Ecdysteroids as Potent Enzyme Inhibitors and Verification of Their Activity Using In Vitro and In Silico Docking Studies
Open accessAbstract
Ecdysteroids represent arthropods’ steroidal hormones, and they exist in about 5–6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri-O-acetate (4) showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E (7) with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide (18) (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E (7) showed the best ranking score with a docking score of −5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential.
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20E can exert in vitro inhibition on activities of acetylcholinesterase, butirylcholinesterase, tyrosinase, and α-amylase.
“20E also can exert in vitro inhibition on activities of pharmacologically important enzymes like acetylcholinesterase, butirylcholinesterase, tyrosinase, and α-amylase not in disagreement with the complexity of the hormone action [93].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [93]
Methods §2.1 identifies 20-hydroxyecdysone (20E) as one of the compounds tested, and §3.2 reports in vitro inhibition of the four enzymes by tested ecdysteroids. The results passages do not establish that unmodified 20E inhibited all four; several highlighted effects are from other ecdysteroids or 20E derivatives. Page numbers were not available in our copy. (LLM, conf=0.83)
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- Authors
- Mamadalieva, N. Z., Hussain, H., Mollica, A., Zengin, G., Mamadalieva, R. Z., Elhady, S. S., Fadil, S. A., Ashour, M. L., & Youssef, F. S.
- Affiliations
- Academy of Sciences Republic of Uzbekistan (UZ)
- Leibniz Institute of Plant Biochemistry (DE)
- University of Chieti-Pescara (IT)
- Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey
- Kokand State Pedagogical Institute named after Mukimi (UZ)
- King Abdulaziz University (SA)
- Ain Shams University (EG)
- Corresponding author
- Mamadalieva, Nilufar Z.
- Ashour, Mohamed L.
- ORCID
- Venue
- Life
- Publisher
- MDPI AG
- Published
- 2022-05-31
- Volume
- 12
- Issue
- 6
- Pages
- 824
- ISSN
- 2075-1729 (ISSN-L)
- PMC
- PMC9225039
- OpenAlex
- W4281787929
- Cited by
- 7
- References
- 29
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Life (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU) (RG-23-166-43)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Keywords
- ecdysteroids, enzyme inhibition, acetylcholinesterase, butyrylcholinesterase, tyrosinase, alpha-amylase, molecular docking, ADMET prediction, TOPKAT, principal component analysis, anticholinergic agents, antidiabetic drugs
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