TY - JOUR
T1 - Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives
AU - Taha, Muhammad
AU - Tariq Javid, Muhammad
AU - Imran, Syahrul
AU - Selvaraj, Manikandan
AU - Chigurupati, Sridevi
AU - Ullah, Hayat
AU - Rahim, Fazal
AU - Khan, Fahad
AU - Islam Mohammad, Jahidul
AU - Mohammed Khan, Khalid
N1 - Funding Information:
Authors would like to acknowledge the Ministry of Higher Education (MOHE) for financial support under the Fundamental Research Grant Scheme (FRGS) with sponsorship reference numbers FRGS/1/2016/STG01/UiTM/02/2, Universiti Teknologi MARA for the financial support under LESTARI grant 600-RMI/DANA /5/3/ lestari (54/2013), Ministry of Higher Education Pakistan for financial support under the National Research Program for Universities, project number 5721, Ministry of Higher Education, Malaysia (MOHE) for funding the computational part (Software and Workstation) through the ??TRGS? (grant no. 600-RMI/TRGS 5/3 (1/2014)-3) and AIMST University, Malaysia for providing the facilities for this project.
Publisher Copyright:
© 2017 Elsevier Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/10
Y1 - 2017/10
N2 - α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1−30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002 ± 0.60 and 42.31 ± 0.17 μM which is many folds better than standard acarbose having IC50 value 53.02 ± 0.12 μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.
AB - α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1−30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002 ± 0.60 and 42.31 ± 0.17 μM which is many folds better than standard acarbose having IC50 value 53.02 ± 0.12 μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.
KW - SAR
KW - Synthesis
KW - Thiadiazole quinoline
KW - α-Amylase inhibitory potential
UR - http://www.scopus.com/inward/record.url?scp=85027553854&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2017.08.003
DO - 10.1016/j.bioorg.2017.08.003
M3 - Article
C2 - 28826047
AN - SCOPUS:85027553854
SN - 0045-2068
VL - 74
SP - 179
EP - 186
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -
