Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava.
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.
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman; Department of Chemistry, Federal Urdu University of Arts, Science and Technolgy, Karachi, Pakistan.
Muhammad Adil
MA
Raees
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman. Electronic address: hussainchem3@gmail.com.
Hidayat
H
Hussain
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman.
Ahmed
A
Al-Rawahi
Martin-Luther Universität Halle-Wittenberg, Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle, Germany.
René
R
Csuk
Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
Syed Aun
SA
Muhammad
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman.
Husain Yar
HY
Khan
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman.
Najeeb Ur
NU
Rehman
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman; Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, Birkat Al-Mouz, Nizwa 616, Oman.
Ghulam
G
Abbas
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman.
Mohammed Abdullah
MA
Al-Broumi
Department of Chemistry and Polymer Science, University of Stellenbosch, P/Bag X1, Matieland 7602, South Africa.
Ivan R
IR
Green
DARIS Centre for Scientific Research and Technology Development, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman.
Ali
A
Elyassi
Department of Chemistry, Federal Urdu University of Arts, Science and Technolgy, Karachi, Pakistan.
Talat
T
Mahmood
UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman. Electronic address: aharrasi@unizwa.edu.om.
Ahmed
A
Al-Harrasi
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011278:Pregnanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D011278:Pregnanes; C574437:pregnane glycoside
Anti-proliferative activity; Desmidorchis flava; Docking study; Natural product; Pregnane glycoside