69467-93-2Relevant academic research and scientific papers
Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability
Braga, Cláudia,Vaz, Ana R.,Oliveira, M. Concei??o,Matilde Marques,Moreira, Rui,Brites, Dora,Perry, Maria J.
, p. 16 - 25 (2019/04/04)
Herein we report novel hybrid compounds based on valproic acid and DNA-alkylating triazene moieties, 1, with therapeutic potential for glioblastoma multiforme chemotherapy. We identified hybrid compounds 1d and 1e to be remarkably more potent against glioma and more efficient in decreasing invasive cell properties than temozolomide and endowed with chemical and plasma stability. In contrast to temozolomide, which undergoes hydrolysis to release an alkylating metabolite, the valproate hybrids showed a low potential to alkylate DNA. Key physicochemical properties align for optimal CNS penetration, highlighting the potential of these effective triazene based-hybrids for enhanced anticancer chemotherapy.
The selective cytotoxicity of new triazene compounds to human melanoma cells
Sousa, Ana,Santos, Fábio,Gaspar, Maria Manuela,Calado, Susana,Pereira, Jo?o D.,Mendes, Eduarda,Francisco, Ana Paula,Perry, Maria Jesus
, p. 3900 - 3910 (2017/07/05)
Metastatic melanoma still remains one the most difficult cancers to overcome. The aim of our research was the design of anti-tumour triazene compounds 3 for application to a melanoma-specific therapy. The strategy exploits the unique enzyme pathway of melanin biosynthesis for conversion of non-toxic prodrugs into toxic drugs in the melanoma cell. The compounds 3 were designed by coupling two active moieties, the alkylating triazenes and different tyrosinase substrates. All compounds 3 revealed to be chemically stable in isotonic phosphate buffer (PBS) at physiologic pH (t??≥?48?h), and most of them showed to be slowly hydrolysed in human plasma (1.5?≤?t? (h)?≤?161). Compounds 3c–n revealed to be excellent tyrosinase substrates (0.74?≤?t? (min)?≤?6) with the best tyrosinase substrate 3l releasing MMT 45?s after tyrosinase activation. Structure-activity relationship studies allowed the identification of the better structural features for enzyme affinity. Furthermore, the derivatives 3l and 3m showed cell selectivity with significant cytotoxic effects (IC50 values of 46–65?μM) against melanoma cell lines with tyrosinase overexpression MNT-1 and B16F10.
Studies of the mode of action of antitumor triazenes and triazines. 6. 1-Aryl-3-(hydroxymethyl)-3-methyltriazenes: Synthesis, chemistry, and antitumor properties
Vaughan,Tang,Llanos,Horton,Simmonds,Hickman,Stevens
, p. 357 - 363 (2007/10/02)
1-Aryl-3-(hydroxymethyl)-3-alkyltriazenes [ArN=NN(CH3)CH2OH] have been synthesized by diazonium coupling to the carbinolamine (RNHCH2OH), generated in situ from the alkylamine and formaldehyde mixtures. The (hydroxymethyl)triazene structure has been confirmed by IR, NMR, and mass spectral analysis and also by the preparation of a crystalline benzoate derivative. The mass spectra of the (hydroxymethyl)triazenes suggest that they fragment by loss of formaldehyde to give the methyltriazene, which is also the product of hydrolysis in solution. The degradation of the (hydroxymethyl)triazenes in solution has been followed by UV spectroscopy and by HPLC analysis, and the half-lives were determined under a variety of conditions. The half-lives of the corresponding methyl- and (hydroxymethyl)triazenes are very similar. Both methyl- and (hydroxymethyl)triazenes decompose on silica plates during TLC analysis to give products consistent with known diazo-migration reactions. The (hydroxymethyl)triazenes have pronounced antitumor activity against the TLX5 tumor in vivo; in vivo-in vitro bioassay experiments suggest that the (hydroxymethyl)triazenes exert their in vivo antitumor activity via the degradation product, the alkyltriazene.
Triazenes: A Reinvestigation of the Coupling Reaction between Aryldiazonium Ions and Methylamine/Formaldehyde Mixtures
Cheng, Shee C.,Sousa Fernandes, M. Leonor de,Iley, Jim,Rosa, M. Eduarda N.
, p. 1101 - 1113 (2007/10/02)
Aryldiazonium fluoroborates react with methylamine/formaldehyde mixtures to give bismethylamines rather than 1-aryl-3-hydroxymethyl-3-methyltriazenes as previously reported.Aryldiazonium chlorides react with methylamin
N,N-Bis-(1-aryl-3-methyltriazen-3-ylmethyl)methylamines (1,9-Diaryl-3,5,7-trimethyl-1,2,3,5,7,8,9-hepta-azanona-1,8-dienes): Novel Coupling Products from the Reaction of Arenediazonium Ions with Methylamine and Formaldehyde
Lafrance, Ronald J.,Tang, York,Vaughan, Keith,Hooper Donald L.
, p. 721 - 722 (2007/10/02)
The reaction of arenediazonium ions with aqueous formaldehyde-methylamine solutions affords mixtures of the 3-hydroxymethyltriazenes, ArN=NN(Me)CH2OH, and the previously unreported bis(triazenylmethyl)methylamines, ArN=NN(Me)CH2N(Me)CH2N(Me)N=NAr.
