- Synthesis, biological evaluation and molecular modeling studies of psammaplin A and its analogs as potent histone deacetylases inhibitors and cytotoxic agents
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In this study, a concise synthetic method of psammaplin A was achieved from 3-bromo-4-hydroxybenzaldahyde and hydantoin through a four-step synthesis via Knoevenagel condensation, hydrolysis, oximation and amidation in 37% overall yield. A collection of novel psammaplin A analogs focused on the variations of substituents at the benzene ring and modifications at the oxime moiety were synthesized. Among all the synthesized compounds, 5d and 5e showed better HDAC inhibition than psammaplin A and comparable cytotoxicity against four cancer cell lines (PC-3, MCF-7, A549 and HL-60). Molecular docking and dynamics simulation revealed that (i) hydrogen atom of the oxime group interacts with Asp99 of HDAC1 through a water bridged hydrogen bond and (ii) a hydroxyl group is optimal attached on the para-position of benzene, interacting with Glu203 at the entrance to the active site tunnel.
- Wen, Jiachen,Bao, Yu,Niu, Qun,Liu, Jiang,Yang, Jinyu,Wang, Wanqiao,Jiang, Tao,Fan, Yinbo,Li, Kun,Wang, Jian,Zhao, Linxiang,Liu, Dan
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supporting information
p. 4372 - 4376
(2016/08/18)
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- SUBSTITUTED BETA-PHENYL-ALPHA-HYDROXY PROPANOIC ACID, SYNTHESIS METHOD AND USE THEREOF
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The present invention relates to a compound of the formula (I), wherein R1, R2 and R3 are each independently selected from H, OH, F, Cl, Br, methoxy and ethoxy; or alternatively, R1 and R2 together form -OCH2O-, R3 is selected from H, OH, methoxy, ethoxy and halogens; R4 is OH or acyloxy; R5 is cycloalkoxyl, amino and substituted amino, and when R5 is selected from amino, at least one of R1, R2 and R3 is not H. The present invention further relates to a process for synthesizing a compound of the formula (I), and use of the compound of the formula (I) in the manufacture of a medicament for the prevention or treatment of cardiovascular or cerebrovascular diseases.
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Page/Page column 9
(2009/02/10)
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- Studies on arylmethyltriazinone derivatives-Part II. Synthesis and antifungal properties of 2-aminomethyl-4-(arylidene)amino-6-arylmethyl-3-mercapto-1, 2,4-triazin-5(4H)-ones
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The preparation of twenty new 2-aminomethyl-4-(arylidene)amino-6-arylmethyl-3-mercapto-1,2,4-triazin-5(4H)- ones(4) is described. The structural elucidation of all the compounds is carried out on the basis of analytical and spectral data. The newly synthesized compounds are evaluated for their antifungal activity against Candida albicans and Paecileomyces variotti.
- Holla,Gonsalves,Shivananda
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- Potent, selective tetrahydro-β-carboline antagonists of the serotonin 2B (5HT(2B)) contractile receptor in the rat stomach fundus
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A series of potent, selective 5HT(2B) receptor antagonists has been identified based upon yohimbine, with SAR studies resulting in a 1000-fold increase in 5HT(2B) receptor affinity relative to the starting structure (- log K(B)s > 10.0 have been obtained). These high-affinity tetrahydro-β- carboline antagonists are able to discriminate among the 5HT2 family of serotonin receptors, with members of the series showing selectivities of more than 100-fold versus both the 5HT(2A) and 5HT(2C) receptors based upon radioligand binding and functional assays. As the first compounds reported with such selectivity and enhanced receptor affinity, these tetrahydro-β- carboline antagonists are useful tools for elucidating the role of serotonin acting at the 5HT(2B) receptor in normal and disease physiology.
- Audia, James E.,Evrard, Deborah A.,Murdoch, Gwyn R.,Droste, James J.,Nissen, Jeffrey S.,Schenck, Kathy W.,Fludzinski, Pawel,Lucaites, Virginia L.,Nelson, David L.,Cohen, Marlene L.
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p. 2773 - 2780
(2007/10/03)
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