The antitumor potential of a new original compound T1097 to realize a complex antineoblastic effect - NOS-inhibiting anti-angiogenic and HK2-inhibiting hypoxia-oriented cytotoxic - was investigated on the model of transplantable Ehrlich carcinoma in vivo. During the entire observation period, T1097 showed pronounced dose-dependent antitumor properties: statistically significant inhibitory effect of T1097 on the growth of tumor nodes exceeded the effect of original compound - HK2-inhibitor 3-bromopyruvate in an equimolar dose. The maximum antineoblastic effect (61%) of T1097 was obtained with its subchronic parenteral administration at a dose of 17 mg/kg and was not accompanied by the development of tumor resistance. Our findings confirm the prospects of this direction in the search for new drugs.

Polymeric palladium complexes [(C5H12NO)(PdCl3)]n (I) and [(C10H16NO)2(Pd2Cl6)] (II) were synthesized for the first time and studied by X-ray diffraction. Complexes I and II were found to have moderate toxicity (3rd class of toxicity) and high antitumor and radioprotective activities. Treatment of Lewis lung carcinoma (LLC) with I and II induced statistically significant antitumor and antimetastatic effects exceeding those of cisplatin: the use of I and II retarded the growth of LLC by 60.0%, while cisplatin retarded it by 48.0%. The decrease in the LLC metastasis was 75% upon the action of I, 91.0% in the case of II, and 69.0% for cisplatin. It was shown that II has a clear-cut radioprotective action. On single exposure of mice to a dose of 8.2 Gy, their survival rate was 58.0% versus 4.5% for the control. Fractional exposure to increasing doses (2.5, 3, and 3.5 Gy) resulted in 75.0% survival rate versus 33.0% for the control.

Polymeric palladium complexes [(C 5 H 12 NO)(PdCl 3 )] n ( I ) and [(C 10 H 16 NO) 2 (Pd 2 Cl 6 )] ( II ) were synthesized for the first time and studied by X-ray diffraction. Complexes I and II were found to have moderate toxicity (3rd class of toxicity) and high antitumor and radioprotective activities. Treatment of Lewis lung carcinoma (LLC) with I and II induced statistically significant antitumor and antimetastatic effects exceeding those of cisplatin: the use of I and II retarded the growth of LLC by 60.0%, while cisplatin retarded it by 48.0%. The decrease in the LLC metastasis was 75% upon the action of I , 91.0% in the case of II , and 69.0% for cisplatin. It was shown that II has a clear-cut radioprotective action. On single exposure of mice to a dose of 8.2 Gy, their survival rate was 58.0% versus 4.5% for the control. Fractional exposure to increasing doses (2.5, 3, and 3.5 Gy) resulted in 75.0% survival rate versus 33.0% for the control.

Combined chronic treatment of Ehrlich solid carcinoma (EC) with an NOS inhibitor 1-isobutanoyl-2-isopropylisothiourea hydrobromide (T1023) and a PDK1 inhibitor dichloroacetate was accompanied by statistically significant synergetic antitumor effects manifested in a significant and stable suppression of neoplasm growth (by 55-65%). Separate treatment with T1023 and dichloroacetate induced moderate short-term inhibition of tumor growth (by 30-35%) followed by weakening of tumor sensitivity to these substances. These results attest to synergetic antitumor effects NOS inhibitor T1023 and PDK1 inhibitor dichloroacetate producing antiangiogenic and hypoxia-targeted cytotoxic effects, during their combined administration, which allows overcoming the adaptive potential of the tumors.