The synthesis of indolo[2,3-b]quinoline derivatives with a guanidine group: highly selective cytotoxic agents.

The synthesis of indolo[2,3-b]quinoline derivatives containing guanidine, amino acid or guanylamino acid substituents as well as their in vitro evaluation for the cytotoxic and antifungal activity are reported. The influence of the guanidine group on the selective cytotoxic and hemolytic properties of indolo[2,3-b]quinoline was investigated. Most of the compounds displayed a high cytotoxic activity in vitro and two of the most promising compounds (3 and 12) exhibited a high selectivity between normal and cancer cell-lines. The cytotoxic activity of compound 3 was about 600-fold lower against normal fibroblasts than against A549 and MCF-7 cancer cell lines. Novel entities acted as the DNA-intercalators when tested using a DNA-methyl green assay but demonstrated zero or low hemolytic activity in comparison to their unsubstituted analogs. The mechanism of action was studied for guanidine derivatives 3 and 12 and both compounds were found to be very effective inducers of apoptosis.

Identification and physicochemical characteristics of temozolomide process-related impurities.

In this article the crystal structures of the starting material TZ-5 and the key intermediate TZ-6 of temozolomide (TZ-7), an anticancer therapeutic agent, are presented, together with their spectroscopic and thermal characteristics. Both compounds crystallize in the triclinic P-1 space group. X-ray crystallography studies proved that the compound TZ-6 exists as a monohydrate. A complete structural assignment was obtained for the signals in the 1H-, 13C- and 15N-nuclear magnetic resonance spectra and the structures were confirmed by Fourier-Transform infrared and Raman spectroscopy. The article describes the importance of the high purity of TZ-6 during the small-scale plant production of TZ-7 in a desired polymorphic form III with the purity higher than 99.50%, according to an HPLC method.