RESUMO
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-butylthiacalix[4]arene 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 thiacalix[4]arene 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.
Assuntos
Antibacterianos/síntese química , Calixarenos/síntese química , Compostos de Amônio Quaternário/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Compostos de Benzalcônio/farmacologia , Calixarenos/farmacologia , Clorexidina/farmacologia , Desenho de Fármacos , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A novel organic compound 9-(2,4-dinitrophenyloxy)-3,3,8-trimethyl-1,5-dihydro-[1,3]dioxepino[5,6-c]pyridine (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 UVVis spectrum. The second harmonic generation (SHG) test has shown that DNPAP possesses 6.4-times higher NLO efficiency compared to KDP.