Crimean State Medical University

Simferopol’, Ukraine

Crimean State Medical University

Simferopol’, Ukraine
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Nosulenko I.S.,Zaporizhzhia State Medical University | Voskoboynik Y.U.,Zaporizhzhia State Medical University | Berest G.G.,Post University | Safronyuk S.L.,Crimean State Medical University | And 5 more authors.
Scientia Pharmaceutica | Year: 2014

Potassium 8-R1-9-R2-10-R3-3-R-2-oxo-2Н-[1,2,4]triazino [2,3-с]quinazoline-6- thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R1-4-R2- 5-R3-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1-2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R1-4-R2-5-R3-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods (1H,13C NMR, LC-MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 µg/mL, MBC 12.5-200 µg/mL) to the synthesized compounds. © Nosulenko et al.


Berest G.G.,Zaporozhye State Medical University | Voskoboynik O.Y.,Zaporozhye State Medical University | Kovalenko S.I.,Zaporozhye State Medical University | Nosulenko I.S.,Zaporozhye State Medical University | And 4 more authors.
Scientia Pharmaceutica | Year: 2012

Several novel 6-thio-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-based com-pounds containing an ω-(dialkylamino(heterocyclyl)]alkyl fragment were synthe-sized to examine their anticancer activity. Some of the 6-{[ω-(hetero-cyclyl)alkyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.1-3.10) were obtained by the nucleophilic substitution of 6-[ω-halogenalkyl]thio-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (2.1-2.8) with azaheterocycles. Alter-natively, compounds 3.1-3.22 were synthesized by alkylation of 3-R-6-thio-2N{cyrillic}-[1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts (1.1-1.4) with (2-chloro-ethyl)-N,N-dialkylamine hydrochlorides or 1-(2-chloroethyl)heterocycle hydro-chlorides. The structures of compounds were elucidated by 1H, 13C NMR, LC-MS and EI-MS analysis. Then anticancer and antibacterial, biolumi-nescence inhibition of Photobacterium leiognathi Sh1 activities of the sub-stances were tested in vitro. It was found that compound 3.18 possessed a wide range of anticancer activity against 27 cell lines of cancer: non-small cell lung, colon, CNS, ovarian, renal, prostate, breast, melanoma and leukemia (log GI 50 < - 5.65). The "structure-activity" relationship was discussed. COMPARE analysis for synthesized anticancer active compounds was performed.© Berest et al.


Kovalenko S.I.,Zaporozhye State Medical University | Nosulenko I.S.,Zaporozhye State Medical University | Alexey Y.,Zaporozhye State Medical University | Berest G.G.,Zaporozhye State Medical University | And 3 more authors.
Scientia Pharmaceutica | Year: 2012

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1-1.4 by N-hetaryl-2-chloro-acetamides and by aminolysis of activated acids 2.1-2.4 with N,N'-carbonyl-diimidazole (CDI). The structures of compounds were determined by IR, 1H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bio-luminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI50 at 0.41-0.69 μM{cyrillic}), melanoma (GI50 0.48-13.50 μM), and ovarian cancer (GI50 0.25-5.01 μM). The structure-activity relationship (SAR-analysis) was discussed. © Kovalenko et al.


Efetov K.A.,Crimean State Medical University | Parshkova E.V.,Crimean State Medical University | Baevsky M.Y.,Taurida National University | Poddubov A.I.,Taurida National University
Ukrain'skyi Biokhimichnyi Zhurnal | Year: 2014

2-butyl 2-dodecenoate has been synthesized from lauric acid and sec-butanol. The study of the biological activity of this substance has demonstrated its property as a sex attractant for males of Jordanita graeca, Jordanita globulariae and Theresimima ampellophaga (Lepidoptera: Zygaenidae, Procridinae). The latter species is the grape pest in southern Europe. The attractant obtained can be used for the detection of species, for monitoring their numbers in nature and for the elaboration of ecological methods of pest control.


Taran M.V.,National University of Life and Environmental Sciences of Ukraine | Starodub N.F.,National University of Life and Environmental Sciences of Ukraine | Katsev A.M.,Crimean State Medical University | Guidotti M.,National Research Council Italy | And 3 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2013

The effect of silver and zinc oxide nanoparticles in combination with alginate on bioluminescent Photobacterium leiognathi Sh1 bacteria was investigated. Silver nanoparticles were found to be more toxic than zinc oxide nanoparticles on bioluminescent bacteria. The nanoparticles and their ions released results in the same effect, however, it was absent in combination with alginate. The effective inhibiting concentration (EC50) for silver nanoparticles was found about 0.3 - 0.4 μg mL-1, which was up to two times larger then for zinc oxide nanoparticles. The absence of sodium chloride in the tested media prevented the formation of colloidal particles of larger size and the effective inhibition concentrations of metal derivatives were lower than in the presence of sodium chloride. © 2013 SPIE.


Knyazev S.A.,KV Inc | Efetov K.A.,Crimean State Medical University | Ponomaryov K.B.,KV Inc
Entomological Review | Year: 2015

The fauna of the family Zygaenidae of Omsk Province is reviewed. 12 species are listed, among which 7 are recorded from this territory for the first time. © 2015, Pleiades Publishing, Inc.


Fleishaker D.L.,Pfizer | Garcia Meijide J.A.,Hospital Ntra Sra Of La Esperanza | Petrov A.,Crimean State Medical University | Kohen M.D.,Avivoclin Clinical Services | And 7 more authors.
Arthritis Research and Therapy | Year: 2012

Introduction: The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).Methods: This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.Results: Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).Conclusions: Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.Trial Registration: ClinicalTrials.gov: NCT00427934. © 2011 Fleishaker et al.; licensee BioMed Central Ltd.


PubMed | Zaporizhzhia State Medical University, Post University and Crimean State Medical University
Type: Journal Article | Journal: Scientia pharmaceutica | Year: 2015

Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1-2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 g/mL, MBC 12.5-200 g/mL) to the synthesized compounds.


Berest G.G.,Zaporozhye State Medical University | Voskoboynik O.Y.,Zaporozhye State Medical University | Kovalenko S.I.,Zaporozhye State Medical University | Antypenko O.M.,Zaporozhye State Medical University | And 3 more authors.
European Journal of Medicinal Chemistry | Year: 2011

In this paper the novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H-[1, 2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides synthesis by aminolysis of activated by thionyl chloride or carbonyldiimidazole [(3-R-2-oxo-2H-[1,2,4] triazino[2,3-c]quinazolin-6-yl)-thio]acetic acids and alkylation of the 3-R-6-thio-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts with N-cycloalkyl-(cycloalkylaryl)-2-chloroacetamides are proposed. The structures of compounds are determined by 1H, 13C NMR, LC-MS and EI-MS analysis. The in vitro anticancer, antibacterial activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds were revealed. SAR results were discussed. Compound 4.10 was found to be the most anticancer active one, selectively influenced on the non-small cell lung and CNS cancer cell lines, especially on the HOP-92 (log GI50 = -6.01) and U251 (log GI50 = -6.00). © 2011 Elsevier Masson SAS. All rights reserved.


Kovalenko S.I.,Zaporozhye State Medical University | Nosulenko I.S.,Zaporozhye State Medical University | Voskoboynik A.Yu.,Zaporozhye State Medical University | Berest G.G.,Zaporozhye State Medical University | And 3 more authors.
Medicinal Chemistry Research | Year: 2013

The series of novel N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c] quinazoline-6-yl)thio]acetamides were obtained by aminolysis of activated acids 1a-1d and by alkylation of potassium salts 2a-2d by N -aryl-2-chloroacetamies. The structures of compounds were determined by IR, 1H, 13C NMR, LC- and EI-MS analyses. The results of cytotoxicity evaluation by bioluminescence inhibition of bacterium Photobacterium leiognathi Sh1 showed that compounds reveal moderate cytotoxicity. Screening of anticancer activity in vitro yielded the most active compounds 3t, 4b, 4f, 4l and 4n in micromolar concentrations with the GI50 level (logGI50 is from -7.57 to -4.05 for different cell lines, and logGI50 mean graph midpoint varied from -5.30 to -4.50). Moreover, compound 4b had a distinctive selectivity against renal cancer, 4f - colon cancer and melanoma and 4l - renal cancer. The highest sensitivity to compound 4b showed renal cancer cell lines A498 (logGI50 = -7.57). SAR-analysis was discussed, COMPARE analysis and docking was studied. Graphical Abstract: The novel synthesis methods of the N-aryl(alkaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio] acetamides are proposed. Anticancer activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds are discussed. SAR-analysis was discussed, and COMPARE analysis and docking was studied. © 2012 Springer Science+Business Media New York.

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