Browsing by Subject "Ligands"

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    Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Safe, Stephen
    Although endogenous ligands for the orphan nuclear receptor 4A1 (NR4A1, Nur77), NR4A2 (Nurr1), and NR4A3 (Nor-1) have not been identified, several natural products and synthetic analogs bind NR4A members. These studies are becoming increasingly important since members of the NR4A subfamily of 3 receptors are potential drug targets for treating cancer and non-cancer endpoints and particularly those conditions associated with inflammatory diseases. Ligands that bind NR4A1, NR4A2, and NR4A3 including Cytosporone B, celastrol, bis-indole derived (CDIM) compounds, tryptophan/indolic, metabolites, prostaglandins, resveratrol, piperlongumine, fatty acids, flavonoids, alkaloids, peptides, and drug families including statins and antimalarial drugs. The structural diversity of NR4A ligands and their overlapping and unique effects on NR4A1, NR4A2, and NR4A3 suggest that NR4A ligands are selective NR4A modulators (SNR4AMs) that exhibit tissue-, structure-, and response-specific activities. The SNR4AM activities of NR4A ligands are exemplified among the Cytosporone B analogs where n-pentyl-2-[3,5-dihydroxy-2-(nonanoyl)]phenyl acetate (PDNPA) binds NR4A1, NR4A2 and NR4A3 but activates only NR4A1 and exhibits significant functional differences with other Cytosporone B analogs. The number of potential clinical applications of agents targeting NR4A is increasing and this should spur future development of SNR4AMs as therapeutics that act through NR4A1, NR4A2 and NR4A3.
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    Synthesis and Photophysical Properties of Cyclometallated Pt(II) 1,2-Benzenedithiolate Complexes and Heterometallic Derivatives Obtained from the Addition of [Au(PCy3)]+ Units
    (American Chemical Society, 2012-04-13) Juliá Hernández, Fabio; Jones, Peter G.; González Herrero, Pablo; Química Inorgánica
    The cyclometalated compounds [Pt(C^N)(HC^N)Cl] [HC^N = 2-phenylpyridine (Hppy; 1a), 1-(4-tert-butylphenyl)isoquinoline (Htbpiq; 1b)] react with 1,2-benzenedithiol, t-BuOK, and Bu4NCl in a 1:1:2:1 molar ratio in CH2Cl2/MeOH to give the complexes Bu4N[Pt(C^N)(bdt)] [bdt = 1,2-benzenedithiolate; C^N = ppy (Bu4N2a), tbpiq (Bu4N2b)]. In the absence of Bu4NCl, the same reactions afford solutions of K2a and K2b, which react with [AuCl(PCy3)] to give the neutral heterometallic derivatives [Pt(C^N)(bdt){Au(PCy3)}] [C^N = ppy (3a), tbpiq (3b)]. The cationic derivatives [Pt(C^N)(bdt){Au(PCy3)}2]ClO4 [C^N = ppy (4a), tbpiq (4b)] are obtained by reacting 3a and 3b with acetone solutions of [Au(OClO3)(PCy3)]. The crystal structures of 3b and 4b reveal the formation of short Pt···Au metallophilic contacts in the range 2.929–3.149 Å. Complexes 3b, 4a, and 4b undergo dynamic processes in solution that involve the migration of the [Au(PCy3)]+ units between the S atoms of the dithiolate. Complexes Bu4N2a and 2b display a moderately solvatochromic band in their electronic absorption spectra that can be ascribed to a transition of mixed ML′CT/LL′CT character (M= metal; L = bdt; L′ = C^N; CT = charge transfer), while their emissions are assignable to transitions of the same orbital parentage but from triplet excited states. The successive addition of [Au(PCy3)]+ units to the anions 2a and 2b results in an increase in the absorption and emission energies attributable to lower highest occupied molecular orbital energies. Additionally, the characteristics of the absorption and emission spectra of the heterometallic derivatives indicate a gradual loss of LL′CT character in the involved electronic transitions, with a concomitant increase of the L′C and ML′CT contributions.