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•New antibacterial and bactericidal agents based on thiacalixarene are created.•Thiacalix4arene derivatives in 1,3-alternate conformation are the most effective.•The compounds are ...less toxic than chlorhexidine, miramistin and benzalkonium chloride.•The different type of interaction of the compounds with DPPC lipid membranes is shown.
The search for new antibacterial and antiseptic drugs is an urgent problem due to the resistance of microorganisms to existing drugs. In this work, for the first time, the design of antibacterial and bactericidal agents based on quaternary ammonium compounds on thiacalixarene macrocyclic platform was proposed and implemented. A series of tetrasubstituted quaternary ammonium salts with different nature and length of the substituent (-N+(CH3)2R, R = CH2Ph, CnH2n+1, n = 1, 4, 8, 10) based on p-tert-butylthiacalix4arene in cone and 1,3-alternate conformations was obtained with excellent yields. The obtained compounds have a high antibacterial effect against Gram-positive (S. aureus, S. epidermidis, B. subtilis) bacteria comparable with commercial antiseptics chlorhexidine, miramistin and benzalkonium chloride. It was found that quaternary ammonium derivatives of thiacalix4arene in 1,3-alternate conformation more effectively inhibit the growth of the tested bacterial strains in comparison with compounds in cone conformation. Cytotoxicity studies on human skin fibroblast (HSF) cells demonstrated that all compounds were less toxic compared to reference drugs. The different type of interaction of the studied compounds with model DPPC lipid membranes explains different antibacterial activity and cytotoxicity of compounds. The compounds in cone conformation are adsorbed on the DPPC vesicles membrane surface, while the incorporation of lipophilic alkyl fragments of macrocycles in 1,3-alternate conformation into the membrane leads to “clumping” of DPPC vesicles. It was shown the saving of antibacterial activity of thiacalixarene derivatives in 1,3-alternate conformation on Gram-positive clinical strains. The obtained results allow viewing the described thiacalixarene based quaternary ammonium compounds as promising molecules in the development of the new antibacterial agents.
A library of 31 mono- and bis-quaternary ammonium compounds based on 3-hydroxypyridine was synthesized. Primary screening of their antibacterial activity
in vitro
in six archival strains of bacteria ...revealed four highly active lead compounds surpassing commercial antiseptics benzalkonium chloride, miramistin, and chlorhexidine in their activity. Further in-depth study of the antibacterial activity of the lead compounds
in vitro
in 16 clinical bacterial strains and the study of their toxicity
in vitro
and
in vivo
showed that 2,6-bis(N,N-dimethyl-N-dodecylammoniomethyl)-3-methoxypyridine dichloride was the most active and least toxic and manifested a higher activity in comparison with benzalkonium chloride, miramistin, and chlorhexidine in clinical isolate of both gram-positive and gram-negative bacteria, as well as a moderate toxicity
in vivo
(LD
50
= 82 6 mg kg
−1
, mice, oral administration). The quaternary ammonium compounds based on 3-hydroxypyridine are of undoubted interest for the further development of antibacterial drugs.
A new method for the synthesis of 6-hydroxypyridoxine and its seven-membered acetals has been developed. The synthesized compounds have high antioxidant activity, which is not inferior to the ...reference drugs, i.e., ascorbic acid and trolox. The seven-membered ketal of 6-hydroxypyridoxine effectively penetrates the cytoplasmic membrane of cells.
Chemistry of pyridoxine in drug design Shtyrlin, Y. G.; Petukhov, A. S.; Strelnik, A. D. ...
Russian chemical bulletin,
05/2019, Letnik:
68, Številka:
5
Journal Article
Recenzirano
Pyridoxine and its derivatives, pyridoxamine and pyridoxal, are the three main forms of vitamin B
6
, which play exceptionally important biological roles in living organisms. The active endogenous ...metabolites of these molecules, pyridoxal phosphate and pyridoxamine phosphate, are the most important coenzymes involved in a wide range of biochemical reactions necessary for cell activity, due to which pyridoxine and its derivatives are regarded as biologically privileged molecules. Taking into account also the wide possibilities for chemical modification of the pyridoxine structure, it is only natural for medicinal chemists to explore them in the design of novel drugs. This review summarizes the data on the main pharmacologically significant pyridoxine derivatives (including pyridoxamine and pyridoxal derivatives) reported in modern scientifi c and patent sources. Methods for their synthesis, key pharmacological properties, and medicinal chemistry concepts underlying the design of the developing physiologically active compounds are presented. The promising directions for future development of chemistry of physiologically active pyridoxine derivatives are also discussed.
•A novel organic nonlinear optical material DNPAP has been synthesized.•It has good physicochemical properties suitable for second harmonic generation.•The SHG efficiency of DNPAP is found to be 6.4 ...times better than that of KDP.
A novel organic compound 9-(2,4-dinitrophenyloxy)-3,3,8-trimethyl-1,5-dihydro-1,3dioxepino5,6-cpyridine (DNPAP) has been synthesized and a nonlinear optical (NLO) crystal has been grown by slow evaporation method. Compound was subjected to different characterization analyses in order to find out its suitability for optoelectronic applications. Single crystal and powder X-ray diffraction analyses show that DNPAP crystallizes in the orthorhombic space group Pca21. The range of optical absorption was ascertained by recording UV–Vis spectrum. The second harmonic generation (SHG) test has shown that DNPAP possesses 6.4-times higher NLO efficiency compared to KDP.
Pyridoxine derivatives, 3-hydroxy-2-methylpyridine-4- and -5-carbohydrazides, were synthesized according to optimized known procedures, and a method for the synthesis of ...5-(hydroxymethyl)-2,2,8-trimethyl-4
H
-1,3dioxino4,5-
c
pyridine-6-carbohydrazide was developed. The hydroxymethyl groups in positions 5 and 6 of 2,2,8-trimethyl-4
H
-1,3dioxino4,5-
c
pyridine showed different reactivities, and only the 6-hydroxymethyl group was selectively oxidized to aldehyde under mild conditions. The lactone ring in 5,6-dihydrofuro3,4-
b
pyridin-7(5
H
)-one was found to be stable to nucleophiles. The synthesized hydrazides showed no antimycobacterial activity.
Methods for the synthesis of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine were developed. Some of obtained compounds possess high antibacterial and antitumor activity
...in vitro
.
Using the methods of pH-metry and mathematical simulation, we studied the complex formation in the copper(II)–malonic (L)/adipic acid (L')–L-histidine (HisH) ternary systems in aqueous medium against ...1.0 M KNO
3
solution at 25.0°C. The stability constants of (1 : 1 : 1) heteroligand complexes were determined. Quantum chemical calculations of the structures of heteroligand complexes were performed. It was revealed that the Cu(His)(L)
+
and Cu(His)(L')
+
complexes exist predominantly in the
cis
-form.
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