Alkaloids in Future Drug Discovery

Ferreira, Maria José Umbelino

doi:10.3390/molecules27041347

Cited by 17 publications

(8 citation statements)

References 12 publications

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“…Additionally, aporphine alkaloids (anonaine, dicentrinone, and liriodenine), moupinamide, and methylferulate have shown anti‐inflammatory 66,76,77 and hypotensive activity 78 that could reduce the effects of T2DM and metabolic syndrome. Undoubtedly, alkaloids from natural sources are an important group of compounds to discover new therapeutic agents 79 . However, only two alkaloids are currently in clinical trials for managing T2DM 3 .…”

Section: Resultsmentioning

confidence: 99%

“…Undoubtedly, alkaloids from natural sources are an important group of compounds to discover new therapeutic agents. 79 However, only two alkaloids are currently in clinical trials for managing T2DM. 3 Therefore, future works should be directed towards broad studies (in vitro and in vivo assays) that allow an approach to search for new drugs from natural sources or to suggest candidate molecules for semi-synthesis.…”

Section: Estimation Of Enzyme Activity and Antioxidant Capacitymentioning

confidence: 99%

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Application of effect‐directed analysis using TLC–bioautography for rapid isolation and identification of antidiabetic compounds from the leaves of Annona cherimola Mill.

Galarce‐Bustos,

Obregón,

Vallejos‐Almirall

et al. 2023

Phytochemical Analysis

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IntroductionType 2 diabetes mellitus is a globally prevalent chronic disease characterised by hyperglycaemia and oxidative stress. The search for new natural bioactive compounds that contribute to controlling this condition and the application of analytical methodologies that facilitate rapid detection and identification are important challenges for science. Annona cherimola Mill. is an important source of aporphine alkaloids with many bioactivities.ObjectiveThe aim of this study is to isolate and identify antidiabetic compounds from alkaloid extracts with α‐glucosidase and α‐amylase inhibitory activity from A. cherimola Mill. leaves using an effect‐directed analysis by thin‐layer chromatography (TLC)–bioautography.MethodologyGuided fractionation for α‐glucosidase and α‐amylase inhibitors in leaf extracts was done using TLC–bioassays. The micro‐preparative TLC was used to isolate the active compounds, and the identification was performed by mass spectrometry associated with web‐based molecular networks. Additionally, in vitro estimation of the inhibitory activity and antioxidant capacity was performed in the isolated compounds.ResultsFive alkaloids (liriodenine, dicentrinone, N‐methylnuciferine, anonaine, and moupinamide) and two non‐alkaloid compounds (3‐methoxybenzenepropanoic acid and methylferulate) with inhibitory activity were isolated and identified using a combination of simple methodologies. Anonaine, moupinamide, and methylferulate showed promising results with an outstanding inhibitory activity against both enzymes and antioxidant capacity that could contribute to controlling redox imbalance.ConclusionsThese high‐throughput methodologies enabled a rapid isolation and identification of seven compounds with potential antidiabetic activity. To our knowledge, the estimated inhibitory activity of dicentrinone, N‐methylnuciferine, and anonaine against α‐glucosidase and α‐amylase is reported here for the first time.

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Section: Resultsmentioning

confidence: 99%

Section: Estimation Of Enzyme Activity and Antioxidant Capacitymentioning

confidence: 99%

Application of effect‐directed analysis using TLC–bioautography for rapid isolation and identification of antidiabetic compounds from the leaves of Annona cherimola Mill.

Galarce‐Bustos,

Obregón,

Vallejos‐Almirall

et al. 2023

Phytochemical Analysis

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“…Plant-derived alkaloids are nitrogen-containing organic compounds that can be utilized to treat a variety of diseases, including cancer (Ferreira, 2022). The basic pharmacokinetic properties of the most well-known alkaloids are analgesic and anti-inflammatory.…”

Section: Discussionmentioning

confidence: 99%

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine

Abdali,

Nadipour Borujeni,

Hosseini

et al. 2024

Cell Biology International

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The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP‐binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug‐metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds.

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“…A decline in the cholinergic depots of the body weakens the memory, whereas some plants have been found to reinstate the cholinergic level and thus improve memory [ 46 ]. A number of plants have been reported to have promising anticholinesterase potential in the form of extracts and isolated metabolites [ 47 , 48 , 49 ]. Unfortunately, AD is becoming more prevalent day by day and efforts on a huge scale are needed to discover novel drugs with prominent anti-Alzheimer potential.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

et al. 2022

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Salvia moorcroftiana is medicinally used in various parts of the world to treat a number of diseases. In the literature, the antiamnesic activity of this plant has not yet been reported. Therefore, the current study was aimed at evaluating the in vivo antiamnesic (scopolamine-induced) potential of Salvia moorcroftiana. The major phytochemical groups such as total phenolic (TPC), total tannin (TTC), and total flavonoid content (TFC) in methanolic extract (SlMo-Crd) and subsequent fractions of Salvia moorcroftiana were quantified using standard methods. The in vitro anticholinesterase (against butyryl cholinesterase; BChE and acetylcholinesterase; AChE) and antioxidant (against 2,2-diphenyl-1-picrylhydrazyl; DPPH and 2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ABTS free radicals) potentials of crude (SIMO-Crd) extract and fractions (hexane; SlMo-Hex, chloroform; SlMo-Chl, ethyl acetate; SlMo-Et) were also determined. The SlMo-Crd at doses of 100 and 200 mg/kg body weight compared to fractions of 75 and 150 mg/kg body weight (which were 1/10th of the highest dose tested in acute toxicity tests) were evaluated for their memory enhancement and learning behavior in normal and scopolamine-induced mental dysfunction in mice using behavioral memory tests such as the Y-maze test and novel object recognition test (NORT). Moreover, the samples were further evaluated for acetylcholine contents and biochemical markers such as MDA (malondialdehyde), SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione peroxidase) levels. The maximum TPC with a value of 114.81 ± 1.15 mg GAE/g, TTC with a value of 106.79 ± 1.07 mg GAE/g, and TFC with a value of 194.29 ± 0.83 mg RE/g were recorded for the SlMo-Chl fraction. Against the DPPH free radical, the methanolic extract exhibited an IC50 value of 95.29 ± 1.06 µg/mL whereas, among the fractions, the best activity was observed for the SlMo-Chl fraction with an IC50 of 75.02 ± 0.91 µg/mL, followed by SlMoS-Et with an IC50 value of 88.71 ± 0.87 µg/mL. Among the extracts, the SlMo-Chl and SlMo-Et fractions inverted the amnesic effects of scopolamine in mice effectively. Additionally, the SlMo-Chl and SIMO-Et fractions considerably enhanced the percent spontaneous alteration performance in the Y-maze test with values of 65.18 ± 2.61/69.51 ± 2.71 and 54.92 ± 2.49/60.41 ± 2.69, respectively, for the tested doses. The discrimination index (DI) in experimental mice was considerably enhanced by the SlMo-Chl in the NORT with values of 59.81 ± 1.21/61.22 ± 1.31% DI correspondingly for the tested doses, as mentioned above, followed by the SlMo-Et extract. The selected plant in the form of extracts ameliorated the effects of amnesia in mice and could, therefore, be used as a therapy for amnesia; however, this is subject to further exploration in other animal models and the isolation of the responsible compounds.

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Alkaloids in Future Drug Discovery

Abstract: Alkaloids are nitrogen-containing compounds, biosynthesized by both marine and terrestrial organisms, often with strong biological properties [...]

Cited by 17 publications

References 12 publications

Application of effect‐directed analysis using TLC–bioautography for rapid isolation and identification of antidiabetic compounds from the leaves of Annona cherimola Mill.

Application of effect‐directed analysis using TLC–bioautography for rapid isolation and identification of antidiabetic compounds from the leaves of Annona cherimola Mill.

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine

Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana

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