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Investigational New Drugs Aug 2020This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell...
This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Humans; Membrane Potential, Mitochondrial; Proto-Oncogene Proteins c-bcl-2; Triazines
PubMed: 31520321
DOI: 10.1007/s10637-019-00838-9 -
Molecules (Basel, Switzerland) Feb 2021Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two...
Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines-HCT116 and SW620. and which are the derivatives containing -hydroxyphenyl substituents exhibited the highest activity with IC against both cell lines in the range of 20-27 µM, which is comparable to the IC of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative . Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, "CaCit- NPs" were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of from the synthesised CaCit- NPs is pH-responsive, and could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.
Topics: Antineoplastic Agents; Biguanides; Calcium Citrate; Cell Line, Tumor; Drug Liberation; Humans; Nanoparticles; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; Triazines
PubMed: 33672071
DOI: 10.3390/molecules26041028 -
Molecules (Basel, Switzerland) Apr 2022A series of novel 1,4-dihydrobenzo[1,2,4][]triazines bearing an acetyl or ester moiety as a functional group at the C(3) atom of the 1,2,4-triazine ring were...
A series of novel 1,4-dihydrobenzo[1,2,4][]triazines bearing an acetyl or ester moiety as a functional group at the C(3) atom of the 1,2,4-triazine ring were synthesized. The synthetic protocol is based on an oxidative cyclization of functionally substituted amidrazones in the presence of DBU and Pd/C. It was found that the developed approach is suitable for the preparation of 1,4-dihydrobenzo[][1,2,4]triazines, but the corresponding Blatter radicals were isolated only in few cases. In addition, a previously unknown dihydrobenzo[][1,2,4]triazolo[3,4-][1,2,4]triazine tricyclic open-shell derivative was prepared. Studies of thermal behavior of the synthesized 1,4-dihydrobenzo[1,2,4][]triazines revealed their high thermal stability (up to 240-250 °C), which enables their application potential as components of functional organic materials.
Topics: Cyclization; Triazines
PubMed: 35458773
DOI: 10.3390/molecules27082575 -
Molecules (Basel, Switzerland) Jan 2021Conventional methods employed today for the synthesis of amides often lack of economic and environmental sustainability. Triazine-derived quaternary ammonium salts,...
Conventional methods employed today for the synthesis of amides often lack of economic and environmental sustainability. Triazine-derived quaternary ammonium salts, e.g., 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM(Cl)), emerged as promising dehydro-condensation agents for amide synthesis, although suffering of limited stability and high costs. In the present work, a simple protocol for the synthesis of amides mediated by 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and a -amine has been described and data are compared to DMTMM(Cl) and other CDMT-derived quaternary ammonium salts (DMT-Ams(X), X: Cl or ClO). Different -amines (Ams) were tested for the synthesis of various DMT-Ams(Cl), but only DMTMM(Cl) could be isolated and employed for dehydro-condensation reactions, while all CDMT/-amine systems tested were efficient as dehydro-condensation agents. Interestingly, in best reaction conditions, CDMT and 1,4-dimethylpiperazine gave -phenethyl benzamide in 93% yield in 15 min, with up to half the amount of -amine consumption. The efficiency of CDMT/-amine was further compared to more stable triazine quaternary ammonium salts having a perchlorate counter anion (DMT-Ams(ClO)). Overall CDMT/-amine systems appear to be a viable and more economical alternative to most dehydro-condensation agents employed today.
Topics: Amides; Amines; Benzamides; Carboxylic Acids; Chemistry Techniques, Synthetic; Perchlorates; Phenethylamines; Piperazines; Quaternary Ammonium Compounds; Solvents; Triazines
PubMed: 33401732
DOI: 10.3390/molecules26010191 -
International Journal of Nanomedicine 2022The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of...
BACKGROUND
The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.
METHODS
Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and HDCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy).
RESULTS
Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.
CONCLUSION
Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.
Topics: Carcinoma; Humans; Rose Bengal; Silanes; Triazines
PubMed: 35321027
DOI: 10.2147/IJN.S352349 -
International Journal of Molecular... Nov 2022Methods for the synthesis of two types of isomeric dispirocompounds based on imidazothiazolotriazine and pyrrolidineoxindole, differing in the structure of...
Methods for the synthesis of two types of isomeric dispirocompounds based on imidazothiazolotriazine and pyrrolidineoxindole, differing in the structure of imidazothiazolotriazine fragment, namely, linear dispiro[imidazo[4,5-]thiazolo[3,2-][1,2,4]triazine-6,3'-pyrrolidine- 4',3″-indolines] and angular dispiro[imidazo[4,5-]thiazolo[2,3-][1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] were proposed. The first method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from paraformaldehyde and N-alkylglycine derivatives to the corresponding oxindolylidene derivatives of imidazothiazolotriazine. The cycloaddition leads to a mixture of two diastereomers resulted from - and -approaches of azomethine ylide in approximately a 1:1 ratio, which were separated by column chromatography. Another method consists in rearrangement of linear dispiro[imidazo[4,5-]thiazolo[3,2-][1,2,4]triazine-6,3'-pyrrolidine-4',3″-indolines] into hitherto unavailable angular dispiro[imidazo[4,5-]thiazolo[2,3-]-[1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] upon treatment with KOH. It was found that the -diastereomer of linear type underwent rearrangement into the isomeric angular -diastereomer, while the rearrangement of the linear -diastereomer gave the angular -diastereomer.
Topics: Spiro Compounds; Thiosemicarbazones; Pyrrolidines; Triazines
PubMed: 36430300
DOI: 10.3390/ijms232213820 -
Toxicology in Vitro : An International... Mar 2021Here we demonstrate an animal-free skin permeation analytical approach suitable for testing pharmaceuticals, cosmetics, occupational skin hazards and skin allergens. The...
Here we demonstrate an animal-free skin permeation analytical approach suitable for testing pharmaceuticals, cosmetics, occupational skin hazards and skin allergens. The method aims to replace or significantly reduce existing in-vivo models and improve on already established in-vitro models. This by offering a more sensitive and flexible analytical approach that can replace and/or complement existing methods in the OECD guidelines for skin adsorption (no 427 and no 428) and measure multiple compounds simultaneously in the skin while being able to also trace endogenous effects in cells. We demonstrate this here by studying how active ingredients in sunscreen permeate through left-over human skin, from routine surgery, in a in a Franz-cell permeation model. Two common sunscreens were therefore applied to the human skin and Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to trace the molecules through the skin. We show that that ToF-SIMS imaging can be applied in visualizing the distribution of Avobenzone, Bemotrizinol, Biscotrizole and Ethyl hexyl triazine at subcellular resolution in the skin. The UV-blockers could be visualized at the same time in one single experiment without any probes or antibodies used. The UV-blockers mostly remained in the stratum corneum. However, in certain features of the skin, such as sebaceous glands, the penetration of the UV-blockers was more prominent, and the compounds reached deeper into the epidermis.
Topics: Animal Testing Alternatives; Humans; In Vitro Techniques; Phenols; Propiophenones; Skin; Skin Absorption; Spectrometry, Mass, Secondary Ion; Sunscreening Agents; Triazines
PubMed: 33276055
DOI: 10.1016/j.tiv.2020.105062 -
Molecules (Basel, Switzerland) Jun 2022In this paper, we present for the first time the evaluation of cytotoxicity and genotoxicity of de novo synthesized pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine...
In this paper, we present for the first time the evaluation of cytotoxicity and genotoxicity of de novo synthesized pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine sulfonamides , , and in human tumor cell lines: HeLa, HCT 116, PC-3, and BxPC-3. Cytotoxic and genotoxic properties of the tested compounds were estimated using the MTT assay, comet assay (alkaline and neutral version), and γ-H2AX immuno-staining. Examined sulfonamides exhibited strong anticancer properties towards tested cells in a very low concentration range (IC = 0.17-1.15 μM) after 72 h exposure time. The results of the alkaline and neutral version of the comet assay following 24 h incubation of the cells with tested compounds demonstrated the capability of heterocycles to induce significant DNA damage in exposed cells. HCT 116 cells were the most sensitive to the genotoxic activity of novel tricyclic pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine sulfonamides in the neutral version of the comet assay. Immunocytochemical detection of γ-H2AX showed an increase in DNA DSBs level in the HCT 116 cell line, after 24 h incubation with all tested compounds, confirming the results obtained in the neutral comet assay. Among all investigated compounds, showed the strongest cytotoxic and genotoxic activity toward all tested cell types. In conclusion, our results suggest that , , and exhibit high cytotoxic and genotoxic potential in vitro, especially towards the colorectal cancer cell line HCT 116. However, further investigations and analyses are required for their future implementation in the field of medicine.
Topics: Antineoplastic Agents; Cell Line, Tumor; Comet Assay; DNA Damage; Humans; Sulfanilamide; Sulfonamides; Triazines
PubMed: 35744887
DOI: 10.3390/molecules27123761 -
Journal of the American Chemical Society Dec 2019Despite their major biological and pharmacological significance, the structural and functional study of membrane proteins remains a significant challenge. A main issue...
Despite their major biological and pharmacological significance, the structural and functional study of membrane proteins remains a significant challenge. A main issue is the isolation of these proteins in a stable and functional state from native lipid membranes. Detergents are amphiphilic compounds widely used to extract membrane proteins from the native membranes and maintain them in a stable form during downstream analysis. However, due to limitations of conventional detergents, it is essential to develop novel amphiphiles with optimal properties for protein stability in order to advance membrane protein research. Here we designed and synthesized 1,3,5-triazine-cored dimaltoside amphiphiles derived from cyanuric chloride. By introducing variations in the alkyl chain linkage (ether/thioether) and an amine-functionalized diol linker (serinol/diethanolamine), we prepared two sets of 1,3,5-triazine-based detergents. When tested with several model membrane proteins, these agents showed remarkable efficacy in stabilizing three transporters and two G protein-coupled receptors. Detergent behavior substantially varied depending on the detergent structural variation, allowing us to explore detergent structure-property-efficacy relationships. The 1,3,5-triazine-based detergents introduced here have significant potential for membrane protein study as a consequence of their structural diversity and universal stabilization efficacy for several membrane proteins.
Topics: Alkylation; Detergents; Hydrophobic and Hydrophilic Interactions; Maltose; Membrane Proteins; Protein Stability; Triazines
PubMed: 31809039
DOI: 10.1021/jacs.9b07883 -
Molecules (Basel, Switzerland) Jan 20197-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this...
7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position. This electron N-lone pair activation overrides the activation/deactivation effects of some other substituents. The reaction time was significantly reduced with the use of microwave irradiation at 120 °C and 7 bar. The cytotoxicity and cyclic voltammetry measurements for 8-fluoro-1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one () are presented and compared with its synthetic precursor, 1,3-diphenylbenzo[][1,2,4]triazin-7(1)-one ().
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Diazonium Compounds; Halogenation; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Structure; Structure-Activity Relationship; Triazines
PubMed: 30646524
DOI: 10.3390/molecules24020282