TY - GEN
T1 - Discovery of novel α-amylase inhibitors as type two diabetes mellitus therapy through fragment-based drug design
AU - Hidayat, Muhammad Fauzi
AU - Ningsih, Eka Gunarti
AU - Alkaff, Ahmad Husein
AU - Tambunan, Usman Sumo Friend
N1 - Funding Information:
This research is financially supported by Hibah Publikasi Internasional Terindeks 9 (PIT 9) Nomor: NKB 0036/UN2.R3.1/HKP.05.00/2019 Research Project of Universitas Indonesia 2019. Also, all of the researchers hereby declare that there is no conflict of interest regarding the manuscript.
Publisher Copyright:
© 2020 Trans Tech Publications Ltd, Switzerland.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Diabetes is one of the top causes of death in the world with 425 million sufferers reported in 2017. About 90% of people with diabetes suffer from Type 2 Diabetes Mellitus (T2DM). Recent studies show that inhibiting the α-amylase enzyme can significantly decrease the postprandial blood glucose levels through blocking carbohydrate hydrolysis. Therefore, it can be a promising strategy for T2DM treatment. This research was aimed to find the new potential inhibitor for the a-amylase from lead-like compounds Molecular Operating Environment (MOE) database through fragmentbased drug design, combining with structure-based pharmacophore design method to obtain new drug candidate for T2DM. There were 653,214 lead-like compounds which were obtained from MOE database and screened based on the Astex Rules of Three along with toxicity filter to gain lead-like fragments. The filtered fragments were docked into the binding site of the a-amylase utilizing MOE 2014.09 software. Potential lead-like fragments were grown to generate 25,600 new ligands by utilizing DataWarrior v5.0.0 software, based on the Lipinski’s Rule of Five and toxicity filter. Molecular docking simulation and pharmacological tests were performed on the ligand libraries to acquire the best ligand, namely BGOJI, which were chosen according to the lowest ΔG binding score, RMSD value < 2, good molecular interaction, ADME/T-test result.
AB - Diabetes is one of the top causes of death in the world with 425 million sufferers reported in 2017. About 90% of people with diabetes suffer from Type 2 Diabetes Mellitus (T2DM). Recent studies show that inhibiting the α-amylase enzyme can significantly decrease the postprandial blood glucose levels through blocking carbohydrate hydrolysis. Therefore, it can be a promising strategy for T2DM treatment. This research was aimed to find the new potential inhibitor for the a-amylase from lead-like compounds Molecular Operating Environment (MOE) database through fragmentbased drug design, combining with structure-based pharmacophore design method to obtain new drug candidate for T2DM. There were 653,214 lead-like compounds which were obtained from MOE database and screened based on the Astex Rules of Three along with toxicity filter to gain lead-like fragments. The filtered fragments were docked into the binding site of the a-amylase utilizing MOE 2014.09 software. Potential lead-like fragments were grown to generate 25,600 new ligands by utilizing DataWarrior v5.0.0 software, based on the Lipinski’s Rule of Five and toxicity filter. Molecular docking simulation and pharmacological tests were performed on the ligand libraries to acquire the best ligand, namely BGOJI, which were chosen according to the lowest ΔG binding score, RMSD value < 2, good molecular interaction, ADME/T-test result.
KW - Fragment-based drug design
KW - In silico
KW - Lead-like compounds
KW - Type 2 diabetes
KW - α-amylase
UR - http://www.scopus.com/inward/record.url?scp=85085185044&partnerID=8YFLogxK
M3 - Conference contribution
AN - SCOPUS:85085185044
SN - 9783035716139
T3 - Key Engineering Materials
SP - 237
EP - 244
BT - Symposium of Materials Science and Chemistry II
A2 - Wahyuningsih, Tutik Dwi
A2 - Roto, Roto
A2 - Siswanta, Dwi
A2 - Adnan, Rohana
A2 - Commeiras, Laurent
A2 - Triyana, Kuwat
A2 - Triyana, Kuwat
A2 - Kartini, Indriana
A2 - Motuzas, Julius
PB - Trans Tech Publications Ltd
T2 - 5th International Conference on Science and Technology, ICST 2019
Y2 - 30 July 2019 through 31 July 2019
ER -
