35756-54-8Relevant articles and documents
Synthesis and antiproliferative activity of hybrid thiosemicarbazone derivatives bearing coumarin and d-galactose moieties with EGFR inhibitory activity and molecular docking study
Toan, Vu Ngoc,Thanh, Nguyen Dinh
, p. 1868 - 1885 (2021/08/23)
A series of substituted N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)thiosemicarbazones 5a–5j of substituted 3-acetylcoumarins were synthesized with yields of 45–68%. All synthesized thiosemicarbazones were evaluated for cytotoxic activity against several cancer cell lines, such as human breast adenocarcinoma cells MCF7, human liver cancer cells HepG2, human cervical cancer cells HeLa, human melanoma cancer cells SK-Mel-2, and human lung cancer cells LU-1 by using the standard MTT assay. The IC50 values for these cancer cell lines were 1.28–11.81 μM (for MCF-7), 1.53–22.12 μM (for HepG2), 1.43–48.16 μM (for HeLa), 1.82–14.62 μM (for SK-Mel-2), and 1.74–14.62 μM (for LU-1). Most of the compounds were noncytotoxic against human WI-38 normal cell line (IC50 > 16.9 μM). The antiproliferative mechanisms were studied via EGFR inhibition and molecular docking. Docking studies revealed that there are strong interactions between a typical compound with the receptor of the EGFR tyrosine kinase domain with Erlotinib. [Figure not available: see fulltext.]
Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties
Choi, Wonbeen,Villegas, Valente,Istre, Hannah,Heppler, Ben,Gonzalez, Niki,Brusman, Nicole,Snider, Lindsey,Hogle, Emily,Tucker, Janelle,O?ate, Alma,O?ate, Sandra,Ma, Lili,Paula, Stefan
, p. 686 - 695 (2019/03/05)
Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol. Varying systematically the number and positions of the hydroxyl groups at the two phenyl rings, we derived structure-activity relationships based on experimentally determined XO inhibition data. Molecular docking suggested that critical enzyme/inhibitor interactions involved π-π interactions between the phenolic inhibitor ring and Tyr914, hydrogen bonds between inhibitor hydroxyl groups and Glu802, and hydrophobic interactions between the CAPE phenyl ring and non-polar residues located at the entrance of the binding site. To effectively scavenge the stable radical DPPH, two hydroxyl groups in 1,2- or 1,4-position at the phenyl ring were required. Among all compounds tested, E-phenyl 3-(3,4-dihydroxyphenyl)acrylate, a CAPE analog without the ethyl tether, showed the most promising properties.
Coumarin derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies
Singla, Shaffali,Piplani, Poonam
, p. 4587 - 4599 (2016/09/13)
A series of novel hybrids has been synthesized by linking coumarin moiety through an appropriate spacer to various substituted heterocyclic amines and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of cognitive dysfunction caused by increased hydrolysis of acetylcholine and scopolamine induced oxidative stress. Anti-amnesic activity of the compounds was evaluated using Morris water maze model at a dose of 1?mg/kg with reference to the standard, donepezil. Biochemical estimation of oxidative stress markers (lipid peroxidation, superoxide dismutase, and plasma nitrite) was carried out to assess the antioxidant potential of the synthesized molecules. Among all the synthesized compounds (15a–i, 16a–d, 17a–b), compound 15a [4-[3-(4-phenylpiperazin-1-yl)propoxy]-2H-chromen-2-one] displayed significant antiamnesic activity, AChE inhibitory activity (IC50?=?2.42?μM) and antioxidant activity in comparison to donepezil (IC50?=?1.82?μM). Molecular docking study of 15a indicated that it interacts with all the crucial amino acids present at the CAS, mid-gorge and PAS of TcAChE resulting in increased inhibition of AChE enzyme.
