Investigation of NPB Analogs That Target Phosphorylation of BAD-Ser99 in Human Mammary Carcinoma Cells.

The design and development of a small molecule named NPB [3-{(4(2,3-dichlorophenyl)piperazin-1-yl}{2-hydroxyphenyl)methyl}-N-cyclopentylbenzamide], which specifically inhibited the phosphorylation of BAD at Ser99 in human carcinoma cells has been previously reported. Herein, the synthesis, characterization, and effect on cancer cell viability of NPB analogs, and the single-crystal X-ray crystallographic studies of an example compound (4r), which was grown via slow-solvent evaporation technique is reported. Screening for loss of viability in mammary carcinoma cells revealed that compounds such as 2[(4(2,3-dichlorophenyl)piperazin-1-yl][naphthalen-1-yl]methyl)phenol (4e), 5[(4(2,3-dichlorophenyl)piperazin-1-yl][2-hydroxyphenyl)methyl)uran-2-carbaldehyde (4f), 3[(2-hydroxyphenyl][4(p-tolyl)piperazin-1-yl)methyl)benzaldehyde (4i), and NPB inhibited the viability of MCF-7 cells with IC50 values of 5.90, 3.11, 7.68, and 6.5 µM, respectively. The loss of cell viability was enhanced by the NPB analogs synthesized by adding newer rings such as naphthalene and furan-2-carbaldehyde in place of N-cyclopentyl-benzamide of NPB. Furthermore, these compounds decreased Ser99 phosphorylation of hBAD. Additional in silico density functional theory calculations suggested possibilities for other analogs of NPB that may be more suitable for further development.

Influence of interface structure in redox and optical properties of thio and seleno-Ureidopeptide functionalized bimetallic gold nanocluster: DFT study.

A simple cluster-ligand interaction model is introduced to describe the surface passivation of bimetallic gold clusters by SUP (Thioureidopeptide) and SeUP (Selenoureidopeptide) ligands. The conformational search based on neutral peptide binding modes and their computed interaction energies show the existence of various structural isomers within 10 kcal mol-1. Further, the negatively charged deprotonated peptide was found to strongly interact with metal cluster through the carboxylate unit. Irrespective of the mode of binding and configuration the metal cluster found to exist in parent geometry in all three charge states. The calculated HOMO-LUMO gap of ligated clusters predicts an increase in chemical stability after the ligation. Moreover, the ligation was found to decrease the energy required for oxidation and reduction. The excited-state calculations indicate absorption maxima at 200-400 nm corresponds to the LMCT transition. In all the hybrid cluster models the donor and acceptor end of the peptide were found to remain intact. However, the charge migration dynamics observed only in the homo-metallic gold-ligand hybrids, owing to the larger charge separation.

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach.

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.