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Reactions of indolo[2,3-a]furano[3,4-c]carbazole-5,7-diones with hydrazine hydrate, hydroxylamine hydrochloride, and formyl hydrazine produced the corresponding N-6-substituted indolopyrrolocarbazole glycosides with the carbohydrate residues L-arabinose, D-galactose, D-xylose, and D-ribose. The obtained compounds were studied in vitro and in vivo and showed significant antiproliferative activity against HCT-116 cells (IC50 = 10–6 – 10–7 M) and high antitumor effects on Ehrlich ascites tumor and P-388 lymphocytic leukemia models. The lifespan increase of animals in the first model ranged from 540 – 495% to 172 – 132%; in the second model, from 80 – 83% to 120 – 93%.

Twenty-four rosettes (proliferative epidermal units) in epithelial tissue are united into morphofunctional zones, where cambial cells proliferate with the formation of maternal and daughter cells and these latter ones differentiate under the influence of electrical field generated by 12 maternal cells. The number of cambial cells in morphofunctional zone of a malignant tumor is reduced at least 2-fold. Hence, the number of maternal cells is reduced to 6, which is insufficient for electric field generation and stimulation of daughter cells differentiation. The percentage of cambial cells in a benign tumor decreases 1.5 times. Daughter cells are differentiated in an electric field whose strength is below optimal, but above the threshold value at which cells do not differentiate; hence, differentiation is incomplete.

The basal layer of mouse skin epidermis consists of special structures - rosettes functionally arranged in zones including about 20 rosettes. The rosette contains a central cambial cell; after division of this cell the mother cell remains in the center of the rosette and the daughter cell migrated to the center of a free rosette. The mother and daughter cells are dipole cells (sources of electric field). If the disposition of mother cells is unidirectional and they predominate over daughter cells, the latter cells transform into other cells, i. e. are differentiated.

In recent years, considerable effort of researchers has been devoted to studying the cellular signal systems, that is, the pathways of information transfer inside the cell. A significant role in this process is played by the transport of K, Na, Ca, Mg and some other ions. In connection with this, it is interesting to study ionophores – compounds with a special molecular structure that renders them capable of carrying small ions through lipid barriers. Ionophores are stable both chemically and biologically. These compounds either contain macrocyclic structural fragments or are capable of forming such structures by means of hydrogen bonds. Macrocyclic ionophores of natural origin can be considered as prototypes of crown compounds [1]. As is known, actinomycin D forms complexes with Na analogous to those formed by crown compounds [2, 3]. The crown groups can be introduced into the structure of a DNA complexon [4], but the effect of such groups upon the antitumor activity of such complexes has not been systematically studied. It was suggested that the complexation of actinomycin D with Na is related to the properties of cyclopeptide groups of this antibiotic, which are composed predominantly of N-alkylamino acids [5, 6]. We suggested that introducing crown groups free of cationoid centers into the amide groups of actinocin amides would lead to new compounds with properties close to those of actinomycin D. In this context, we have synthesized actinocin derivatives containing benzo-15-crown-5 and benzo-18-crown-6 groups attached via amide bonds. We studied both compounds with the crown fragments introduced immediately in the amide groups of actinocin diamides [7] and those in which with the fragments were separated from the amide groups by amino acid residues (glycine, -alanine, and 6-aminocaproic acid) [8]. The compounds studied were synthesized as described previously [7, 8].