Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics

Coy-Barrera, Ericsson; Ogungbe, Ifedayo Victor; Schmidt, Thomas J.

doi:10.3390/molecules28093690

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…Natural products exhibit an enormous range of structural and chemical diversity, and in particular, small organic molecules derived from nature demonstrate significant translational potential [ 46 , 47 ]. This is ascribed to the remarkable ability of living organisms to synthesize elaborate molecules with well-defined properties in biological systems, and climacostol serving as a demonstrative example of a small molecule.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly Drosophila melanogaster

Catalani,

Brunetti,

Del Quondam

et al. 2024

Toxics

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The ciliate Climacostomum virens produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly Drosophila melanogaster to evaluate how the xenobiotic climacostol affects biological systems in vivo at the organismal level. Food administration with climacostol demonstrated its harmful role during larvae developmental stages but not pupation. The midgut of eclosed larvae showed apoptosis and increased generation of reactive oxygen species (ROS), thus demonstrating gastrointestinal toxicity. Climacostol did not affect enteroendocrine cell proliferation, suggesting moderate damage that does not initiate the repairing program. The fact that climacostol increased brain ROS and inhibited the proliferation of neural cells revealed a systemic (neurotoxic) role of this harmful substance. In this line, we found lower expression of relevant antioxidant enzymes in the larvae and impaired mitochondrial activity. Adult offsprings presented no major alterations in survival and mobility, as well the absence of abnormal phenotypes. However, mitochondrial activity and oviposition behavior was somewhat affected, indicating the chronic toxicity of climacostol, which continues moderately until adult stages. These results revealed for the first time the detrimental role of ingested climacostol in a non-target multicellular organism.

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Section: Discussionmentioning

confidence: 99%

Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly Drosophila melanogaster

Catalani,

Brunetti,

Del Quondam

et al. 2024

Toxics

View full text Add to dashboard Cite

show abstract

“…Numerous NPs in nature contain a variety of effective and complex small molecules that play a key role in drug discovery ( Atanasov et al, 2021 , Coy-Barrera et al, 2023 ). These small molecules include alkaloids, phenylpropanoids, quinones, flavonoids, terpenoids, steroids, organic acids, amino acids, and microelements.…”

Section: Natural Small Moleculesmentioning

confidence: 99%

Recognition on pharmacodynamic ingredients of natural products

Wang,

Fu,

et al. 2024

Saudi Pharmaceutical Journal

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Structural variety and pharmacological potential of naphthylisoquinoline alkaloids

Feineis,

Bringmann

2024

The Alkaloids: Chemistry and Biology

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Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics

Abstract: Natural products (NPs) from plants, fungi, animals, and microorganisms have historically played important roles in drug discovery [...]

Cited by 5 publications

References 17 publications

Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly Drosophila melanogaster

Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly Drosophila melanogaster

Recognition on pharmacodynamic ingredients of natural products

Structural variety and pharmacological potential of naphthylisoquinoline alkaloids

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