Abstract
Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research.
Highlights
The incidence of cancer remains common in spite of the discoveries in the field of tumor cells, molecular biology, and a variety of surgical, radiation, and pharmacological intervention methods on various stages and components of tumor growth, which is why it is important to create effective anticancer drugs and improve existing therapies [1]
From the results of several preliminary preclinical trials, it was established that, by single intravenous medication administration, ormustine in a 125 mg/kg dose led to the successful treatment of mice with leukoses in a large percentage of cases
In regard to P-388 lymphocytic leukemia, ormustine led to the treatment of mice in 50% of cases; in regard to L-1210 lymphoid leukemia, it was 66.7%; in regard to the cervical cancer (CC), ormustine led to the treatment of all mice in the experimental group
Summary
The incidence of cancer remains common in spite of the discoveries in the field of tumor cells, molecular biology, and a variety of surgical, radiation, and pharmacological intervention methods on various stages and components of tumor growth, which is why it is important to create effective anticancer drugs and improve existing therapies [1]. There is an ongoing search for original drug substances (DS), which is based on carrying out chemical, physical, biological, and pharmaceutical studies [2]. One of the priority directions of research in this area is the development of new anticancer drugs derived from nitrosoureas (NUs) that belong to alkylating agents. InofpOrerlgimaninicarSyybnitohleosgiiscahl aesxploecriamllyenstsyncathrreiseidzeodutainnethwe Fsuedbesrtaanl cSetatferoBmutdhgeetNarUy Sclcaiessn—tifoicrmInusstittiuntei.onIn, tphreeNlim.Nin. aBrlyokbhioinloRguicsasliaenxpCearnimceernRtsesceaarrrciehdCoeuntteinr, tiht ewFaesdfoeuranldSttahtaet Bourmdguesttainrye iSncdieuncteifis cthInesdtietuattihono,fthtuemNo.Nr .ceBllloskbhyinthReusmsieacnhCanainscmeroRfeeseaarlrychaCpoenptteors,isit; wmaosrfeoouvnedr, tohnataonrimmuaslsti,niet einxdhuibcietss thhieghdedaothseo-df teupmenodrecnetllasnbtyittuhme omreacchtaivniitsym[7o–f1e0a]r.ly apoptosis; on animals, it exhibits high Tdhouses-,dthepeecnrdeaetnitonanotiftuamstoarbalectaivnidtye[f7fe–c1t0iv].e pharmaceutical composition (PF) of ormustine is a highlTyhruesle, vtahnetcarreeaatioofnreosfeaarsctha.ble and effective pharmaceutical composition (PF) of ormustine is a highly relevant area of research
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