Lukasz Kaczmarek

Selective Reduction of the N-O Bond in Heteroaromatic N-Oxides by TiCl4/SnCl2

Abstract Heteroaromatic N-oxides bearing various functionalities are readily and selectively converted under mild conditions into the corresponding bases using TiCl4/SnCl2.

New derivatives of 11-methyl-6-[2-(dimethylamino)ethyl]-6H-indolo[2,3-b]quinoline as cytotoxic DNA topoisomerase II inhibitors.

Novel indolo[2,3-b]quinoline derivatives substituted at N-6 and C-2 or C-9 positions with (dimethylamino)ethyl chains linked to heteroaromatic core by ether, amide or amine bonds, were manufactured and evaluated in vitro for their cytotoxic activity against several cell lines of different origin including multidrug resistant sublines and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. It was found, that all compounds show cytotoxic activity against cell lines tested, including multidrug resistant LoVo/DX, MES-SA/DX5 and HL-60 sublines. The tested compounds induce the G(2)M phase cell cycle arrest in Jurkat cells, and inhibit topoisomerase II activity.

Proton transfer along the internal hydrogen bonds in excited Schiff bases. Photochromism in symmetric systems with two equivalent reaction sites

Abstract Photophysics (phototautomeric fluorescence, transient absorption) and quantum-chemical study (Molecular Mechanics, INDO/S) of the photochromic Schiff bases - derivatives of salicylideneaniline - were reported. It was shown that in molecules with two equivalent internal H-bonds only one proton is translocated to create the monoketo-tautomer with a zwitterionic character. In contrast, the same molecule in the ground state has a strong tendency to remain symmetric.

A carboline derivative as a novel mammalian DNA topoisomerase II targeting agent

The DNA intercalating, ellipticine analog drug, 5,11-dimethyl-5H-indol[2,3-b]quinoline, is able to stabilize in vitro the topoisomerase II-DNA cleavable complex and to induce DNA breaks in BPV I episome in rat fibroblasts. Cytotoxicity studies with DC3F cells resistant to ellipticine strongly suggest that topoisomerase II is a cellular target involved in the mechanism of cytotoxic action of this carboline derivative.

Liposomal Formulation of DIMIQ, Potential Antitumor Indolo(2,3-b)Quinoline Agent and Its Cytotoxicity on Hepatoma Morris 5123 Cells

The cytotoxic and antitumor activity of DIMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline), synthetic analog of neocryptolepine, makes this compound a potential antitumor agent. An attempt to obtain liposomal form of DIMIQ·HCl was undertaken in the present study. Standard experimental conditions were chosen and information on the physicochemical parameters of the liposome dispersion containing studied indoloquinoline agent was collected. The effective and efficient encapsulation of DIMIQ·HCl (66.6%) in conventional liposomes (FAT-MLV, DMPC:DMPG 7:3 w/w at pH 7.0), uniformity of the size of liposomal vesicles, and high stability at pH 6.5 were demonstrated. Hemolysis of sheep erythrocytes induced by free form of DIMIQ·HCl was dramatically decreased after addition of liposome-entrapped DIMIQ·HCl. Treatment of hepatoma Morris 5123 cells for 24 hr with different concentrations of both free and its liposomal formulation of DIMIQ·HCl resulted in significant changes in cell morphology accompanied by reduction of cell viability.

Mild Reductive Deoximation with TiCl4/NaI Reagent System

Abstract The application of the TiCl4/NaI reagent system in the reductive cleavage of oximes under mild conditions is reported.