{"title":"Phase behavior and biological activity of lyotropic liquid crystal systems doped with 1,2,3-triazole derivative","authors":"Natalia Selivanova , Marina Shulaeva , Alexandra Voloshina , Vyacheslav Semenov","doi":"10.1016/j.molliq.2024.126352","DOIUrl":null,"url":null,"abstract":"<div><div>Heterocyclic compounds are important for the synthesis of pharmaceuticals, especially substituted triazoles, which have high biological activity. The development of approaches to the creation of delivery systems for bioactive heterocyclic compounds is of particular importance for improving the biopharmaceutical aspects of therapy. In this work, we report synthesis and characterization of a new 1,2,3-triazole: ethyl 2-((1-decyl-1H-1,2,3-triazol-4-yl)methyl)-3-oxobutanoate (TR). The efficient incorporation into lyotropic mesophases as a drug delivery platform demonstrated. Polarized optical microscopy studies confirmed formation of a lyotropic mesophase in the binary P123/TR system as well as in tertiary systems with added water, ethanol, and DMSO. This allows to dope 5 % of triazole into lyomesophases. IR and UV spectroscopy studies detected intermolecular interactions occurring in the P123/TR system. Release of TR from binary and tertiary lyomesophases was studied. Impacts of composition and temperature on the release time were analyzed. Evaluation of cytotoxicity to M-Hela and HuTu-80 cancer lines and Chang Liver living cells revealed antitumor properties of the studied substituted 1,2,3-triazole. The lowest IC<sub>50</sub> of TR is 57 μg·mL<sup>−1</sup> toward HuTu-80. This is at the level of the reference drug Fluconazol. For the P123/DMSO/TR LLC system in concentration range of 31.3–124 µg·ml<sup>−1</sup>, the viability percentage of liver cells is comparable to those of cancer cells. These results demonstrate the potential opportunity for application LLC P123/DMSO used as a TR delivery for and enhance its antitumor effect.</div></div>","PeriodicalId":371,"journal":{"name":"Journal of Molecular Liquids","volume":"415 ","pages":"Article 126352"},"PeriodicalIF":5.3000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Liquids","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167732224024115","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Heterocyclic compounds are important for the synthesis of pharmaceuticals, especially substituted triazoles, which have high biological activity. The development of approaches to the creation of delivery systems for bioactive heterocyclic compounds is of particular importance for improving the biopharmaceutical aspects of therapy. In this work, we report synthesis and characterization of a new 1,2,3-triazole: ethyl 2-((1-decyl-1H-1,2,3-triazol-4-yl)methyl)-3-oxobutanoate (TR). The efficient incorporation into lyotropic mesophases as a drug delivery platform demonstrated. Polarized optical microscopy studies confirmed formation of a lyotropic mesophase in the binary P123/TR system as well as in tertiary systems with added water, ethanol, and DMSO. This allows to dope 5 % of triazole into lyomesophases. IR and UV spectroscopy studies detected intermolecular interactions occurring in the P123/TR system. Release of TR from binary and tertiary lyomesophases was studied. Impacts of composition and temperature on the release time were analyzed. Evaluation of cytotoxicity to M-Hela and HuTu-80 cancer lines and Chang Liver living cells revealed antitumor properties of the studied substituted 1,2,3-triazole. The lowest IC50 of TR is 57 μg·mL−1 toward HuTu-80. This is at the level of the reference drug Fluconazol. For the P123/DMSO/TR LLC system in concentration range of 31.3–124 µg·ml−1, the viability percentage of liver cells is comparable to those of cancer cells. These results demonstrate the potential opportunity for application LLC P123/DMSO used as a TR delivery for and enhance its antitumor effect.
期刊介绍:
The journal includes papers in the following areas:
– Simple organic liquids and mixtures
– Ionic liquids
– Surfactant solutions (including micelles and vesicles) and liquid interfaces
– Colloidal solutions and nanoparticles
– Thermotropic and lyotropic liquid crystals
– Ferrofluids
– Water, aqueous solutions and other hydrogen-bonded liquids
– Lubricants, polymer solutions and melts
– Molten metals and salts
– Phase transitions and critical phenomena in liquids and confined fluids
– Self assembly in complex liquids.– Biomolecules in solution
The emphasis is on the molecular (or microscopic) understanding of particular liquids or liquid systems, especially concerning structure, dynamics and intermolecular forces. The experimental techniques used may include:
– Conventional spectroscopy (mid-IR and far-IR, Raman, NMR, etc.)
– Non-linear optics and time resolved spectroscopy (psec, fsec, asec, ISRS, etc.)
– Light scattering (Rayleigh, Brillouin, PCS, etc.)
– Dielectric relaxation
– X-ray and neutron scattering and diffraction.
Experimental studies, computer simulations (MD or MC) and analytical theory will be considered for publication; papers just reporting experimental results that do not contribute to the understanding of the fundamentals of molecular and ionic liquids will not be accepted. Only papers of a non-routine nature and advancing the field will be considered for publication.