Reexploring 5-methoxyindole-2-carboxylic acid (MICA) as a potential antidiabetic agent

Lv, Yan

doi:10.2147/dmso.s166485

Cited by 9 publications

(3 citation statements)

References 25 publications

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“…Information is also lacking on the metabolites enclosed in square brackets in Scheme 1 . Like PAG, they may have appreciable blood levels and they may be pharmacologically active since one of them is 5-methoxyindole-3-carboxylic acid, a positional isomer of 5-methoxyindole-2-carboxylic acid, that is a potent hypoglycemic agent [ 115 ].…”

Section: Tegaserod and Ibs-cmentioning

confidence: 99%

Tegaserod for the Treatment of Irritable Bowel Syndrome

Madia

Messore

Saccoliti

et al. 2020

AIAAMC

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Background: Tegaserod (Zelnorm®) is a 5-hydroxytryptamine (serotonin) type 4 receptor agonist for the treatment of hypomotility disorders of the lower gastrointestinal tract associated with the irritable bowel syndrome with constipation (IBS-C). Objective: The authors provide the reader with a better understanding on tegaserod mechanism of action, on its pharmacodynamics and pharmacokinetic properties, on safety and tolerability, with a summary of the key published clinical trials conducted in patients with IBS. Its effects on colon inflammation have also been described. Results: Tegaserod was withdrawn in 2007 due to increased risks of cardiovascular adverse effects. The manufacturer denied this, because pre-existing cardiovascular disease or risk factors were attributed to all affected patients. Thus, no causal relationship between tegaserod use and cardiovascular events was clearly shown. A matched case-control study of tegaserod-treated with untreated patients found no association between tegaserod and adverse cardiovascular outcomes. Despite its adverse effects, tegaserod resulted to be effective in treating chronic constipation in adult women aged < 65 years with IBS-C, while the safety and effectiveness of tegaserod in men with IBS-C have not been established. Tegaserod was resubmitted to the Food and Drug Administration in 2018 for use in a low-risk population. Moreover, tegaserod has also been shown to improve symptoms, enhance gastric accommodation and significantly attenuate visceral pain arising from the colon in functional dyspepsia patients. Treatment with tegaserod seems also to exert a protective effect in inflamed colons, reducing the severity of colitis in animal models.

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Section: Tegaserod and Ibs-cmentioning

confidence: 99%

Tegaserod for the Treatment of Irritable Bowel Syndrome

Madia

Messore

Saccoliti

et al. 2020

AIAAMC

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“…Currently, there are two DLDH inhibitors that have been studied. One is MICA [69], and the other is valproic acid (VPA) metabolites. As we have covered MICA in above discussions, we would now discuss VPA metabolites.…”

Section: Potential Dldh Inhibitorsmentioning

confidence: 99%

Chronic Inhibition of Mitochondrial Dihydrolipoamide Dehydrogenase (DLDH) as an Approach to Managing Diabetic Oxidative Stress

Song

Yan

2019

Antioxidants

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Mitochondrial dihydrolipoamide dehydrogenase (DLDH) is a redox enzyme involved in decarboxylation of pyruvate to form acetyl-CoA during the cascade of glucose metabolism and mitochondrial adenine triphosphate (ATP) production. Depending on physiological or pathophysiological conditions, DLDH can either enhance or attenuate the production of reactive oxygen species (ROS) and reactive nitrogen species. Recent research in our laboratory has demonstrated that inhibition of DLDH induced antioxidative responses and could serve as a protective approach against oxidative stress in stroke injury. In this perspective article, we postulated that chronic inhibition of DLDH could also attenuate oxidative stress in type 2 diabetes. We discussed DLDH-involving mitochondrial metabolic pathways and metabolic intermediates that could accumulate upon DLDH inhibition and their corresponding roles in abrogating oxidative stress in diabetes. We also discussed a couple of DLDH inhibitors that could be tested in animal models of type 2 diabetes. It is our belief that DLDH inhibition could be a novel approach to fighting type 2 diabetes.

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“…Increased concentrations of ester glucuronides and sulfates from compounds related to MI2CA have been observed in patients with advanced melanoma [10]. Moreover, MI2CA and its derivatives show promising potential in the treatment of diabetes [11].…”

Section: Introductionmentioning

confidence: 99%

Discovery of a New Polymorph of 5-Methoxy-1H-Indole-2-Carboxylic Acid: Characterization by X-ray Diffraction, Infrared Spectroscopy, and DFT Calculations

Polak,

Bąkowicz,

Morzyk-Ociepa

2024

Molecules

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This study presents a new 5-methoxy-1H-indole-2-carboxylic acid (MI2CA) polymorph investigated by single-crystal X-ray diffraction, infrared spectroscopy, and density functional theory (ωB97X-D) calculations employing two basis sets (6-31++G(d,p) and aug-cc-pVTZ). The compound crystallizes in the monoclinic system, space group P21/c (a = 4.0305(2) Å, b = 13.0346(6) Å, c = 17.2042(9) Å, β = 91.871(5)°, Z = 4). In the crystalline structure, the formation of cyclic dimers via double hydrogen bonds O−H⋯O between MI2CA molecules was observed. Interactions between the NH groups of the indole rings and the adjacent methoxy groups, as well as C–H⋯O contacts, significantly influence the spatial arrangement of molecules. The results from DFT calculations, including dimeric and trimeric structures, agree well with the experimental structural and spectroscopic data. Analysis of the infrared spectra confirms the conclusions drawn from X-ray diffraction studies and reveals differences between the IR spectra of the newly obtained polymorph and that reported earlier in the literature. This comprehensive study sheds some light on the MI2CA polymorphism and is important for a potential pharmacological applications of this compound.

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Reexploring 5-methoxyindole-2-carboxylic acid (MICA) as a potential antidiabetic agent

Cited by 9 publications

References 25 publications

Tegaserod for the Treatment of Irritable Bowel Syndrome

Tegaserod for the Treatment of Irritable Bowel Syndrome

Chronic Inhibition of Mitochondrial Dihydrolipoamide Dehydrogenase (DLDH) as an Approach to Managing Diabetic Oxidative Stress

Discovery of a New Polymorph of 5-Methoxy-1H-Indole-2-Carboxylic Acid: Characterization by X-ray Diffraction, Infrared Spectroscopy, and DFT Calculations

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