Identification of Adenosine Deaminase Inhibitors by Metal-binding Pharmacophore Screening
Adenosine deaminase (ADA) is a human mononuclear Zn2+ metalloenzyme that converts adenosine to inosine. ADA is a validated drug target for cancer, but there has been little recent work on the development of new therapeutics against this enzyme. The lack of new advancements can be partially attributed to an absence of suitable assays for high-throughput screening (HTS) against ADA. To facilitate more rapid drug discovery efforts for this target, an in vitro assay was developed that utilizes the enzymatic conversion of a visibly emitting adenosine analogue to the corresponding fluorescent inosine analogue by ADA, which can be monitored via fluorescence intensity changes. Utilizing this assay, a library of ~350 small molecules containing metal-binding pharmacophores (MBPs) was screened in an HTS format to identify new inhibitor scaffolds against ADA. This approach yielded a new metal-binding scaffold with a Ki value of 26±1 μM.
Adamek, Rebecca N.,Ludford, Paul,Duggan, Stephanie M.,Tor, Yitzhak,Cohen, Seth M.
supporting information
p. 2151 - 2156
(2020/10/19)
Oxorhenium(V) complexes with naphtholate-oxazoline ligands in the catalytic epoxidation of olefins
Four oxorhenium(V) complexes 3a-d equipped with naphtholate-oxazoline based ligands 2a-d have been prepared and characterized by NMR, IR and mass spectroscopy as well as elemental analysis. Ligands 2a-d were prepared in a two-step procedure from commercially available starting materials. Ligands 2a-b and 2c-d are regioisomers to each other regarding the position of the -OH group and oxazoline moiety on the naphthol ring. Reaction of 2a-d with (NBu 4)[ReOCl4] in methanol under reflux gave oxorhenium(V) complexes 3a-d of the type [ReOCl(L)2] as green solids in acceptable to good yields. The molecular structures of complexes 3b and 3d have been determined via single crystal X-ray diffraction analysis and both display a distorted octahedral geometry. Complexes 3a-d are active catalysts for the epoxidation of cyclooctene with tert-butylhydroperoxide (TBHP) showing moderate conversions between 41% and 65%.
Terfassa, Belina,Schachner, J?rg A.,Traar, Pedro,Belaj, Ferdinand,M?sch Zanetti, Nadia C.
p. 141 - 145
(2014/05/06)
The influence of intramolecular hydrogen bonding on the order parameter and photostability properties of dichroic azo dyes in a nematic liquid crystal host
It has been demonstrated that intramolecular hydrogen bonding in two classes of dichroic azo dyes has a generally detrimental effect on order parameter in a nematic liquid crystal host. Derivatives of 4-(N,N- diethylamino)-4'-nitroazobenzene with hydroxy groups intramolecularly hydrogen bonded to the azo group show lower order parameters in E7 nematic liquid crystal than the parent dye, but higher order parameters than corresponding methoxy dyes. 1-Arylazo-2-naphthols with a hydrogen bonding carboxamide group in position 3 exist exclusively in the hydrazone form and show even lower order parameters. Intramolecular hydrogen bonding also has a deleterious effect on photochemical stability.