Asymmetric Phenyl Substitution: An Effective Strategy to Enhance the Photosensitizing Potential of Curcuminoids

Abstract

Curcumin has been demonstrated to exhibit photosensitized bactericidal activity. However, the full exploitation of curcumin as a photo-pharmaceutical active principle is hindered by fast deactivation of the excited state through the transfer of the enol proton to the keto oxygen. Introducing an asymmetry in the molecular structure through acting on the phenyl substituents is expected to be a valuable strategy to impair this undesired de-excitation mechanism competing with the therapeutically relevant ones. In this study, two asymmetric curcumin analogs were synthesized and characterized as to their electronic-state transition spectroscopic properties. Fluorescence decay distributions were also reconstructed. Their analysis confirmed the substantial stabilization of the fluorescent state with respect to the parent compound. Nuclear magnetic resonance experiments were performed with the aim of determining the structural features of the keto–enol ring and the strength of the keto-enol hydrogen bond. Electronic structure calculations were also undertaken to elucidate the effects of substitution on the features of the keto–enol semi-aromatic system and the proneness to proton transfer. Finally, their singlet oxygen-generation efficiency was compared to that of curcumin through the 9,10-dimethylanthracene fluorescent assay.

Synthesis, Characterization, Fluorescence Properties, and DFT Modeling of Difluoroboron Biindolediketonates

“…Solvent Like other enolized β-diketones [19][20][21][22][23][24][25][26], the BF 2 bdk compounds show, in all the solvents, a main absorption band peak in the blue portion of the visible spectrum, between 428 nm (4b in toluene) and 452 nm (4c in dimethyl sulfoxide), and a much fainter absorption in the UVB (around 280 nm). The spectral line shape of the main peak exhibits a substructure, with a shoulder around 400 nm.…”

“…The improved efficiency in photosensitizing singlet oxygen ( 1 O 2 ) generation of the BF 2 bdk with respect to the corresponding bdk compounds was assessed in ethanol (the most biocompatible solvent in our panel) by exploiting the DMA fluorescence assay [ 29 ]. Due to the marked tendency of this sensor to oxidate, a fresh 1 mM concentrated stock of DMA in ethanol was prepared from the powdered compound immediately before each singlet oxygen generation measurement according to the procedure detailed elsewhere [ 25 ]. Solutions of the BF 2 bdk at approximate concentration of 1 µM were prepared and their exact concentration determined spectrophotometrically using the molar extinction coefficients reported in Table 2 .…”

1,3-diketone analogs as selective lysyl hydroxylase 2 (LH2) antagonists

“…Its intrinsic ability to participate in metal chelation and hydrogen bonding owing to tautomerism makes the 1,3-diketone a promising scaffold for intermediates in various organic reactions, metal-organic hybrid materials, and novel drug development. [42][43][44][45][46][47] Here we report the development of a series of antagonists (compounds 1-18 in Figure 2) based on 1,3-diketone analogs against LH2. Compound 13 was considered in detail and was shown to inhibit the enzymatic activity of LH2 in vitro with some selectivity over other isoforms (LH1 and LH3) and hinder the migration of 344SQ lung adenocarcinoma cells (LH2b highly expressed) in a dose-dependent manner.…”