Potential Antileukemic and Immunosuppressive Drugs. II. Further Studies with Benzo-2,1,3-oxadiazoles (Benzofurazans) and Their N-Oxides (Benzofuroxans)
“…Benzofuroxans can be used as in vitro inhibitors of RNA synthesis in sheep lymphocytes, being potent antileukemic and immunosuppressive drugs. [472][473][474] Derivatives of benzofuroxan, such as furazanobenzofuroxan, furoxanobenzofuroxan, and furoxanobenzothiadiazole, have been found to be potent in vivo and in vitro vasodilators. [475][476][477]…”
Section: Applicationsmentioning
confidence: 99%
“…There have been several comprehensive reviews regarding their chemistry. − Furoxans have been shown to exert a variety of NO-related bioactivities, including cytotoxicity, mutagenicity, immunosuppression, central muscle relaxant properties, anticonvulsive effects, monoamino oxidase inhibition, and direct vasodilator and blood pressure lowering activities. Benzofuroxans can be used as in vitro inhibitors of RNA synthesis in sheep lymphocytes, being potent antileukemic and immunosuppressive drugs. − Derivatives of benzofuroxan, such as furazanobenzofuroxan, furoxanobenzofuroxan, and furoxanobenzothiadiazole, have been found to be potent in vivo and in vitro vasodilators. − 20 …”
“…Benzofuroxans can be used as in vitro inhibitors of RNA synthesis in sheep lymphocytes, being potent antileukemic and immunosuppressive drugs. [472][473][474] Derivatives of benzofuroxan, such as furazanobenzofuroxan, furoxanobenzofuroxan, and furoxanobenzothiadiazole, have been found to be potent in vivo and in vitro vasodilators. [475][476][477]…”
Section: Applicationsmentioning
confidence: 99%
“…There have been several comprehensive reviews regarding their chemistry. − Furoxans have been shown to exert a variety of NO-related bioactivities, including cytotoxicity, mutagenicity, immunosuppression, central muscle relaxant properties, anticonvulsive effects, monoamino oxidase inhibition, and direct vasodilator and blood pressure lowering activities. Benzofuroxans can be used as in vitro inhibitors of RNA synthesis in sheep lymphocytes, being potent antileukemic and immunosuppressive drugs. − Derivatives of benzofuroxan, such as furazanobenzofuroxan, furoxanobenzofuroxan, and furoxanobenzothiadiazole, have been found to be potent in vivo and in vitro vasodilators. − 20 …”
“…In contrast to BFZs that react with specific functional groups, exposure to broadly reactive BFZs often prompts toxicity, as evidenced by the interruption of DNA, RNA, and peptide syntheses in cultured tumor cells. The toxicities of broadly reactive BFZs are thought to correlate with the characteristics of electron withdrawing groups (Ghosh et al 1972, 1981; Ghosh and Whitehouse 1968, 1969; Whitehouse and Ghosh 1968). …”
Here, we report on 7-nitro-4-(phenylthio) benzofurazan (NBF-SPh), the most potent derivative among a set of patented anticancer 7-nitrobenzofurazans (NBFs), which have been suggested to function by perturbing protein–protein interactions. We demonstrate that NBF-SPh participates in toxic redox-cycling, rapidly generating reactive oxygen species (ROS) in the presence of molecular oxygen, and this is the first report to detail ROS production for any of the anticancer NBFs. Oxygraph studies showed that NBF-SPh consumes molecular oxygen at a substantial rate, rivaling even plumbagin, menadione, and juglone. Biochemical and enzymatic assays identified superoxide and hydrogen peroxide as products of its redox-cycling activity, and the rapid rate of ROS production appears to be sufficient to account for some of the toxicity of NBF-SPh (LC50 = 12.1 µM), possibly explaining why tumor cells exhibit a sharp threshold for tolerating the compound. In cell cultures, lipid peroxidation was enhanced after treatment with NBF-SPh, as measured by 2-thiobarbituric acid-reactive substances, indicating a significant accumulation of ROS. Thioglycerol rescued cell death and increased survival by 15-fold to 20-fold, but pyruvate and uric acid were ineffective protectants. We also observed that the redox-cycling activity of NBF-SPh became exhausted after an average of approximately 19 cycles per NBF-SPh molecule. Electrochemical and computational analyses suggest that partial reduction of NBF-SPh enhances electrophilicity, which appears to encourage scavenging activity and contribute to electrophilic toxicity.
“…The crude material should be recrystallized in an excess of refluxing benzene. A BTFhenzene complex formed can be decomposed to obtain high-purity BTF by heating in vacuum above 80 "C. Liao Zhiyuan and Chen Boren (36) reported that the hydrogen-free compound 6,6-dinitro-tetrafuroxano- The molecular structure of 5-methylamino-4-nitrofuroxano[4,3-h]benzofuroxan was determined by X-ray diffraction. It is the first example of benzofuroxans that exocyclic oxygen atoms of two furoxano groups on the same molecule are neighbouring each other.…”
This paper reviews on benzofuroxan system compounds about structure, preparation and development. The replacement of nitro groups by furoxano groups on aromatic ring can increase density, detonation velocity and energy of explosives, so benzofuroxan system compounds and some energetic materials have aroused much attention.
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