Novel "Oxicobalamin+Ascorbic acid," "Teraphthal+Ascorbic acid," and "Efiter+Ascorbic acid" binary catalytic systems (BCS) have been studied in the pre-clinical experiments and clinical trials. It was shown in experiments that Oxycobalamin, Teraphthal, and Efiter-based BCS demonstrated moderate antitumor efficiency against murine and rat transplanted tumors of various histogenesis, as well as high modifying activity for different official antistatic agents, radiotherapy, chemo-radiotherapy, and local laser-induced hyperthermia. The studied BCS had no pronounced toxicity in mice, rats, or dogs, so they were considered to be moderately hazardous pharmacologic agents. Revealed toxic and side effects of BCS were dose-dependent and totally reversible. Clinical trials of the BCS demonstrated good tolerability in cancer patients with exhausted possibilities of antitumor treatment and moderate antitumor efficacy. Partial regress and stabilization of the malignant processes were observed with various routes of catalysts administration.

The experience of the joint research by the Department of Chemistry, Lomonosov Moscow State University, and the Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center" (FSBSI "N.N. Blokhin RCRC"), on the application of medium-intensity ultrasound in combination with chemotherapy and sonosensitizers in the treatment of cancer diseases was summarized. A cycle of preclinical trials showed that the method allows enhancing the damaging effect of ultrasound on the tumor, while no metastasis-promoting and toxic effects are exerted. The combined method is being currently tested in clinical trials.

The efficacy of a novel anti-tumor agent binaric catalitic system “teraphtal + ascorbic acid” [BCS (T+A)], generating reactive oxygen species, may depend on the activity of enzymes of the cellular antioxidant defense system including catalase (CAT). To evaluate the role of CAT in cancer cell defense from oxidative stress induced by BCS (T+A), we studied the following biomarkers: the expression level and basal activity of CAT in cells, and its sensitivity to specific inhibitor, aminotriazole (3-AT). We found that functionally active CAT was expressed constitutively in cultures of human tumor cells of different hystogenesis grown in vitro; at that the basal levels of CAT-protein expression and CAT-enzyme activity depend on cell types. The efficacy of CAT inhibiting by 3-AT (the parameter IC50 3-АТ) is the same for cells of all tested cultures, it ranges from 20 to 25 mM and does not depend on the level of CAT protein expression in cells. No direct correlation was found between the biological CAT characteristics and their sensitivity to BCS (T+A) for cells of different hystogenesis. In case of pharmacological CAT inhibition, the cytotoxic activity of BCS (T+A) is doubled, whereas the human tumor cell sensitization degree (increased sensitivity) to BCS (T+A) depends on their type.

Antineoplastic activity of Stellanin ® as drug “drops for per os intake”, its active substance 1,3-diethylbenzimidazolium triiodide and its methabolite 1,3-diethylbenzimidazolium monoiodide was studied on mouse transplantable tumors: lymphocytic leukemia P388, melanoma B16 and colon cancer AKATOL. Substances 1,3-diethylbenzimidazolium triiodide and its methabolite 1,3-diethylbenzimidazolium monoiodide didn’t reveal antineoplastic effect on mouse leukemia P388. Stellanin ® both as drug and as substance administered per os to mice with melanoma B16 and colon cancer AKATOL showed dose-dependent stable antitumor effect (70-50% tumor growth inhibition) during 2 weeks after treatment completion. The optimal schedules of Stellanin ® treatment were determined: single dose of 15-30 mg/kg 2-3 times a day during 10 days or dose of 10 mg/kg one time a day during 20 days. 1,3-diethylbenzimidazolium monoiodide with explored dose range didn’t show any antineoplastic activity.

The efficacy of a novel anti-tumor agent binaric catalitic system “teraphtal + ascorbic acid” [BCS (T+A)], generating reactive oxygen species, may depend on the activity of enzymes of the cellular antioxidant defense system including catalase (CAT). To evaluate the role of CAT in cancer cell defense from oxidative stress induced by BCS (T+A), we studied the following biomarkers: the expression level and basal activity of CAT in cells, and its sensitivity to specific inhibitor, aminotriazole (3-AT). We found that functionally active CAT was expressed constitutively in cultures of human tumor cells of different hystogenesis grown in vitro; at that the basal levels of CAT-protein expression and CAT-enzyme activity depend on cell types. The efficacy of CAT inhibiting by 3-AT (the parameter IC 50 3-АТ) is the same for cells of all tested cultures, it ranges from 20 to 25 mM and does not depend on the level of CAT protein expression in cells. No direct correlation was found between the biological CAT characteristics and their sensitivity to BCS (T+A) for cells of different hystogenesis. In case of pharmacological CAT inhibition, the cytotoxic activity of BCS (T+A) is doubled, whereas the human tumor cell sensitization degree (increased sensitivity) to BCS (T+A) depends on their type.

The drug Stellanin ® (ST) is original substance designed by “Pharmpreparat” company. ST has local and system wide spectrum antibacterial activity, anti-inflammation and regenerating properties. Active component of ST is iodine-containing heterocyclic compound 1,3-diethylbenzimidazolium triiodide. In water solutions ST slowly releases active molecular of iodine with production of 1,3-diethylbenzimidazolium monoiodide (DEBI-M). It is known that some of antiinflammation drugs have anticancer effect. The purpose of this article is to estimate direct cytotoxic activity of ST and its metabolite DEBI-M on human tumor cells in vitro. MTT-test was used to estimate cytotoxic activity. It was shown that ST demonstrated cytotoxic activity on colon carcinoma LS174T cell line (IC50=10 mkM, 2,5 h of incubation) in dose-dependent manner. Cells LS174T demonstrated moderate sensitivity to DEBI-M (IC50=330 mkM). In accordance of the results of the present studying ST is recommended for the investigation of antitumor activity in vivo.

In work the efficacy and tolerance of the binary catalytic systems with teraftal, oxycobalamin or ephyther as the catalyzators with ascorbic acid as the reducer by the intrapleural administration to mice with i.p. transplanted tumors is described. It was shown through efficacy of malignant pleurisy treatment, pleurodesis inducing and «acute» toxicity that the most perspective for clinical investigation are Oc+AA and Tph+AA. Tph+AA with molar parity of components as 1:100 demonstrates the best therapeutically data with high pleu-rodesis inducing, terapeutical index TI>1,5. Eph+AA with the used dosage do not demonstrate enough efficacy.

Новые 2,3-секо-тритерпеновые амиды получены взаимодействием хлорангидрида 2,3-секо-1-циано-19 28-эпокси-18 -олеан-3-овой кислоты с первичными аминами, синтетическими и биогенными аминокислотами. Среди синтезированных азотсодержащих производных выявлен цитотоксичный тритерпеновый конъюгат с остатком этилового эфира -аланина, при 100 мкM-концентрации которого в среде выживаемость клеток меланомы составила 45.5%.

Novel 2,3-seco-triterpenic amides were prepared by the interaction of the chloride of 2,3-seco-l-cyano-19beta,28-epoxy-18alpha-oleane-3-oic acid with primary amines and synthetic and biogenic amino acids. A cytotoxic triterpenic conjugate with a residue of the ethyl ester of beta-alanine was found among the synthesized nitrogen-containing derivatives. Treatment with this conjugate in a concentration of 100 muM resulted in the 45.5% survival of melanoma cells in the medium.

Novel 2,3-seco-triterpenic amides were prepared by the interaction of the chloride of 1-cyano-19β,28-epoxy-18α-oleane-3-oic acid with primary amines and synthetic and biogenic amino acids. A cytotoxic triterpenic conjugate with a residue of the ethyl ester of β-alanine was found among the synthesized nitrogen-containing derivatives. Treatment with this conjugate in a concentration of 100 μM resulted in the 45.5% survival of melanoma cells in the medium.

Previously unknown amino-derivatives of the natural sesquiterpene lactone α -santonin were synthesized. The activity of the products against several human tumor-cell lines was studied.

The paper presents the basic directions of using the Databank on antineoplastic substances and, in particular, its basic partelectronic Database as a component of modern information technologies in the system of searching for new antineoplastic medicines.