Background. The purpose of this investigation is the search of new compounds with high selectivity of antitumor action on the tumor of the gastrointestinal tract (GIT) in the series of analogues of the peptide hormone gastrin. Objective: synthesis of 2 analogues of gastrin, 1 of which contains the cytotoxic group, the study of their cytotoxic and antitumor activity. Materials and methods. Synthesis of peptides was carried out by classical methods of peptide chemistry. Cytotoxic activity was studied on the cell culture НСТ116. Antitumor activity of analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. Results. Two analogues of gastrin (octapeptide) were synthesized, 1 of which contains a cytotoxic group. Analogue containing cytotoxic group revealed the cytotoxic activity. Antitumor activity of two analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. The cytotoxic and non-cytotoxic analogues of gastrin showed antitumor activity only on AKATON. Inhibition of tumor growth is 74 and 84 %, respectively. Conclusions. The therapeutic effect of two analogues of gastrin on adenocarcinome AKATON, probably, is associated with the expression of gastrin receptors ССК2 in this tumor.

Background. The drug cyphetrylin, hypothalamic hormone somatostatin analogue, was developed in N.N. Blokhin Russian Cancer Research Center at the Ministry of Health of Russia. The basis of this work is the idea of using cyphetrylin as a specific carrier of cytotoxic groups. Objective. Synthesis of cytotoxic cyphetrylin analogues in order to study the effect of the presence of cytotoxic agents on its antitumor activity. Results. The classical methods of peptide chemistry were used for 5 the new cyphetrylin analogues synthesis. The compounds have been obtained by the addition to the cyphetrylin Na-group of the cysteine or lysine Ns-group chlorophenacyl or hydrolyzed сyphelin (cytotoxic agent). Purification of the peptides was performed by column chromatography on silica gel. The purity of the obtained compounds was confirmed by elemental analysis, TLC, optical rotation angle data and HPLC. Preliminary studies of anti-tumor activity were performed in mice transplanted tumors: adenocarcinoma Ca755 breast and melanoma B16. Conclusions. New peptides - analogues cyphetrylin containing cytotoxic fragment have been synthesized, their structure and purity have been confirmed.

Background. In N.N. Blokhin Russian Cancer Research Center have been synthesized a number of hypothalamic hormone somatostatin analogues, including pentapeptide cyphetrylin, and drug Cyphetrylin tablets 6 mg has been created. One of the drug standardization step is development of assay technique for acting substance in the final preparation. Objective. Development and validation of cyphetrylin assay in tablets. Materials and methods. The study used cyphetrylin, tablets 6 mg, сyphetrylin powder substance (FSBI “N.N. Blokhin Russian Cancer Research Center”, branch “Naukaprofi”), lactose monohydrate, cellulose microcrystalline, potato starch, povidone, talc, magnesium stearate (European Pharmacopoeia current edition), 95 % ethyl alcohol. Method of assay spectrophotometry. Results. The technique for assay of сyphetrylin in drug “Cyphetrylin, tablets 6 mg” has been developed. Validation was performed to confirm test validity and accuracy. The technique was estimated by validation characteristics: specificity, linearity, accuracy, precision (repeatability and intermediate precision). Conclusion. The developed technique has the required characteristics: specificity, accuracy, repeatability, intermediate precision, linearity and can be used in the range of 70-130 % of nominal сyphetrylin content in preparation.

Background. In N.N. Blokhin Russian Cancer Research Center have been synthesized a number of hypothalamic hormone somatostatin analogues, including pentapeptide cyphetrylin, and drug Cyphetrylin tablets 6 mg has been created. One of the drug standardization step is development of assay technique for acting substance in the final preparation. Objective. Development and validation of cyphetrylin assay in tablets. Materials and methods. The study used cyphetrylin, tablets 6 mg, сyphetrylin powder substance (FSBI “N.N. Blokhin Russian Cancer Research Center”, branch “Naukaprofi”), lactose monohydrate, cellulose microcrystalline, potato starch, povidone, talc, magnesium stearate (European Pharmacopoeia current edition), 95 % ethyl alcohol. Method of assay - spectrophotometry. Results. The technique for assay of сyphetrylin in drug “Cyphetrylin, tablets 6 mg” has been developed. Validation was performed to confirm test validity and accuracy. The technique was estimated by validation characteristics: specificity, linearity, accuracy, precision (repeatability and intermediate precision). Conclusion. The developed technique has the required characteristics: specificity, accuracy, repeatability, intermediate precision, linearity and can be used in the range of 70-130 % of nominal сyphetrylin content in preparation.

An analog of somatostatin with hormonal and antitumor activity was synthesized. An optimum synthesis method was developed, yielding standard pharmaceutical somatostatin analog substance for preclinical and clinical studies. A quality control method was developed for inclusion in the draft manufacturer’s pharmacopeia monograph for pharmacological somatostatin analog substance.

Синтезирован аналог соматостатина, обладающий гормональной и противоопухолевой активностью. Разработан оптимальный метод синтеза, позволяющий получать стандартную фармацевтическую субстанцию аналога соматостатина для доклинических и клинических исследований. Разработаны методики контроля качества, которые будут включены в проект ФСП на фармацевтическую субстанцию аналога соматостатина.

Investigated the antitumor activity of synthetic peptide somatostatin agonists on models of transplanted tumors in mice: cervical cancer, Lewis lung epidermoid carcinoma and mammary adenocarcinoma (Ca-755) as in the ordinary and in the long-acting forms.

Some somatostatine analogs were synthesized and tested for cytotoxic activity in comparison with sandostatine and octreotide in cell cultures, expressing somatostatine receptors: human prostate carcinoma cell line LNCap, LNCap-LN3, LNCap-clon FGC and human neuroblastoma cell line SH-SY5Y.

Hormonal and antitumour activities of 4 somatostatin hypothalamic hormone analogues were investigated. It has been showed that the compounds partially retain their specific somatostatin hormonal activity, and this was appeared in secretion inhibition of somatotrophic hormone, prolactin and insulin by corresponding endocrine glands in vitro and in vivo. It has been established that the compounds inhibit the growth of adenocarcinoma prostate of rats R-3327-H, DMBA induced breast tumours of rats and compounds I and II of breast tumor PM-1 in nude mice, exceeding antitumour action of sandostatine. The compounds I and II are the most active analogues.