Citation
Kurt, Belma Zengin, et al. "Synthesis, Biological Activity and Multiscale Molecular Modeling Studies of Bis-coumarins as Selective Carbonic Anhydrase IX and XII Inhibitors With Effective Cytotoxicity Against Hepatocellular Carcinoma." Bioorganic Chemistry, vol. 87, 2019, pp. 838-850.
Kurt BZ, Dag A, Doğan B, et al. Synthesis, biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma. Bioorg Chem. 2019;87:838-850.
Kurt, B. Z., Dag, A., Doğan, B., Durdagi, S., Angeli, A., Nocentini, A., Supuran, C. T., & Sonmez, F. (2019). Synthesis, biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma. Bioorganic Chemistry, 87, 838-850. https://doi.org/10.1016/j.bioorg.2019.03.003
Kurt BZ, et al. Synthesis, Biological Activity and Multiscale Molecular Modeling Studies of Bis-coumarins as Selective Carbonic Anhydrase IX and XII Inhibitors With Effective Cytotoxicity Against Hepatocellular Carcinoma. Bioorg Chem. 2019;87:838-850. PubMed PMID: 31003041.
TY - JOUR
T1 - Synthesis, biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma.
AU - Kurt,Belma Zengin,
AU - Dag,Aydan,
AU - Doğan,Berna,
AU - Durdagi,Serdar,
AU - Angeli,Andrea,
AU - Nocentini,Alessio,
AU - Supuran,Claudiu T,
AU - Sonmez,Fatih,
Y1 - 2019/03/07/
PY - 2019/02/02/received
PY - 2019/02/14/revised
PY - 2019/03/02/accepted
PY - 2019/4/20/pubmed
PY - 2020/9/23/medline
PY - 2019/4/20/entrez
KW - Carbonic anhydrase
KW - Coumarin
KW - Cytotoxicity
KW - Molecular Dynamics (MD) Simulations
KW - Molecular docking
SP - 838
EP - 850
JF - Bioorganic chemistry
JO - Bioorg Chem
VL - 87
N2 - A series of novel bis-coumarin derivatives containing triazole moiety as a linker between the alkyl chains was synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms I, II, IX and XII were evaluated. In addition, cytotoxic effects of the synthesized compounds on renal adenocarcinoma (769P), hepatocellular carcinoma (HepG2) and breast adeno carcinoma (MDA-MB-231) cell lines were examined. While the hCA I and II isoforms were inhibited in the micromolar range, the tumor-associated isoform hCA IX and XII were inhibited in the high nanomolar range. 4-methyl-7-((1-(12-((2-oxo-2H-chromen-7-yl)oxy)dodecyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5p) showed the strongest inhibitory activity against hCA IX with the Ki of 144.6 nM and 4-methyl-7-((1-(10-((2-oxo-2H-chromen-7-yl)oxy)decyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5n) exhibited the highest hCA XII inhibition with the Ki of 71.5 nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modelling approaches were applied. Low energy docking poses of studied molecules at the binding sites of targets have been predicted. In addition, electrostatic potential surfaces (ESP) for binding sites were also generated to understand interactions between proteins and active ligands.
SN - 1090-2120
UR - https://www.unboundmedicine.com/medline/citation/31003041/Synthesis_biological_activity_and_multiscale_molecular_modeling_studies_of_bis_coumarins_as_selective_carbonic_anhydrase_IX_and_XII_inhibitors_with_effective_cytotoxicity_against_hepatocellular_carcinoma_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(19)30171-3
DB - PRIME
DP - Unbound Medicine
ER -
