TY - JOUR
T1 - Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease
AU - Alomari, Munther
AU - Taha, Muhammad
AU - Imran, Syahrul
AU - Jamil, Waqas
AU - Selvaraj, Manikandan
AU - Uddin, Nizam
AU - Rahim, Fazal
N1 - Funding Information:
The authors would like to Knowledge Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, for providing excellent lab facilities for research.
Publisher Copyright:
© 2019 Elsevier Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/11
Y1 - 2019/11
N2 - Hybrid bis-coumarin derivatives 1–18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure–activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.
AB - Hybrid bis-coumarin derivatives 1–18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure–activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.
KW - Biscoumarin
KW - Molecular docking
KW - Synthesis
KW - Thiadiazole
KW - Urease inhibition
UR - https://www.scopus.com/pages/publications/85071689548
U2 - 10.1016/j.bioorg.2019.103235
DO - 10.1016/j.bioorg.2019.103235
M3 - Article
C2 - 31494327
AN - SCOPUS:85071689548
SN - 0045-2068
VL - 92
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 103235
ER -