SYNTHESIS, STRUCTURE, ANTIMICROBIAL AND ANTIFUNGAL ACTIVITIES OF DIACYLHYDRAZINES OF THIETHANYLPYRIMIDINE-2,4(1H,3H)-DIONE SERIES

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Issue: 
1
Year: 
2017

S.A. Meshcheryakova
Dr.Sc. (Pharm.), Associate Professor, Bashkir State Medical University (Ufa)
E-mail: svetlanama@mail.ru
V.A. Kataev
Dr.Sc. (Pharm.), Associate Professor, Bashkir State Medical University (Ufa)
D.A. Munasipova
Ph.D. (Chem.), Bashkir State Medical University (Ufa)
A.V. Shumadalova
Post-graduate Student, Bashkir State Medical University (Ufa)
A.K. Bulgakov
Dr.Sc. (Med.), Professor, Bashkir State Medical University (Ufa)

The aim is the synthesis of acyl derivatives on the basis of 2-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1- yl)acetohydrazides containing thiethane- and thiethane-1,1-dioxide, and research of antimicrobial and antifungal activities of the synthesized compounds. 2-[6-Methyl-2,4-dioxo-3-(thiethane-3-yl)-1,2,3,4-tetrahydro-1-yl]acetic acid is obtained and 2-[3-(1,1-dioxothiethan-3-yl)-6- methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-yl]acetic acid hydrazides are synthesized by hydrazinolysis of corresponding ethyl acetates. N'-acyl derivatives are synthesized by acylation of thiethane- and thiethane-1,1-dioxide containing 2-(6-methyl-2,4-dioxo- 1,2,3,4-tetrahydropyrimidine-1-yl)acetohydrazides with anhydrides and acid chlorides. Identity and the structure of synthesized compounds were identified by thin-layer chromatography, NMR spectra, elemental analysis date. Spatial forms of N,N'-diacylhydrazines are installed using methods NOESY and ROESY 2D NMR. Antimicrobial and antifungal activities of the synthesized compounds were determined by methods "diffusion in agar" and 10-fold dilution series on meat-broth (pH 7.2-7.4). As a result of researches it is established that N,N'-diacylhydrazines are superior to Streptocide action 10 times, and N,N'-diacylhydrazines showed comparable antimicrobial activity with Streptocide against St. aureus. N,N'-diacylhydrazines showed antifungalactivity against C. albicans equal Pimafucin and some N,N'-diacylhydrazines were more active than Pimafucin 10 times. Based on these data it is revealed some connection between the structure of N,N'-diacylhydrazines containing thiethanyl- and dioxothiethanylpyrimidine fragments and their activity. Increasing of oxidation degree of the sulfur atom in thiethane cycle leads to expansion of the antibacterial activity spectrum and increase the antifungal activity of the compounds. However, in the series of N,N'-diacylhydrazines containing the propionic anhydride residue, there is an inverse relationship: oxidation of thiethane cycle to 1,1-dioxide reduces antimycobacterial activity

Keywords: 
Key words: thiethane; thiethane-1
1-dioxide; pyrimidine-2
4 (1H
3H)-dione; acetohydrazide; N
N'-diacylhydrazines; E
Zisomerism; antimicrobial and antifungal activities.

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