59923-03-4Relevant articles and documents
Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as SmHDAC8 Inhibitors for the Treatment of Schistosomiasis
Bayer, Theresa,Chakrabarti, Alokta,Lancelot, Julien,Shaik, Tajith B.,Hausmann, Kristin,Melesina, Jelena,Schmidtkunz, Karin,Marek, Martin,Erdmann, Frank,Schmidt, Matthias,Robaa, Dina,Romier, Christophe,Pierce, Raymond J.,Jung, Manfred,Sippl, Wolfgang
, p. 1517 - 1529 (2018/08/01)
Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prepared as potential inhibitors of Schistosoma mansoni histone deacetylase 8 (SmHDAC8). The crystal structures of SmHDAC8 with four inhibitors provided insight into the binding mode and orientation of molecules in the binding pocket as well as the orientation of its flexible amino acid residues. The compounds were evaluated in screens for inhibitory activity against schistosome and human HDACs. The most promising compounds were further investigated for their activity toward the major human HDAC isotypes. The most potent inhibitors were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Two of the compounds showed significant, dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
Probable Absence of Lattice Control of cis-trans-Isomerization in 2-Ethoxy-cis-cinnamic Acid
Bryan, Robert F.,Hartley, Paul
, p. 191 - 194 (2007/10/02)
The crystal structure of the title compound has been determined from 1380 reflections measured by diffractometer.Crystals are orthorhombic, space group Pbca, with a=10.811(3), b=12.137(3), c=15.233(4) Angstroem, Z=8.The structure was solved by direct methods and refined by least-squares to give R 0.041.The acid is present in the crystal in a non-planar conformation and forms centrosymmetric hydrogen-bonded dimers (O-H...O, 2.651 Angstroem).The plane of the double bound, C(1)-C(β)-C(α)-C(7), is inclined to the plane of the phenyl ring at 59.4 deg, and to that of the carboxy-group at 12.3 deg.There is a limiting intramolecular contact between the carbonyl oxygen O(1) and C(6) of the phenyl ring.It has been postulated that the solid-state cis-trans isomerization of such cinnamic acids is lattice controlled, through interactions between >C=C bonds in neighbouring molecules in close contact (4.0-4.4 Angstroem).It is shown that this crystal, where isomerization is known to occur, contains no such suitable contacts.
