Synthesis and Structure-Activity Relationships of Novel Ecdysteroid Dioxolanes as MDR Modulators in Cancer
Open accessAbstract
Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal bioactivities in mammals, including humans. In a previous study, we have found a significant effect of certain derivatives on the ABCB1 transporter mediated multi-drug resistance of a transfected murine leukemia cell line. In this paper, we present a structure-activity relationship study focused on the apolar dioxolane derivatives of 20-hydroxyecdysone. Semi-synthesis and bioactivity of a total of 32 ecdysteroids, including 20 new compounds, is presented, supplemented with their complete 1H- and 13C-NMR signal assignment.
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Apolar substituents on the 2,3-diol moiety of ecdysteroids are more important than those at positions 20 and 22 for the anticancer activity.
“After several further studies, exploring this particular anticancer activity of ecdysteroids, we now know that 1) apolar substituents on the 2,3-diol moiety are more important than those at positions 20 and 22 [19]”
From Nitrogen-containing ecdysteroid derivatives vs. multi-drug resistance in cancer: Preparation and antitumor activity of oximes, oxime ethers and a lactam (2018) · cites this paper as [19]
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Cites
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“The most abundant representative of these compounds, 20-hydroxyecdysone (20E), regulates the reproduction, embryogenesis, diapause and molting of arthropods [1].”
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Ecdysteroids: Production in plant in vitro cultures
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“Compounds 13–36were synthesized as published before (Martins et al., 2013, 2012; (Balazs et al., 2013), and their chemical structures including the stereochemistry of asymmetrically substituted 20,22- and 2,3;20,22-dioxolanes were determined by comprehensive one- and two-dimensional NMR techniques…”
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“Moreover, compound 2 was deduced to be the same ecdysteroid compound 29α-(3-methoxy-4-hydroxyphenyl)-20,22-O-methylidene-20-hydroxyecdysone recently reported in the literature (Martins et al. 2013), by comparison of its spectroscopic data with reported values.”
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“Martins et al. [63] studied the SAR of the apolar dioxolane derivatives of 20-hydrox-yecdysone Martins et al. [63] studied the SAR of the apolar dioxolane derivatives of 20-hydroxyecdysone The results showed that the substituted dioxolane ring at the 2,3 position is far more important for strong…”
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In Vitro Production of Steroids
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Preparation of bioactive oxidized ecdysteroid derivatives
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- Authors
- Martins, A., Csábi, J., Balázs, A., Kitka, D., Amaral, L., Molnár, J., Simon, A., Tóth, G., & Hunyadi, A.
- Affiliations
- University of Szeged (HU)
- Ubichem Research Ltd., Illatos út 33, Budapest H-1097, Hungary
- Universidade Nova de Lisboa (PT)
- Budapest University of Technology and Economics (HU)
- Corresponding author
- Martins, Ana
- Hunyadi, Attila
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2013-12-10
- Volume
- 18
- Issue
- 12
- Pages
- 15255-15275
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC6269874
- OpenAlex
- W2016988911
- Cited by
- 30
- References
- 17
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 1
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (2010-0012)
- Fundação para a Ciência e a Tecnologia (SFRH/BPD/81118/2011, PEst-OE/SAU/UI0074/2011)
- European Social Fund (TÁMOP 4.2.2/B-10/1-2010-0012, 4.2.2.A-11/1/KONV-2012-0035)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- ecdysteroids, dioxolanes, 20-hydroxyecdysone, multidrug resistance, structure-activity relationship, semisynthesis, NMR resonance assignment, cancer chemotherapy
- MeSH terms
- Animals, Antineoplastic Agents, Dioxolanes, Doxorubicin, Drug Synergism, Lymphoma, Neoplasms, Structure-Activity Relationship, Molecular Structure, ATP Binding Cassette Transporter, Subfamily B, Nuclear Magnetic Resonance, Biomolecular, Inhibitory Concentration 50, Combinatorial Chemistry Techniques, Ecdysteroids, Cell Line, Tumor, Cell Proliferation, Mice
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