The mechanism of action and modified synthesis of hydroxyurea


  • O. G. Demchuk Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine
  • M. R. Hrytsyna Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine https://orcid.org/0000-0002-9254-6590
  • L. O. Kobryn Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine
  • M. B. Kalytovska Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine
  • B. V. Gutyj Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine https://orcid.org/0000-0002-5971-8776
Keywords: hydroxyurea, hydroxycarbamide, colour reactions, qualitative analyses, quality control

Abstract

Searching of new drugs with antimitotic characteristics which can be used for decreasing of cancer cells dividing is the important issue of nowadays. One of such substances there is a hydroxyurea (HU) that is known as mitotical poison, because of characteristic to block a cellular cycle and as the specific inhibitor of DNA synthesis. It blocks the transition of cells from G1 – in S-phase. HU is a cytostatic agent with antineoplastic activity and presents great clinical efficiency in the treatment of sickle cell disease. HU and its derivatives exhibit versatile biological activities. HU is currently used in the treatment of various neoplastic and non-neoplastic diseases such as cancer, sickle cell anemia and HIV.Currently anticancer drugs are available that significantly reduce the mortality rates for some cancers (e.g. leukemia and testicular and ovarian cancer), and give longer overall patient survival times. In order to drug belongs to the pharmacotherapeutic group – antineoplastic agents and widely used for myelogenous leukemia, essential thrombocythemia treatment, our research was concerning the literature review on the ways and mechanisms of action of HU in living organisms. The ways and mechanisms of HU action in living organisms, research of antiviral and antimicrobial action of HU, the mechanism of HU influence at the cellular level and in antitumor and anticancer therapy have been studied. Under studying of radioprotector properties of hydroxyurea was established, that its efficiency is estimated by the values FCD (Factor of change of dose) within the limits of 1.2–1.4 – (to the peas 1.4 and corn – 1.3). A factor of change of dose is a relation of effective dose at the irradiation of organism with a radioprotector to the effective dose that predetermines the same radio-biology effect in control without a radioprotector. It was established that compounds with sulfurhydryl bonding possess the most radioprotective properties. It is considered that they have strong reduction properties and can be used as spin trapping of free radicals, shutting them out before binding with macromoleculas occurs, in particular to DNA. In order to obtain a sufficient amount of the drug hydroxyurea for analytical and pharmacological research, a modified method of it synthesis has been developed and proposed. The optimized synthesis conditions include conducting the experiment at lower temperatures -15 °C (wise -10 °C lit.), neutralization of the reaction mixture with concentrated 50 % sulfuric acid (wise dilute sulfuric acid, lit.); providing concentrated solution by reducing the total amount of water in the reaction 300 ml (wise 500 ml); evaporation and the filtration at room temperature by air flow (wise evaporation in vacuum at 40 °C, lit.); replacement of the solvent for extraction with butanol ( wise alcohol, lit.). Such conditions provided complete dissolution of urethane after 1 h and allow to receive the hydroxyurea pure enough, without further recrystallization. The target product was obtained with a higher yield (up to 91 %) and achieved simplicity and one-step method. The less toxic and cost-effective starting reagents were also used to reduce the cost of the synthesis process.

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Published
2020-12-23
How to Cite
Demchuk, O., Hrytsyna, M., Kobryn, L., Kalytovska, M., & Gutyj, B. (2020). The mechanism of action and modified synthesis of hydroxyurea. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences, 22(100), 60-65. https://doi.org/10.32718/nvlvet10011

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