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.
As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.
Nanozymes, which have high enzyme-like activity of natural enzymes, are very promising for analytical purposes, in particular, for the development of methods for sensitive, quantitative detection of practically important analytes – biomarkers of common diseases or pharmaceutical products. Recently, it has been reported that artificial enzymes with laccase-like activity or “nanolaccases (nLacs),” can serve as catalytic elements for the creation of sensitive methods for catecholamines. Our work aimed to obtain laccase-like nanozymes and characterize and demonstrate their suitability for spectrophotometric adrenaline (AD) analysis. In this article, we report on preparing five hexacyanoferrate nanoparticles (HCF NPs) that possess laccase-like activity, particularly, Co-HCF, Ni-HCF, Mn-HCF, Zn-HCF, and Cu-HCF. Among the investigated nLacs, Cu-HCF was selected and characterized. It was shown that Cu-HCF reveals the highest activities, is stable in various pH conditions in the range 3.0–6.5, and has satisfactory stored stability. A new spectrophotometric method for the quantitative detection of AD was created using the selected nLacs. The linearity of the proposed method is in the range from 5 μM to 50 μM (0.66–11 μg/ml), and the limit of detection is 1.5 μM (0.33 μg/ml), which is lower than that catalyzed by native laccase (1.15 μg/ml). The proposed method was tested on the real samples of pharmaceuticals, and the obtained data agree with the data declared by the producer. The resulting nLacs have great potential for use in catalysis of mimetics, environmental restoration, and sensor design. Thus methods, the obtained Cu-HCF has great potential application in spectrophotometric and biosensor method for analysis of biologically active toxic compounds in surface waters.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.