Abstract
Mithramycin is an antitumor compound produced by Streptomyces argillaceus that has been used for the treatment of several types of tumors and hypercalcaemia processes. However, its use in humans has been limited because of its side effects. Using combinatorial biosynthesis approaches, we have generated seven new mithramycin derivatives, which differ from the parental compound in the sugar profile or in both the sugar profile and the 3-side chain. From these studies three novel derivatives were identified, demycarosyl-3D-β-D-digitoxosylmithramycin SK, demycarosylmithramycin SDK, and demycarosyl-3D-β-D-digitoxosylmithramycin SDK, which show high antitumor activity. The first one, which combines two structural features previously found to improve pharmacological behavior, was generated following two different strategies, and it showed less toxicity than mithramycin. Preliminary in vivo evaluation of its antitumor activity through hollow fiber assays, and in subcutaneous colon and melanoma cancers xenografts models, suggests that demycarosyl-3D-β-D-digitoxosylmithramycin SK could be a promising antitumor agent worthy of further investigation.
| Original language | English |
|---|---|
| Pages (from-to) | 5813-5825 |
| Number of pages | 13 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 55 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 28 2012 |
Funding
| Funders | Funder number |
|---|---|
| National Childhood Cancer Registry – National Cancer Institute | R01CA102102 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
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