6607-92-7Relevant articles and documents
Electronic effect control of regioselectivity in the Michael-Addition inspired cascade reaction of 1,3-dimethyl-6-amino-uracil and 2-hydroxychalcones
Cui, Xin,Huang, Chao,Li, Jing-Peng,Lin, Jun-Jie,Wang, Shuang,Xia, Xian-Song
supporting information, (2022/01/15)
An unexpected Brosnted acid-catalyzed cascade reaction of 1,3-dimethyl-6-aminouracil with 2-hydroxychalcone has been developed to afford pyrido[2,3–d]pyrimidine-2,4-diones derivatives and 2,8-dioxabicyclo[3.3.1]nonane derivatives in moderate to good yield
Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors
Mellado, Marco,González, César,Mella, Jaime,Aguilar, Luis F.,Vi?a, Dolores,Uriarte, Eugenio,Cuellar, Mauricio,Matos, Maria J.
, (2021/02/12)
Monoamine oxidases (MAOs) are important targets in medicinal chemistry, as their inhibition may change the levels of different neurotransmitters in the brain, and also the production of oxidative stress species. New chemical entities able to interact selectively with one of the MAO isoforms are being extensively studied, and chalcones proved to be promising molecules. In the current work, we focused our attention on the understanding of theoretical models that may predict the MAO-B activity and selectivity of new chalcones. 3D-QSAR models, in particular CoMFA and CoMSIA, and docking simulations analysis have been carried out, and their successful implementation was corroborated by studying twenty-three synthetized chalcones (151–173) based on the generated information. All the synthetized molecules proved to inhibit MAO-B, being ten out of them MAO-B potent and selective inhibitors, with IC50 against this isoform in the nanomolar range, being (E)-3-(4-hydroxyphenyl)-1-(2,2-dimethylchroman-6-yl)prop-2-en-1-one (152) the best MAO-B inhibitor (IC50 of 170 nM). Docking simulations on both MAO-A and MAO-B binding pockets, using compound 152, were carried out. Calculated affinity energy for the MAO-A was +2.3 Kcal/mol, and for the MAO-B was ?10.3 Kcal/mol, justifying the MAO-B high selectivity of these compounds. Both theoretical and experimental structure–activity relationship studies were performed, and substitution patterns were established to increase MAO-B selectivity and inhibitory efficacy. Therefore, we proved that both 3D-QSAR models and molecular docking approaches enhance the probability of finding new potent and selective MAO-B inhibitors, avoiding time-consuming and costly synthesis and biological evaluations.
Novel isoniazid-spirooxindole derivatives: design, synthesis, biological evaluation, in silico ADMET prediction and computational studies
Bhoi, Manoj N.,Borad, Mayuri A.,Jethava, Divya J.,Pandya, Himanshu A.,Patel, Chirag N.,Patel, Hitesh D.
, (2020/07/21)
In the present scenario, the Synthesis of new and desired antimycobacterial agent has an eternal demand to resist Mycobacterium tuberculosis (MTB). The design and identification of new molecules for the treatment of tuberculosis is an important task in organic as well as medicinal chemistry research. In the present study, we have reported the combination of the desired compound using two versatile and significant moieties, isoniazid and spirooxindole derivatives. A series of novel isoniazid-spirooxindole hybrid molecules (6a-6ao) were designed, synthesized, and well-characterized by various spectroscopic methods. We have evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) strain and MDR-TB. Among them, Compound 6ab was found to be the most effective compare to other compounds. ADMET-related descriptors were to be calculated of all the compounds to predict the pharmacokinetic properties for the selection of the effective and bioavailable compounds. In addition, molecular docking and molecular dynamics studies reveal that the binding modes of all the compounds in the active site of isoniazid-resistant enoyl-ACP(COA) reductase, which helped to establish a structural basis of inhibition of Mycobacterium tuberculosis.
