Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava
| Autor: | Ahmed Al-Rawahi, Ivan R. Green, Ali Elyassi, Ghulam Abbas, Talat Mahmood, René Csuk, Najeeb Ur Rehman, Ahmed Al-Harrasi, Mohammed Al-Broumi, Muhammad Adil Raees, Husain Yar Khan, Hidayat Hussain, Syed Aun Muhammad |
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| Rok vydání: | 2016 |
| Předmět: |
Cell Survival
Stereochemistry 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Structure–activity relationship Glycosides Molecular Biology Cell Proliferation chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Pregnane Glycoside Pregnanes Ligand (biochemistry) Antineoplastic Agents Phytogenic Small molecule 0104 chemical sciences Apocynaceae Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) Cancer cell Drug Screening Assays Antitumor Growth inhibition |
| Zdroj: | Bioorganic Chemistry. 67:95-104 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2016.05.008 |
| Popis: | Two new pregnane glycosides named desmiflavasides C (1) and D (2) were isolated from the sap of Desmidorchis flava (N.E.Br.) Meve & Liede and have had their structures confirmed from 1D and 2D NMR spectroscopic techniques and mass spectrometry (ESIMS). Further, the effects of desmiflavasides C (1) and D (2) on the proliferation of breast and ovarian cancer cells as well as normal breast epithelial cells in culture were examined. Interestingly, desmiflavasides C (1) and D (2) were able to cause a substantial decline in the viability of cancer cells in a concentration-dependent manner. Moreover, treatment of normal cells with compound 2 resulted in no significant growth inhibition, indicating that its cytotoxicity was selective towards cancer cells. Furthermore, the activity of compound 2 against cancer as well as normal epithelial cells was found to be similar to that of a previously reported pregnane glycoside, nizwaside (3). Molecular docking studies of desmiflavasides C (1) and D (2) and nizwaside (3) were carried out to ascertain if it was possible to predict any important binding orientations required of small molecule drug candidates with suggested protein target molecules for the purposes of being able to predict the affinity and activity to an acceptable degree by such compounds. Desmiflavaside D (2) showed a relatively good binding affinity (-22.4449kcal/mol) as compared to the other two compounds viz., nizwaside (3) (-20.0319kcal/mol), and desmiflavaside C (1) (-19.4042kcal/mol). Docking results of the three pregnane glycosides viz., 1-3 revealed that these ligand molecules can accurately interact with the target protein. |
| Databáze: | OpenAIRE |
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