Benzofurazans and benzofuroxans: Biochemical and pharmacological properties

Ghosh, Peter; Ternai, B.; Whitehouse, M. W.

doi:10.1002/med.2610010203

Cited by 74 publications

(22 citation statements)

References 97 publications

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“…The electrophilic character of nitro-2,1,3-benzoxadiazoles derivatives is particularly remarkable in the case of halo-nitrobenzofurazans that easily undergo to nucleophilic aromatic substitutions reactions (SN Ar ) leading to several analytical and biochemical applications [9][10][11][12][13][14]. In particular, due to the facility of its reaction with amino and thiol derivatives, the 4-chloro-7-nitrobenzofurazan was largely used in protein labeling reagent and for structure determination of enzymes [9,10,[12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Molecular structure, vibrational, UV and NBO analysis of 4-chloro-7-nitrobenzofurazan by DFT calculations

Kurt

Babu

Sundaraganesan

et al. 2011

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

131

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Section: Introductionmentioning

confidence: 99%

Molecular structure, vibrational, UV and NBO analysis of 4-chloro-7-nitrobenzofurazan by DFT calculations

Kurt

Babu

Sundaraganesan

et al. 2011

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

131

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“…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). …”

Section: Introductionmentioning

confidence: 99%

7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide

et al. 2012

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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.

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“…7-Chloro-4-suIfobenzofurazan, also known as Sbf-chloride, is a non-fluorescent water-soluble analogue of Nbf(NBD) chloride. Whereas S-Nbf derivatives are much less fluorescent than N-Nbf derivatives (Ghosh et al, 1981), the converse is true for the corresponding Sbf derivatives. Thus Sbf-chloride can be used to selectively determine thiols, amidst other biological nucleophiles, with the considerable sensitivity of a fluorirnetric assay (Andrews et al, 1982).…”

Section: Department Of Clinical Pharmacology Flinders University Bementioning

confidence: 94%

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

1982

Clin Exp Pharmacol Physiol

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Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a n active compound found in many peppers, is believed to reduce the effectiveness of some cutaneous stimuli by impairing the function of sensory nerves, particularly those containing substance P. In the present work, an indirect immunohistochemical method has been used to localize substance P-like immunoreactivity in nerves associated with the cardiovascular system in the guinea-pig. It was found that reactive nerves were present throughout the system. The larger arteries, the pericardium, cardiac valves and the vena cava near the heart were all densely supplied. In general, the numbers of positive nerves decreased as smaller vessels were approached.Guinea-pigs were injected subcutaneously with capsaicin (Sigma). The drug was administered in a carrier made up of 50% ethanol and 50% Tween 80. For long-term effects to be examined, the injections were given in increasing doses (25, 50, 100, 200 and 400 mg/kg on five successive days) and the animals taken at from 2 to 61 days after the final injection. Guinea-pigs were also examined at from 2 h to 10 days after a single injection of capsaicin (50 mg/kg). At 2 h the intensity of reaction of fibres was slightly reduced. This reduction in intensity continued up to 24 h. At 12 h many swollen, distorted axons were seen; their appearance was similar to axons after axotomy or chemical toxins. At 24 h very few fibres with substance P-like immunoreactivity were detected. In the longer term experiments, depletion of substance P was found to persist up to 61 days.These results suggest that substance P fibres in the cardiovascular system are sensory. The presence and distribution of neuropeptides inthe autonomic ganglia which supply pelvic viscera in the guinea-pig. M. Costa, J. B. Furness, D. Mayor and R. Papka (introduced by P. Me fin), The distribution of substance P, vasoactive intestinal polypeptide (VIP), enkephalin and somatostatin immunoreactivity in the anterior and posterior pelvic plexuses was investigated by using an immunohistochemical technique applied to whole mounts. In all the small ganglia present along the hypogastric nerve and in the pelvic plexuses substance P immunoreactive fibres formed both a loose network throughout the ganglia and some well defined baskets around 0305-1870/82/0800-0389 $02.00 0 1982 Blackwell Scientific Publications 389Abstracts ganglion cell bodies. In the ganglia of these plexuses a significant proportion of nerve cell bodies showed substance P immunoreactivity. Following treatment with capsaicin the immunoreactivity of the loose ganglionic network and of a large proportion of nerve fibres in the nerve bundles of the plexus and of the hypogastric ganglia disappeared while the substance P immunoreactive ganglion cells and the pericellular baskets were not affected. Numerous ganglion cells in these plexuses showed VIP immunoreactivity and in the ganglia varicose nerve fibres formed pericellular baskets around non-immunoreactive ganglion cells. Large numbers of immunoreactive fibres were als...

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Benzofurazans and benzofuroxans: Biochemical and pharmacological properties

Cited by 74 publications

References 97 publications

Molecular structure, vibrational, UV and NBO analysis of 4-chloro-7-nitrobenzofurazan by DFT calculations

Molecular structure, vibrational, UV and NBO analysis of 4-chloro-7-nitrobenzofurazan by DFT calculations

7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

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