40204-26-0Relevant articles and documents
Rational Design and Synthesis of Methyl-β- d -galactomalonyl Phenyl Esters as Potent Galectin-8 N Antagonists
Patel, Brijesh,Kishor, Chandan,Houston, Todd. A.,Shatz-Azoulay, Hadas,Zick, Yehiel,Vinik, Yaron,Blanchard, Helen
supporting information, p. 11573 - 11584 (2020/12/02)
Galectin-8 is a β-galactoside-recognizing protein having an important role in the regulation of bone remodeling and cancer progression and metastasis. Methyl β-d-galactopyranoside malonyl aromatic esters have been designed to target and engage with particular amino acid residues of the galectin-8N extended carbohydrate-binding site. The chemically synthesized compounds had in vitro binding affinity toward galectin-8N in the range of 5-33 μM, as evaluated by isothermal titration calorimetry. This affinity directly correlated with the compounds' ability to inhibit galectin-8-induced expression of chemokines and proinflammatory cytokines in the SUM159 breast cancer cell line. X-ray crystallographic structure determination revealed that these monosaccharide-based compounds bind galectin-8N by engaging its unique arginine (Arg59) and simultaneously cross-linking to another arginine (Arg45) located across the carbohydrate-binding site. This structure-based drug design approach has led to the discovery of novel monosaccharide galactose-based antagonists, with the strongest-binding compound (Kd 5.72 μM) holding 7-fold tighter than the disaccharide lactose.
Design and synthesis of Coenzyme A analogues as Aurora kinase A inhibitors: An exploration of the roles of the pyrophosphate and pantetheine moieties
Bellany, Fiona,Tsuchiya, Yugo,Tran, Trang M.,Chan, A.W. Edith,Allan, Helen,Gout, Ivan,Tabor, Alethea B.
supporting information, (2020/09/16)
Coenzyme A (CoA) is a highly selective inhibitor of the mitotic regulatory enzyme Aurora A kinase, with a novel mode of action. Herein we report the design and synthesis of analogues of CoA as inhibitors of Aurora A kinase. We have designed and synthesised modified CoA structures as potential inhibitors, combining dicarbonyl mimics of the pyrophosphate group with a conserved adenosine headgroup and different length pantetheine-based tail groups. An analogue with a -SH group at the end of the pantotheinate tail showed the best IC50, probably due to the formation of a covalent bond with Aurora A kinase Cys290.
Design, synthesis and biological screening of N-(substituted pyridine-2-yl)-N-(quinoline-2-yl) malonamide as novel anti-HIV-I agents
Kashid, Arun Maruti,Dhawale, Shasbikant
, p. 870 - 879 (2019/05/21)
A novel series of N1-(substiruted pyridine-2-yl)-N3-(quinoline-2-yl) malonamide derivatives (AK1-AK24) has been rationally designed, synthesized and biologically screened for in vitro anti HIV activity by using reverse transcriptase assay kit (Roche). Out of the synthesized compounds, compound AK1, AK2 and AK3 show potent reverse transcriptase (RT) inhibitor activity and compounds AK4 to AK9, AK11, AK12, AK13 and AK14 show RT inhibitory activity comparable with standard rilpivirine. In docking studies, those compounds show higher G-Score which indicates higher percentage of inhibition of reverse transcriptase during in vitro screening. Insilico pharmacokinetic studies imply that synthesized derivatives have no CYP450 inhibition, no BBB penetration and good oral absorption. Virtual toxicity studies performed by using Toxtree-v 2.6.6 in various computational animal models show high LD50 values and the compounds are found to be non-carcinogenic.
