Synthesis and biological evaluation of 2,4-diaminopteridine derivatives as nitric oxide synthase inhibitor

Ma, Fei; Lü, Gang; Zhou, Wei; Wang, Qiu Juan; Zhang, Yi Hua; Yao, Qi

doi:10.1016/j.cclet.2008.12.012

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…Regarding iNOS, several 2,4‐aminopteridines have also been shown to inhibit this isoform, even with better results than MTX . Compounds 70a (2‐amino‐4‐((4‐ethoxylcarbonylphenyl)amino)‐6‐phenylpteridine) and 70b (2‐amino‐4‐isopropylamine‐6‐(4‐methoxyphenyl)‐pteridine) were further analyzed in induced septic shock and immunological liver injury in rats.…”

Section: Other Activitiesmentioning

confidence: 99%

Therapeutic potential of pteridine derivatives: A comprehensive review

Carmona‐Martínez

Ruiz–Alcaraz

Vera

et al. 2018

Medicinal Research Reviews

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Pteridines are aromatic compounds formed by fused pyrazine and pyrimidine rings. Many living organisms synthesize pteridines, where they act as pigments, enzymatic cofactors, or immune system activation molecules. This variety of biological functions has motivated the synthesis of a huge number of pteridine derivatives with the aim of studying their therapeutic potential. This review gathers the state‐of‐the‐art of pteridine derivatives, describing their biological activities and molecular targets. The antitumor activity of pteridine‐based compounds is one of the most studied and advanced therapeutic potentials, for which several molecular targets have been identified. Nevertheless, pteridines are also considered as very promising therapeutics for the treatment of chronic inflammation‐related diseases. On the other hand, many pteridine derivatives have been tested for antimicrobial activities but, although some of them resulted to be active in preliminary assays, a deeper research is needed in this area. Moreover, pteridines may be of use in the treatment of many other diseases, such as diabetes, osteoporosis, ischemia, or neurodegeneration, among others. Thus, the diversity of the biological activities shown by these compounds highlights the promising therapeutic use of pteridine derivatives. Indeed, methotrexate, pralatrexate, and triamterene are Food and Drug Administration approved pteridines, while many others are currently under study in clinical trials.

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Section: Other Activitiesmentioning

confidence: 99%

Therapeutic potential of pteridine derivatives: A comprehensive review

Carmona‐Martínez

Ruiz–Alcaraz

Vera

et al. 2018

Medicinal Research Reviews

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“…Current Issues in Pharmacy and Medical Sciences [7][8][9][10][11][12][13][14]. Moreover, the folates themselves, as noted above, are essential nutrients and are involved in various metabolic processes, including the formation of methionine, which in turn is used for the synthesis of S-adenosylmethionine, as a universal donor of the methyl group [6].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the toxicity and hepatoprotective properties of new s-substituted pteridins

Groma

Берест

Antypenko

et al. 2023

Current Issues in Pharmacy and Medical Sciences

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Liver damage is a common problem around the world, and pharmacocorrection of such disease is carried out by administration of various drugs. Natural and synthetic thio-containing compounds are important in this respect. Most of these, however, have side effects and do not always meet the criteria of evidence-based medicine. Therefore, the search for new drugs with hepatoprotective properties, characterized by high efficiency and low toxicity, is an urgent problem of current pharmacology and biochemistry. The purpose of this study was to assess the acute toxicity of new potentially bioactive S-substituted pteridinones, to select the least toxic substance, to improve the pharmaco-technological characteristics, and to study the hepatoprotective properties in an experimental model of tetrachloromethane hepatitis in rats. Herein, comparison of the hepatoprotective properties of compound 4.1 and the reference drug "Thiotriazoline" is based on biochemical studies. The research results showed that sub-stance 4.1 had a positive effect on biochemical processes by increasing the compensatory mechanisms of antioxidant systems, while reducing the infiltrative, destructive and inflamma-tory process in the liver, evoking decreases in the cytolytic process, restoring the structure of the components of the membrane of hepatocytes, stabilizing and enhancing the functional activity of the liver, restoring the liver’s protein-synthesizing function and increasing the abil-ity to restore metabolic disorders in the liver. As a result of the biochemical study of the hepa-toprotective effect of compound 4.1, it was found that the studied substance is a non-toxic compound with antioxidant properties.

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“…2-Amino-4-piperazin-1-yl-6-(3,4-dimethoxyphenyl)-pteridines have been shown to possess immunosuppressive and anti-inflammatory properties [ 13 ], and analogues of the potent phosphodiesterase-4 inhibitor 7-benzylamino-6-chloro-2-piperazin-1-yl-4-pyrrolidin-1-ylpteridine which inhibits growth in tumor cell lines required a 2-piperazin-1-yl substituent for optimal potency [ 14 ]. Some 2-amino-4-( N,N -diarylmethyl)-6-arylpteridines inhibit neuronal nitric oxide synthase [ 15 ] and some 2,4-diamino-4,6-diarylpteridines inhibit inducible or inflammatory nitric oxide synthase [ 16 ]. Several 2,4-diamino-6-arylaminomethylpteridines are potent inhibitors of parasitic pteridine reductases, and have promising antiparasitic potential [ 17 , 18 ].…”

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confidence: 99%

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

et al. 2015

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BackgroundReactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.ResultsA novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).ConclusionThe 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.

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Synthesis and biological evaluation of 2,4-diaminopteridine derivatives as nitric oxide synthase inhibitor

Cited by 4 publications

References 6 publications

Therapeutic potential of pteridine derivatives: A comprehensive review

Therapeutic potential of pteridine derivatives: A comprehensive review

Evaluation of the toxicity and hepatoprotective properties of new s-substituted pteridins

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

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