5 research outputs found
IR and UV-VIS spectroscopic analysis of a new compound: N-[1-(4-hydroxyphenyl) aminoethilyden]-4-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphtalen-2-yl)-ethenyl] phenylcarbohydrazide
INTRODUCTION: Hydrazones are compounds that can be considered as hydrogenated azo compounds or as derivatives of hydrazine (H2N-NH2) in the structure of which one hydrogen atom at each nitrogen is replaced by a hydrocarbon group. In this work, we discuss the possibilities for analysis of a newly synthesized hydrazone of the retinoid bexarotene with acetaminophen using infrared (IR) and ultraviolet-visible (UV-VIS) spectroscopy.Β Β AIM: The purpose of this study is to perform Fourier-transfrom infrared (FTIR) and UV-VIS spectroscopic analysis of a newly synthesized hydrazone of bexarotene.Β MATERIALS AND METHODS: Π newly synthesized hydrazone derivative was obtained according to the basic scheme of synthesis of bexarotene analogs. Infrared spectra 500-4000 cm-1 were taken on a Bruker FTIR spectrometer using ATRβa plug with a Smart iTR adapter. Spectra in the range 190β325 nm were recorded using UV-VIS spectrophotometer T60 UV with UVWin Software 6.0.Β RESULTS: After a detailed comparison of the data obtained in the IR analysis of the reagents and the newly obtained hydrazone, a similar position and intensity of the spectral bands are reported. However, there are displacements in spectral bands and significant differences corresponding to the structural changes that have occurred. Different values for the wavelength of maximum absorption were measured with a UV-VIS spectrophotometer for bexarotene, Paracetamol, and the newly synthesized compound.Β CONCLUSION: In order to confirm the data obtained by FTIR and UV-VIS spectroscopy, a further reversed-phase high-performance liquid chromatography-ultraviolet (HPLC-UV) analysis of the new hydrazone derivative should be performed
FT-IR spectral analysis for a newly obtained structure analog of bexarotene
INTRODUCTION: Retinoids are natural and synthetic compounds part of the family of polyisoprenoid lipids. These compounds are involved in several important physiological processes in the human body because of their ability to bind to different nuclear receptors. Retinoids are used in the therapy of some precancerous lesions, the treatment of acute promyelocytic leukemia (APL), T-cell lymphoma, and the prevention of malignancies in high-risk cancer groups. In this work we discuss the possibilities for analysis of the newly synthesized hydrazone of the retinoid bexarotene. Β AIM: The purpose of this study is to conduct FTIR spectral analysis of newly synthesized hydrazone of bexarotene.MATERIALS AND METHODS: Infrared spectra 500-4000 cm-1 were taken on a Bruker FTIR spectrometer using ATR - a plug with Smart iTR adapter.RESULTS: The infrared spectra of the newly synthesized compound were strikingly similar in the relative positions and intensities of the resulting peaks, confirming its close structural relationship with bexarotene. Despite the structural similarity, there were significant differences that point to the introduction of a substituent and the formation of a new hydrazone derivative.CONCLUSION: Β In order to confirm the data obtained by FTIR spectroscopy, a further reversed-phase HPLC-UV analysis of the new hydrazone derivative should be performed
Antibacterial activity of 4-isopropyl-phenyl-methylidene-4- [1- (3,5,5,8,8-pentamethyl-6,7-dihydronaphthal-2-yl) ethenyl] benzohydrazyde
The increase in antibiotic resistance of microorganisms encourages the constant search for new compounds. Studies on the activity of hydrazones identify them as promising compounds for further microbiological research. The aim of the present study is to determine the antibacterial activity of newly synthesized 4-isopropyl-phenyl-methylidene-4- [1- (3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl) ethe- nyl] benzohydrazide, an analog of the antineoplastic preparation bexarotene. The assay was performed against clinical isolates of Escherichia coli and Staphylococcus aureus
Synthesis and Characterization of Bexarotene Derivatives with Potential Biological Activity // ΠΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ ΠΈ ΠΎΡ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΠ°Π½Π΅ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ΠΎΠ²ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ Ρ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π½Π° Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡ
The dissertation deals with the preparation and characterization of the newly synthesized derivatives of the synthetic retinoid bexarotene. The continued and intensive study of the role of retinoids in the complex of differentiation, cell proliferation, and cellular growth processes determines the major potential for the using of retinoids (natural and synthetic) in the treatment of a number of abnormalities arising from abnormal cell development. Of particular interest is the possibility of their use in the treatment of neoplastic processes in the body.
Bexarotene is a third-generation retinoid and is used in the treatment of T-cell skin cancer. In addition to its proven application in oncology, there are a number of data on the effects of neurological and autoimmune processes in the body.
For the preparation of bexarotene derivatives, a three-step synthetic scheme has been developed. Involving the preparation of hydrazide and the subsequent interplay with carbonyl compounds to form the target hydrazones. Hydrazide-hydrazone compounds have attention in the last few decades because of the diverse pharmacological effects they possess. Hydrazones and their derivatives are known to exhibit a wide range of pharmacological effects such as antioxidant, anti-inflammatory, analgesic, antimicrobial, anthelmintic, anti-tuberculosis, etc. The development of the hydrazone class of compounds has made significant progress and many new aspects of application have been discovered.
The resulting hydrazide hydrazones have been characterized structurally by instrumental methods including the use of infrared spectroscopy, 1H-NMR spectroscopy, and mass spectrometry. A validated HPLC method for the determination of bexarotene and its derivatives alone and in mixtures has been successfully applied.
The antioxidant potential of the newly obtained bexarotene derivatives was evaluated using three different approaches - electron transfer capability - ABTS test, hydrogen atom transfer-DPPH test, as well as an electrochemical pathway.
With the help of theoretical approaches, the possibilities for metabolic activation of bexarotene have been successfully identified, also its metabolites and new derivatives evaluated. The mechanisms by which the metabolites of the newly prepared compounds can potentiate liver damage through specific interactions with biological macromolecules (DNA and proteins) in the liver have been identified and summarized. The possibility of producing dermal metabolites has also been determined. // [BG] ΠΠΈΡΠ΅ΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΈΡ ΡΡΡΠ΄ ΡΠ°Π·Π³Π»Π΅ΠΆΠ΄Π° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ΡΠΎ ΠΈ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΠ°Π½Π΅ΡΠΎ Π½Π° Π½ΠΎΠ²ΠΎΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠ°Π½ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ Π½Π° ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½ΠΈΡ ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½. ΠΡΠΎΠ΄ΡΠ»ΠΆΠ°Π²Π°ΡΠΎΡΠΎ ΠΈ ΠΈΠ½ΡΠ΅Π½Π·ΠΈΠ²Π½ΠΎ ΠΈΠ·ΡΡΠ°Π²Π°Π½Π΅ Π½Π° ΡΠΎΠ»ΡΡΠ° Π½Π° ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈΡΠ΅ Π² ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° ΠΎΡ ΠΏΡΠΎΡΠ΅ΡΠΈ Π½Π° Π΄ΠΈΡΠ΅ΡΠ΅Π½ΡΠΈΠ°ΡΠΈΡ, ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ ΠΈ ΡΠ΅Π³ΡΠ»Π°ΡΠΈΡ Π½Π° ΠΊΠ»Π΅ΡΡΡΠ½ΠΈΡ ΡΠ°ΡΡΠ΅ΠΆ ΠΎΠ±ΡΡΠ»Π°Π²Ρ Π³ΠΎΠ»Π΅ΠΌΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» Π·Π° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π½Π° ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈ (Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½ΠΈ ΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½ΠΈ) ΠΏΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΠ΅ΡΠΎ Π½Π° ΡΠ΅Π΄ΠΈΡΠ° Π½Π°ΡΡΡΠ΅Π½ΠΈΡ, ΠΏΡΠΎΠΈΠ·ΡΠΈΡΠ°ΡΠΈ ΠΎΡ Π°Π½ΠΎΡΠΌΠ°Π»Π½ΠΎΡΠΎ ΠΊΠ»Π΅ΡΡΡΠ½ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅. ΠΠ°ΡΠΎ Ρ ΠΎΡΠΎΠ±Π΅Π½ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΡΠ΅ ΡΠ°Π·Π³Π»Π΅ΠΆΠ΄Π° Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡΠ° Π·Π° ΡΠΏΠΎΡΡΠ΅Π±Π°ΡΠ° ΠΈΠΌ Π² ΡΠ΅ΡΠ°ΠΏΠΈΡΡΠ° Π½Π° Π½Π΅ΠΎΠΏΠ»Π°ΡΡΠΈΡΠ½ΠΈ ΠΏΡΠΎΡΠ΅ΡΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°.
ΠΠ΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ΡΡ ΡΠ΅ ΠΎΡΠ½Π°ΡΡ ΠΊΡΠΌ ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈΡΠ΅ ΠΎΡ ΡΡΠ΅ΡΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΠ΅ ΠΈ Π½Π°ΠΌΠΈΡΠ° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² ΡΠ΅ΡΠ°ΠΏΠΈΡΡΠ° Π½Π° Π’-ΠΊΠ»Π΅ΡΡΡΠ΅Π½ ΠΊΠΎΠΆΠ΅Π½ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌ. ΠΡΠ²Π΅Π½ ΡΡΠ²ΡΡΠ΄Π΅Π½ΠΎΡΠΎ ΡΠΈ ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΡΠ° ΡΠ΅Π΄ΠΈΡΠ° ΡΠ° Π΄Π°Π½Π½ΠΈΡΠ΅ Π·Π° Π΅ΡΠ΅ΠΊΡΠΈ ΠΏΡΠΈ Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ ΠΈ Π°Π²ΡΠΎΠΈΠΌΡΠ½Π½ΠΈ ΠΏΡΠΎΡΠ΅ΡΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°.
ΠΠ° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ Π΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ΅Π½Π° ΡΡΠΈΠ΅ΡΠ°ΠΏΠ½Π° ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½Π° ΡΡ
Π΅ΠΌΠ°, Π²ΠΊΠ»ΡΡΠ²Π°ΡΠ° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° Ρ
ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄ ΠΈ ΠΏΠΎΡΠ»Π΅Π΄Π²Π°ΡΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Ρ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»Π½ΠΈ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π΄ΠΎ ΡΠΎΡΠΌΠΈΡΠ°Π½Π΅ Π½Π° ΡΠ΅Π»Π΅Π²ΠΈΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈ. Π₯ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄-Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ²ΠΈΡΠ΅ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΏΡΠΈΠ²Π»ΠΈΡΠ°Ρ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ΡΠΎ ΠΏΡΠ΅Π· ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡΠ΅ Π½ΡΠΊΠΎΠ»ΠΊΠΎ Π΄Π΅ΡΠ΅ΡΠΈΠ»Π΅ΡΠΈΡ ΠΏΠΎΡΠ°Π΄ΠΈ ΡΠ°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·Π½ΠΈΡΠ΅ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ Π΅ΡΠ΅ΠΊΡΠΈ, ΠΊΠΎΠΈΡΠΎ ΠΏΡΠΈΡΠ΅ΠΆΠ°Π²Π°Ρ. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ Π΅, ΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈΡΠ΅ ΠΈ ΡΠ΅Ρ
Π½ΠΈΡΠ΅ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΠΏΡΠΎΡΠ²ΡΠ²Π°Ρ ΡΠΈΡΠΎΠΊ ΡΠΏΠ΅ΠΊΡΡΡ ΠΎΡ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ Π΅ΡΠ΅ΠΊΡΠΈ ΠΊΠ°ΡΠΎ Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ΅Π½, ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΡΠ·ΠΏΠ°Π»ΠΈΡΠ΅Π»Π΅Π½, Π°Π½Π°Π»Π³Π΅ΡΠΈΡΠ΅Π½, Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½Π΅Π½, Π°Π½ΡΠΈΡ
Π΅Π»ΠΌΠΈΠ½ΡΠ΅Π½, ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ±Π΅ΡΠΊΡΠ»ΠΎΠ·Π΅Π½ ΠΈ Ρ.Π½. Π Π°Π·Π²ΠΈΡΠΈΠ΅ΡΠΎ Π½Π° Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ²ΠΈΡ ΠΊΠ»Π°Ρ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π±Π΅Π»Π΅ΠΆΠΈ Π·Π½Π°ΡΠΈΡΠ΅Π»Π΅Π½ ΠΏΡΠΎΠ³ΡΠ΅Ρ ΠΈ ΡΠ΅ ΡΠ°Π·ΠΊΡΠΈΠ²Π°Ρ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²ΠΎ Π½ΠΎΠ²ΠΈ Π°ΡΠΏΠ΅ΠΊΡΠΈ Π½Π° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅.
ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄-Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈ ΡΠ° ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΠ°Π½ΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΠΎ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»Π½ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΈ Π²ΠΊΠ»ΡΡΠΈΡΠ΅Π»Π½ΠΎ ΠΏΡΠΈΠ»Π°Π³Π°Π½Π΅ Π½Π° ΠΈΠ½ΡΡΠ°ΡΠ΅ΡΠ²Π΅Π½Π° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΡ, 1Π-Π―ΠΠ -ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΡ ΠΈ ΠΌΠ°ΡΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡ. Π£ΡΠΏΠ΅ΡΠ½ΠΎ Π΅ ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ ΠΈ Π²Π°Π»ΠΈΠ΄ΠΈΡΠ°Π½ HPLC ΠΌΠ΅ΡΠΎΠ΄ Π·Π° ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ½Π΅ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ ΠΈ Π½Π΅Π³ΠΎΠ²ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΡΠ°ΠΌΠΎΡΡΠΎΡΡΠ΅Π»Π½ΠΎ ΠΈ Π² ΡΠΌΠ΅ΡΠΈ.
ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π° Π΅ ΠΎΡΠ΅Π½ΠΊΠ° Π½Π° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» Π½Π° Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ΠΎΠ²ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΡΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° β ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ Π·Π° Π΅Π»Π΅ΠΊΡΡΠΎΠ½Π΅Π½ ΠΏΡΠ΅Π½ΠΎΡ β ABTS-ΡΠ΅ΡΡ, ΠΏΡΠ΅Π½ΠΎΡ Π½Π° Π²ΠΎΠ΄ΠΎΡΠΎΠ΄Π΅Π½ Π°ΡΠΎΠΌ-DPPH-ΡΠ΅ΡΡ, ΠΊΠ°ΠΊΡΠΎ ΠΈ ΠΏΠΎ Π΅Π»Π΅ΠΊΡΡΠΎΡ
ΠΈΠΌΠΈΡΠ΅Π½ ΠΏΡΡ.
Π‘ ΠΏΠΎΠΌΠΎΡΡΠ° Π½Π° ΡΠ΅ΠΎΡΠ΅ΡΠΈΡΠ½ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΈ ΡΡΠΏΠ΅ΡΠ½ΠΎ ΡΠ° ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠ°Π½ΠΈ Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈΡΠ΅ Π·Π° ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ½ΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠ°Π½Π΅ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½, ΠΎΡΠ΅Π½Π΅Π½ΠΈ ΡΠ° Π½Π΅Π³ΠΎΠ²ΠΈΡΠ΅ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈ ΠΈ Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠ°Π½ΠΈ ΠΈ ΠΎΠ±ΠΎΠ±ΡΠ΅Π½ΠΈ ΡΠ° ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΈΡΠ΅, ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΊΠΎΠΈΡΠΎ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈΡΠ΅ Π½Π° Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΌΠΎΠ³Π°Ρ Π΄Π° ΠΏΠΎΡΠ΅Π½ΡΠΈΠΈΡΠ°Ρ ΡΠ΅ΡΠ½ΠΎΠ΄ΡΠΎΠ±Π½ΠΎ ΡΠ²ΡΠ΅ΠΆΠ΄Π°Π½Π΅, ΡΡΠ΅Π· ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΈ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π½Π° Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Ρ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈΡΠ΅ ΠΌΠ°ΠΊΡΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΠΈ (ΠΠΠ ΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΈ) Π² ΡΠ΅ΡΠ½ΠΈΡ Π΄ΡΠΎΠ±. Π‘ΡΡΠΎ ΡΠ°ΠΊΠ° Π΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° ΠΈ Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡΠ° Π·Π° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° Π΄Π΅ΡΠΌΠ°Π»Π½ΠΈ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈ.[BG] ΠΠΈΡΠ΅ΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΈΡ ΡΡΡΠ΄ ΡΠ°Π·Π³Π»Π΅ΠΆΠ΄Π° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ΡΠΎ ΠΈ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΠ°Π½Π΅ΡΠΎ Π½Π° Π½ΠΎΠ²ΠΎΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠ°Π½ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ Π½Π° ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½ΠΈΡ ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½. ΠΡΠΎΠ΄ΡΠ»ΠΆΠ°Π²Π°ΡΠΎΡΠΎ ΠΈ ΠΈΠ½ΡΠ΅Π½Π·ΠΈΠ²Π½ΠΎ ΠΈΠ·ΡΡΠ°Π²Π°Π½Π΅ Π½Π° ΡΠΎΠ»ΡΡΠ° Π½Π° ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈΡΠ΅ Π² ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° ΠΎΡ ΠΏΡΠΎΡΠ΅ΡΠΈ Π½Π° Π΄ΠΈΡΠ΅ΡΠ΅Π½ΡΠΈΠ°ΡΠΈΡ, ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ ΠΈ ΡΠ΅Π³ΡΠ»Π°ΡΠΈΡ Π½Π° ΠΊΠ»Π΅ΡΡΡΠ½ΠΈΡ ΡΠ°ΡΡΠ΅ΠΆ ΠΎΠ±ΡΡΠ»Π°Π²Ρ Π³ΠΎΠ»Π΅ΠΌΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» Π·Π° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π½Π° ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈ (Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½ΠΈ ΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½ΠΈ) ΠΏΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΠ΅ΡΠΎ Π½Π° ΡΠ΅Π΄ΠΈΡΠ° Π½Π°ΡΡΡΠ΅Π½ΠΈΡ, ΠΏΡΠΎΠΈΠ·ΡΠΈΡΠ°ΡΠΈ ΠΎΡ Π°Π½ΠΎΡΠΌΠ°Π»Π½ΠΎΡΠΎ ΠΊΠ»Π΅ΡΡΡΠ½ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅. ΠΠ°ΡΠΎ Ρ ΠΎΡΠΎΠ±Π΅Π½ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΡΠ΅ ΡΠ°Π·Π³Π»Π΅ΠΆΠ΄Π° Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡΠ° Π·Π° ΡΠΏΠΎΡΡΠ΅Π±Π°ΡΠ° ΠΈΠΌ Π² ΡΠ΅ΡΠ°ΠΏΠΈΡΡΠ° Π½Π° Π½Π΅ΠΎΠΏΠ»Π°ΡΡΠΈΡΠ½ΠΈ ΠΏΡΠΎΡΠ΅ΡΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°.
ΠΠ΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ΡΡ ΡΠ΅ ΠΎΡΠ½Π°ΡΡ ΠΊΡΠΌ ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΈΡΠ΅ ΠΎΡ ΡΡΠ΅ΡΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΠ΅ ΠΈ Π½Π°ΠΌΠΈΡΠ° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² ΡΠ΅ΡΠ°ΠΏΠΈΡΡΠ° Π½Π° Π’-ΠΊΠ»Π΅ΡΡΡΠ΅Π½ ΠΊΠΎΠΆΠ΅Π½ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌ. ΠΡΠ²Π΅Π½ ΡΡΠ²ΡΡΠ΄Π΅Π½ΠΎΡΠΎ ΡΠΈ ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΡΠ° ΡΠ΅Π΄ΠΈΡΠ° ΡΠ° Π΄Π°Π½Π½ΠΈΡΠ΅ Π·Π° Π΅ΡΠ΅ΠΊΡΠΈ ΠΏΡΠΈ Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ ΠΈ Π°Π²ΡΠΎΠΈΠΌΡΠ½Π½ΠΈ ΠΏΡΠΎΡΠ΅ΡΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°.
ΠΠ° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ Π΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ΅Π½Π° ΡΡΠΈΠ΅ΡΠ°ΠΏΠ½Π° ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½Π° ΡΡ
Π΅ΠΌΠ°, Π²ΠΊΠ»ΡΡΠ²Π°ΡΠ° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° Ρ
ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄ ΠΈ ΠΏΠΎΡΠ»Π΅Π΄Π²Π°ΡΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Ρ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»Π½ΠΈ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π΄ΠΎ ΡΠΎΡΠΌΠΈΡΠ°Π½Π΅ Π½Π° ΡΠ΅Π»Π΅Π²ΠΈΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈ. Π₯ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄-Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ²ΠΈΡΠ΅ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΏΡΠΈΠ²Π»ΠΈΡΠ°Ρ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ΡΠΎ ΠΏΡΠ΅Π· ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡΠ΅ Π½ΡΠΊΠΎΠ»ΠΊΠΎ Π΄Π΅ΡΠ΅ΡΠΈΠ»Π΅ΡΠΈΡ ΠΏΠΎΡΠ°Π΄ΠΈ ΡΠ°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·Π½ΠΈΡΠ΅ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ Π΅ΡΠ΅ΠΊΡΠΈ, ΠΊΠΎΠΈΡΠΎ ΠΏΡΠΈΡΠ΅ΠΆΠ°Π²Π°Ρ. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ Π΅, ΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈΡΠ΅ ΠΈ ΡΠ΅Ρ
Π½ΠΈΡΠ΅ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΠΏΡΠΎΡΠ²ΡΠ²Π°Ρ ΡΠΈΡΠΎΠΊ ΡΠΏΠ΅ΠΊΡΡΡ ΠΎΡ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈ Π΅ΡΠ΅ΠΊΡΠΈ ΠΊΠ°ΡΠΎ Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ΅Π½, ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΡΠ·ΠΏΠ°Π»ΠΈΡΠ΅Π»Π΅Π½, Π°Π½Π°Π»Π³Π΅ΡΠΈΡΠ΅Π½, Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½Π΅Π½, Π°Π½ΡΠΈΡ
Π΅Π»ΠΌΠΈΠ½ΡΠ΅Π½, ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ±Π΅ΡΠΊΡΠ»ΠΎΠ·Π΅Π½ ΠΈ Ρ.Π½. Π Π°Π·Π²ΠΈΡΠΈΠ΅ΡΠΎ Π½Π° Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ²ΠΈΡ ΠΊΠ»Π°Ρ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π±Π΅Π»Π΅ΠΆΠΈ Π·Π½Π°ΡΠΈΡΠ΅Π»Π΅Π½ ΠΏΡΠΎΠ³ΡΠ΅Ρ ΠΈ ΡΠ΅ ΡΠ°Π·ΠΊΡΠΈΠ²Π°Ρ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²ΠΎ Π½ΠΎΠ²ΠΈ Π°ΡΠΏΠ΅ΠΊΡΠΈ Π½Π° ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅.
ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ Ρ
ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄-Ρ
ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΈ ΡΠ° ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΠ°Π½ΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΠΎ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»Π½ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΈ Π²ΠΊΠ»ΡΡΠΈΡΠ΅Π»Π½ΠΎ ΠΏΡΠΈΠ»Π°Π³Π°Π½Π΅ Π½Π° ΠΈΠ½ΡΡΠ°ΡΠ΅ΡΠ²Π΅Π½Π° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΡ, 1Π-Π―ΠΠ -ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΡ ΠΈ ΠΌΠ°ΡΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡ. Π£ΡΠΏΠ΅ΡΠ½ΠΎ Π΅ ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ ΠΈ Π²Π°Π»ΠΈΠ΄ΠΈΡΠ°Π½ HPLC ΠΌΠ΅ΡΠΎΠ΄ Π·Π° ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ½Π΅ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ ΠΈ Π½Π΅Π³ΠΎΠ²ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΡΠ°ΠΌΠΎΡΡΠΎΡΡΠ΅Π»Π½ΠΎ ΠΈ Π² ΡΠΌΠ΅ΡΠΈ.
ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π° Π΅ ΠΎΡΠ΅Π½ΠΊΠ° Π½Π° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» Π½Π° Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½ΠΎΠ²ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΡΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° β ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ Π·Π° Π΅Π»Π΅ΠΊΡΡΠΎΠ½Π΅Π½ ΠΏΡΠ΅Π½ΠΎΡ β ABTS-ΡΠ΅ΡΡ, ΠΏΡΠ΅Π½ΠΎΡ Π½Π° Π²ΠΎΠ΄ΠΎΡΠΎΠ΄Π΅Π½ Π°ΡΠΎΠΌ-DPPH-ΡΠ΅ΡΡ, ΠΊΠ°ΠΊΡΠΎ ΠΈ ΠΏΠΎ Π΅Π»Π΅ΠΊΡΡΠΎΡ
ΠΈΠΌΠΈΡΠ΅Π½ ΠΏΡΡ.
Π‘ ΠΏΠΎΠΌΠΎΡΡΠ° Π½Π° ΡΠ΅ΠΎΡΠ΅ΡΠΈΡΠ½ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΈ ΡΡΠΏΠ΅ΡΠ½ΠΎ ΡΠ° ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠ°Π½ΠΈ Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈΡΠ΅ Π·Π° ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠ½ΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠ°Π½Π΅ Π½Π° Π±Π΅ΠΊΡΠ°ΡΠΎΡΠ΅Π½, ΠΎΡΠ΅Π½Π΅Π½ΠΈ ΡΠ° Π½Π΅Π³ΠΎΠ²ΠΈΡΠ΅ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈ ΠΈ Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΈ. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠ°Π½ΠΈ ΠΈ ΠΎΠ±ΠΎΠ±ΡΠ΅Π½ΠΈ ΡΠ° ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΈΡΠ΅, ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΊΠΎΠΈΡΠΎ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈΡΠ΅ Π½Π° Π½ΠΎΠ²ΠΎΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡΠ΅ ΡΡΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΌΠΎΠ³Π°Ρ Π΄Π° ΠΏΠΎΡΠ΅Π½ΡΠΈΠΈΡΠ°Ρ ΡΠ΅ΡΠ½ΠΎΠ΄ΡΠΎΠ±Π½ΠΎ ΡΠ²ΡΠ΅ΠΆΠ΄Π°Π½Π΅, ΡΡΠ΅Π· ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΈ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π½Π° Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Ρ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΈΡΠ΅ ΠΌΠ°ΠΊΡΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΠΈ (ΠΠΠ ΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΈ) Π² ΡΠ΅ΡΠ½ΠΈΡ Π΄ΡΠΎΠ±. Π‘ΡΡΠΎ ΡΠ°ΠΊΠ° Π΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° ΠΈ Π²ΡΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡΠ° Π·Π° ΠΏΠΎΠ»ΡΡΠ°Π²Π°Π½Π΅ Π½Π° Π΄Π΅ΡΠΌΠ°Π»Π½ΠΈ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΈ
QSAR modeling for prediction of binding to DNA or proteins of dermal metabolites of newly synthesized hydrazones
IntroductionOver the last decade, there has been a significant increase in the scientific knowledge about cancer, which has accordingly led to the development and increase of interest in new medicines and therapeutic approaches with potential applications in oncology. Activity research and the identification of potential therapeutic and toxic effects of bexarotene-like structures underpin the development of new approaches to the treatment of a number of untreated diseases.This requires a further and in-depth study of the potential of newly synthesized compounds to produce active metabolites.AimIn view of the potential for dermal administration of bexarotene, the potential for toxic metabolism in the skin needs to be investigated.Materials and MethodsFor the purpose the OECD (Q) SAR Application Toolbox was used. It is a software application for evaluating the properties of chemicals based on their molecular structure.ResultsThe application of the model for predicting metabolic changes makes it possible to assess the risk based on the chemical structure of the compounds.ConclusionThe skin metabolic prediction of new hydrazones of third-generation retinoid bexarotene indicates that not one of them predicts binding to DNA or proteins