Photophysical and Redox Properties of a Series of Phthalocyanines: Relation with Their Photodynamic Activities on TF-1 and Daudi Leukemic Cells

Abstract— The photodynamic therapy (PDT) efficiency of five phthalocyanines, chloroaluminum phthalocyanine (AlPc), dichlorosilicon phthalocyanine (SiPc), bis (tri- n -hexylsi-loxy)silicon phthalocyanine (PcHEX), bis (triphenyl-siloxy)silicon phthalocyanine (PcPHE) and nickel phthalocyanine (NiPc), was assessed on two leukemic cell lines TF-1 and erythroieukemic and B lymphoblastic cell lines, Daudi, respectively. AlPc showed the best photocytotox-icity leading to 0.008 surviving fraction at 2 × 10⁻⁹ M for TF-1 and 4 × 10⁻⁹ M for Daudi. At 5 × 10⁻⁷ M , SiPc and PcHEX induced a significant photokilling, whereas NiPc and PcPHE were inactive. Laser flash photolysis and photoredox properties of the phthalocyanines were investigated to try to relate these parameters with the biological effects. AlPc showed the longest triplet lifetime: 484 fis in dimethyl sulfoxide/H₂O. This value was increased up to 820 u.s when AlPc was complexed with human serum albumin used as a membrane model. Such an enhancement was not observed with the silicon phthalocyanines. Upon irradiation, all the phthalocyanines generated singlet oxygen with 0.29–0.37 quantum yield values. The reduction potentials of the excited states obtained from measurement in the ground state and energy of the excited triplets show that AlPc is the best electron acceptor. The in vitro photocytotoxicity observed and the measured parameters are in agreement with a key role of electron transfer in PDT assays involving these phthalocyanines.     

Gear effect—10 : Conformational aspects of the positive or negative buttressing effects of methyl groups: polymethylpyridines

The effect of the shape of a methyl group on reactivity, which cannot be accounted for by considering a methyl group as a spherical substituent with the appropriate van der Waals radius, was considered in kinetics of alkylalion of substituted pyridines and barriers to rotation and ground state conformations of an isopropyl group attached to a planar framework. The perturbation of a methyl group by an o-methyl group is accounted for by a unique conformational explanation which involves the polyhedral shape of the methyl group.     

Crystal structure of a new precursor of radical-clock based on the norbornenyl framework

The crystal of 5-phenyl-2-endo-(propane-2-sulfonyl)-bicyclo[2-2-1]hept-5-ene-2-carbonitrile1, a new radical-clock is described. The structure has confirmed the configuration for the positions of the phenyl and sulfonyl groups. In the crystal, the radical precursor carbon atom of the propane group is not neighbouring with the double bond of the norbornene. Nevertheless, in solution, it may be expected an ideal conformation with a short intergroup distance leading to a cyclization process. Crystal data: C₁₇H₁₉NO₂S, triclinic, space group P−1,a=6.567 (3),b=10.407(5),c=12.610(6), α=110.48(2), β=95.88(2), λ=102.67(3).     

Silk Fibroin-Coated Liposomes as Biomimetic Nanocarrier for Long-Term Release Delivery System in Cancer Therapy

Despite much progress in cancer therapy, conventional chemotherapy can cause poor biodistribution and adverse side-effects on healthy cells. Currently, various strategies are being developed for an effective chemotherapy delivery system. Silk fibroin (SF) is a natural protein used in a wide range of biomedical applications including cancer therapy due to its biocompatibility, biodegradability, and unique mechanical properties. In this study, SF-coated liposomes (SF-LPs) were prepared as a biomimetic drug carrier. Physicochemical properties of SF-LPs were characterized by Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering, zeta potential measurement, and transmission electron microscopy (TEM). In vitro release of SF-LPs loaded with doxorubicin (DOX-SF-LPs) was evaluated over 21 days. Anticancer activity of DOX-SF-LPs was determined against MCF-7 and MDA-MB231 cells using the MTT assay. SF-LPs containing 1% SF exhibited favorable characteristics as a drug carrier. SF coating modified the kinetics of drug release and reduced the cytotoxic effect against L929 fibroblasts as compared to the uncoated liposomes containing cationic lipid. DOX-SF-LPs showed anticancer activity against breast cancer cells after 48 h or 72 h at 20 μM of DOX. This approach provides a potential platform of long-term release that combines biocompatible SF and phospholipids for cancer therapy, achieving efficient drug delivery and reducing side-effects.     

EFFICIENT PHOTODYNAMIC ACTION OF VICTORIA BLUE BO AGAINST THE HUMAN LEUKEMIC CELL LINES K-562 AND TF-1

Abstract— Photodynamic induced cytotoxicity by Victoria blue BO (VB-BO), merocyanine 540 (MC540), Nile blue A (NB) and 4-tetrasulfonatophenyl-porphyrin (4-TSPP) has been studied on two human leukemic cell lines: K-562 and TF-1. Cells were incubated with dyes and irradiated with different doses of white light. Cell survival was assessed by propidium iodide (PI) staining using flow cytometry analysis. Concentrations of 5 x 10 ⁸ M VB-BO were found to kill 75% of cells, and a concentration of 1 × 10⁻⁷ M induced more than 99% of cell killing. To obtain the same cytotoxic level, the presence of 2.6 × 10⁻⁵ M of MCS40 during irradiation was needed. Under the conditions used, NB was ineflective as a photosensitizer, although uptake studies showed that this dye was taken by the cells in much greater amounts than any other studied dye. Cell cycle distribution of TF-1 cells, surviving MC540 or VB-BO photoscnsitization has bccn studied by flow cytometry analysis after staining with Hoechst 33342 and PI. It was found that cells in G₁ phase were slightly more resistant toward MCS40– and VB-BO-mediated photosensitization than cells in other phascs of the ccll cycle     

Search for strategies by computer: the CONAN approach. Application to steroid and taxane frameworks

We describe the CONAN (CONnectivity ANalysis) program the aim of which is to search for strategies by simplification of the target skeleton by different types of disconnection. The options available for the disconnections of the target are: add one bond, delete one or two bonds, search for linear precursors, for convergent strategies, for precursors containing a given number of rings and linear chains, and then disconnection of rings by formal [x+y] reaction types like [2+2], [4+2], etc. Taxane and steroid skeletons have been studied. CONAN runs on PC's microcomputers.     

Etude du mécanisme de la réaction de hantzsch des thiazoles. II. premiére étape: Action des cétones-α halogénées sur les thioamides

The mechanism of the Hantzsch heterocyclization reaction is studied. The α-haloketones behavior is an example of ambident reactivity. We show, by kinetic determinations and from literature data, that the interaction of α-haloketones with thioamides begins by a direct substitution of the halogen atom by the sulfur atom.