for salinosporamide A, B and C. Pharmacophore models of salinosporamide A, B and C were generated individually and screened against known drug databases. The drugs with best fitness score were shortlisted, and their respective targets pertaining to their bioactivity were retrieved. The predicted biological drug targets were docked with salinosporamide A, B and C for validation.
The glucocorticoid receptor and methionine aminopeptidase 2 showed good docking score and binding energy with salinosporamide A, B and C. Molecular dynamics studies of the protein-ligand complexes showed stable interactions suggesting that the predicted new targets for salinosporamides might be promising.
The glucocorticoid receptor and methionine aminopeptidase 2 could be possible new drug targets of bioactivity of salinosporamides. These proteins could be the druggable targets for antiinflammatory and anticancer activity of salinosporamides.