Membrane perturbations induced by new analogs of neocryptolepine.

Indoloquinoline alkaloids represent an important class of antimalarial, antibacterial and antiviral compounds. Indolo[2,3-b]quinolines are a family of DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of neocryptolepine, an alkaloid traditionally used in African folk medicine. These cytotoxic substances are promising anticancer agents. Active representatives of indolo[2,3-b]quinolines affect model and natural membranes. The distinct structure and hydrophobicity of the compounds leads to marked differences in the disturbing effects on membrane organization and function. Our results also indicated a strong relationship between the presence of the chain and the Poct of the molecule as well as the capacity for incorporation into carboxyfluorescein-trapped liposomes in the 0.02-0.06 mM range. Moreover, a correlation between binding to neutral dimyristoylphosphatidylcholine (DMPC) or negative charged dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DMPC:DMPG, 9:1 w/w) liposomes, as well as to erythrocyte ghosts and pKa, was also found. All the compounds cause hemolysis in isotonic conditions with concentration causing 50% hemolysis (HC50) in the 0.12-0.88 mM range. The concentration-dependent inhibitory effect of the tested agents on erythrocyte ghosts' acetylcholinesterase activity was also studied.

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.

A description of Macrobiotus horningi sp. nov. and redescriptions of M. maculatus comb. nov. Iharos, 1973 and M. rawsoni Horning et al., 1978 (Tardigrada: Eutardigrada: Macrobiotidae: hufelandi group).

We examined microscope slides from Horning and Iharos tardigrade collections from Museum of New Zealand Te Papa Tongarewa in Wellington and Hungarian Natural History Museum in Budapest with species of the Macrobiotus hufelandi group. Based on this material we describe one new species, Macrobiotus horningi sp. nov., and re-describe two others, M. maculatus comb. nov. Iharos, 1973 and M. rawsoni Horning et al., 1978. With the oral cavity armature of the patagonicus type and chorion of the hufelandi type, Macrobiotus horningi sp. nov. is most similar to: M. personatus Biserov, 1990, M. sandrae Bertolani & Rebecchi, 1993, M. serratus Bertolani et al., 1996, M. sottilei Pilato et al., 2012, M. terminalis Bertolani & Rebecchi, 1993 and M. vladimiri Bertolani et al., 2011, but it differs from them in morphological and morphometric traits. With eggs of the maculatus type, M. maculatus comb. nov. is most similar to: M. biserovi Bertolani et al., 1996, M. denticulatus Dastych, 2002, M. macrocalix Bertolani & Rebecchi, 1993 and M. ramoli Dastych, 2005, but differs from them in morphological and morphometric characters.