Novel Aglycones of Steroidal Glycoalkaloids as Potent Tyrosine Kinase Inhibitors: Role in VEGF and EGF Receptors Targeted Angiogenesis

摘要: Receptor tyrosine kinases (RTKs) are crucial targets in the pathway of angiogenesis and currently used antiangiogenic drugs have limited efficiency with associated toxicity. In our continuous search for new potent multitarget anti-angiogenic lead compounds, we conducted in-silico interaction inhibition studies selected aglycones steroidal glycoalkaloids (GAs) drugs, against EGFR, VEGFR-1, VEGFR-2 using AutoDock Tools 4.0 other online bioinformatics softwares. The docking results been interpreted terms binding energies (kcal/mol) constant ( M). study, [solanidine (solanid-5-en-3 -ol), solasodine (Solasod-5-en-3 -ol) tomatidine (5 -Tomatidan-3 -ol)] gave promising comparable (Gefitinib, Lapatinib, Axitinib Motasenib). All test expressed significant RTKs under but emerged as a most multi-target inhibitor RTKs. was observed almost 2-folds less compared to Gefitinib targeting EGFR 5-folds Axitinib, standard drug VEGFR-2. Moreover, these fulfilled likeliness properties, when analyzed by Lipinski’s Rule Five. addition this, toxicity remarkably showed no mutagenecity tumorigenecity drugs. Our first time report that novel GAs may be compounds development effective least or addition, wet lab experiments underway support