Stobadine: Bellwether of a broader view of drug actions

Vincenzi, Frank F.; Hinds, Thomas R.

doi:10.1016/s0024-3205(99)00438-5

Cited by 8 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Štolc et al [ 9 ] introduced a synthetic indole compound stobadine—(–)-cis-2,8-dimethyl- -2,3,4,4a,5,9b-hexahydro-1 H -pyrido[4,3b]indole (( 3 ) in Figure 1 )—which can be classified as an optically active form of the clinically used racemic drug carbidine [ 10 ]. Stobadine, along with cardioprotective, neuroprotective, antihistamine, and antiulcerous effects, demonstrates antioxidative and free-radical scavenging properties [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Valachová

Mach

Šoltés

2020

IJMS

View full text Add to dashboard Cite

Indole derivatives such as isatin (a natural compound), cemtirestat, stobadine, and its derivatives (synthetic compounds) are known to have numerous positive effects on human health due to regulation of oxidative status. The aim of the study was to assess radical scavenging capacities of these compounds and explore their potential protective effects against reactive oxygen species formed during Cu(II) ions and ascorbate-induced degradation of high-molar-mass hyaluronan. Based on the IC50 values determined by the ABTS assay, the most effective compound was SM1M3EC2·HCl reaching the value ≈ 11 µmol/L. The lowest IC50 value reached in the DPPH assay was reported for cemtirestat ≈ 3 µmol/L. Great potency of inhibition of hyaluronan degradation was shown by cemtirestat, followed by isatin even at low concentration 10 µmol/L. On the other hand, stobadine·2HCl had also a protective effect on hyaluronan degradation, however at greater concentrations compared to cemtirestat or isatin. SME1i-ProC2·HCl reported to be a less effective compound and SM1M3EC2·HCl can be considered almost ineffective compared to stobadine·2HCl. In conclusion, our results showed that both isatin and cemtirestat were capable of attenuating the degradation of high-molar-mass hyaluronan due to their ability to complex/sequester cupric ions.

show abstract

Section: Introductionmentioning

confidence: 99%

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Valachová

Mach

Šoltés

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Indoles such as serotonin, melatonin, tryptophan, indole-3-carbinol, pyridoindoles, etc., occur endogenously and/or in many plants, and may comprise a family of radical scavengers ( 4 ) . It has been suggested that some pharmacological effects of particular indoles result from their antioxidant properties ( 5 , 6 ) . Serotonin hydroxycinnamic acid amides (e.g.…”

mentioning

confidence: 99%

Effects of safflower seed extract supplementation on oxidation and cardiovascular risk markers in healthy human volunteers

et al. 2008

View full text Add to dashboard Cite

We previously demonstrated that safflower seed extract (SSE) and its major antioxidant constituents, serotonin hydroxycinnamic acid amides, suppressed LDL oxidation in vitro, decreased plasma autoantibody titres to oxidized LDL and attenuated atherosclerotic lesion formation in apoE-deficient mice. In this report, we examined whether SSE, rich in serotonin derivatives, could affect markers of oxidative stress, inflammation and aortic stiffness in healthy human subjects. Twenty Japanese male volunteers were studied at baseline, after 2·1 g SSE supplementation daily (providing 290 mg serotonin derivatives/d) for 4 weeks, and after a 4-week washout period. Significant reductions in circulating oxidized LDL, autoantibody titres to malondialdehyde-modified LDL, the soluble form of vascular cell adhesion molecule-1 (sVCAM-1), and urinary 8-isoprostane were observed after a 4-week intervention. Although there were no statistically significant differences in blood pressure or brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, baPWV was lower than baseline in eleven of twenty subjects and was accompanied by a reduction in blood pressure. Statistically significant negative correlations were observed between the extent of initial cardiovascular risk markers (autoantibody titres, 8-isoprostane, sVCAM-1 and baPWV) and the effect of intervention. This suggested that individuals with elevated oxidative stress, inflammation, and/or arterial stiffness may receive more benefit from SSE supplementation.

show abstract

“…The pyridoindole stobadine is a compound with an array of pharmacological actions, among which the antioxidant, free radical scavenging, and tissue protecting actions are dominant (Vincenzi and Hinds, 1999; see also monothematic issue of Life Sci. 65, No.…”

Section: Introductionmentioning

confidence: 99%

Development of the New Group of Indole-Derived Neuroprotective Drugs Affecting Oxidative Stress

et al. 2006

View full text Add to dashboard Cite

1. The role of oxidative stress, and accordingly uncontrolled reactive oxygen species generation/action, have been widely documented in a number of different neuronal pathologies. However, the concept of pharmacological interventions in prevention and therapy of oxidative stress-related diseases has not found adequate application in clinical practice. This may be due to the insufficient efficacy of drugs available, their unsuitable pharmacokinetics, side effects, toxicity, etc. 2. Based on stobadine, (--)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole, a well-known antioxidant, free radical scavenger, and neuroprotectant, it was attempted to develop new stobadine derivatives with improved pharmacodynamic and toxicity profiles, on applying molecular design, synthesis and adequate tests. Stobadine molecule was modified mostly by electron donating substitution on the benzene ring and by alkoxycarbonyl substitution at N-2 position. A total of >70 derivatives were prepared. 3. In a mice model of head trauma, some of the new stobadine derivatives administered i.v. immediately after the trauma, significantly improved sensomotoric outcome in the animals assessed 1 h later. Accordingly, decrease in brain edema was proved histologically as well as by brain wet weight assessment. 4. Putative neuroprotective action of the compounds was confirmed on rat hippocampal slices exposed to reversible 6 min hypoxia/low glucose by analysis of synaptic transmission in CA1 region neurons. Irreversible impairment of neurotransmission resulting from the hypoxia was significantly reduced by the presence of SMe1EC2, one of the new compounds, in concentration range 0.03-10.0x10(-6) mol l(-1). Both the neuroprotective and antioxidant effect of the compound closely resembled those of stobadine, melatonin, 21-aminosteroids, alpha-phenyl-tert-butylnitrone and others, all well-established antioxidants, except the range of effective concentrations was by 1-2 orders lower in SMe1EC2. 5. A remarkable antioxidant efficacy was observed in the new compounds in rat brain homogenates exposed to iron/ascorbate system by protection of lipids and creatine kinase against the oxidative impairment. A link between the neuroprotective and antioxidant/ scavenger properties in the compounds can be assumed. 6. Acute toxicity of some of the new pyridoindoles was diminished compared to stobadine. That might be due to the virtually full elimination of stobadine's undesired alpha (1)-adrenolytic activity attained by appropriate modifications of its molecule. 7. The new pyridoindoles extend the range of available neuroprotectants interfering with oxidative stress in neuronal tissue.

show abstract

Stobadine: Bellwether of a broader view of drug actions

Cited by 8 publications

References 44 publications

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Effects of safflower seed extract supplementation on oxidation and cardiovascular risk markers in healthy human volunteers

Development of the New Group of Indole-Derived Neuroprotective Drugs Affecting Oxidative Stress

Contact Info

Product

Resources

About