@article {640, title = {Indonesian Herbal SGLT2 Inhibitor Discovery through Pharmacophore-Based Virtual Screening}, journal = {Pharmacognosy Journal}, volume = {10}, year = {2018}, month = {June 2018}, pages = {803-807}, type = {Original Article}, chapter = {803}, abstract = {

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitor had been evaluated in clinical trials as the basic strategy of hyperglycemia handling in diabetes. However, because of SGLT2 inhibitors is the new class of oral antidiabetic, it is rare to be found in Indonesia, and it is costly. This study was intended to find compounds from Indonesian herbal database that show capability to be used as SGLT2 inhibitors through a pharmacophore-based virtual screening approach. Methods: The SGLT2 inhibitor pharmacophore models were made from 10 training sets of SGLT2 ligand inhibitors using the Ligand Scout 4.1.5. Ten pharmacophore models which had been made were validated using test set and decoy set methods to know how the performance of pharmacophore model worked. Virtual screening were then applied to the best pharmacophore model. Results: The model-1 pharmacophore was the best model, with values of 0.9080, EF1\% = 56.5, EF5\% = 56.5 and AUC100\% = 0.87 which served as model for virtual screening. Model-1 consisted of one hydrophobic interaction, one aromatic ring, four hydrogen bond donors and five hydrogen bond acceptors. Virtual screening showed three compounds (Hits) with best pharmacophore fit scores according to model-1 among 1377 compounds, they were vitexin = 113.62; cucumerin A = 112.62; and cucumerin B = 113.51. Conclusion: These results showed that vitexin, cucumerin A, and cucumerin B potentially have activity as an SGLT2 inhibitor.

}, keywords = {Diabetes, Pharmacophore, SGLT2 Inhibitor, Virtual Screening}, doi = {10.5530/pj.2018.4.136}, url = {http://fulltxt.org/article/674}, author = {Rezwendy R and Rezi Riadhi Syahdi and Arry Yanuar} } @article {620, title = {Pharmacophore Modelling of Brassicaceae Members as Potent HIF (Hypoxia Inducible Factor) Inhibitors Involved in Cancer Angiogenesis}, journal = {Pharmacognosy Journal}, volume = {10}, year = {2018}, month = {May 2018}, pages = {798-802}, type = {Original Article}, chapter = {798}, abstract = {

Angiogenesis is considered as an essential pathological feature of cancer due to its interplay between cancer and other diseases. Natural products found to act as antiangiogenic agents that mediate the angiogenic switch between pro and anti angiogenic factors. Among the different targets, HIF is an important and critical factor that stands as a key mediator between angiogenesis, inflammation and cancer. In our study different phytochemicals of Brassicaceae were analysed for their drug like properties and mapped for pharmacophore development. The developed pharmacophore was virtually screened and further subjected to Lipinski and ADMET filters. The molecular interaction studies of the 10 retrieved compounds were studied by binding with HIF. Among the compounds 1stdrug like molecule HTS 0115 (C15H21BrN2O3) was found to have best docked score and its interaction was further validated using dynamics simulation. The compound found to share the pharmacophoric features with progoitrin a biochemical form of glucosinolate with reported anticancer and anti thyroid activities. Thus the drug like compound HTS 0115 can be further optimised as a putative HIF inhibitor in tumor angiogenesis.

}, keywords = {Angiogenesis, Brassicaceae, HIF, Molecular docking, Pharmacophore, Simulation}, doi = {10.5530/pj.2018.4.135}, url = {http://fulltxt.org/article/673}, author = {Jeyavel Renukadevi and Ganesan Nandhinidevi and Muthiah Bavanilatha and Hemanath Tharani and Rajarajan Sathiyabama and Subramani Vasumathi} }