Cytotoxicity of New Damsin Derivatives in Breast Cancer Cells
(2019) In Journal of Pharmacy & Drug Development 1(2).- Abstract
- As a follow-up of a previous investigation in which semisynthetic damsin derivatives were shown to possess up to 10 times higher cytoxicity in JIMT-1 breast cancer cells compared to normal breast epithelial MCF-10A cells, a range of new derivatives were prepared and assayed toward the same cells. Damsin, a natural plant metabolite containing a α-methylene-γ-lactone (or 3-methylenedihydro- furan-2(3H)-one) moiety, was modified in position 3 by Claisen-Schmidt condensations with aromatic aldehydes, mainly mono- or disubstituted benzaldehydes, without affecting the α-methylene-γ-lactone function. This lactone ring is a Michael acceptor that is known to affect biological processes such as cell proliferation, death/apoptosis, and cell... (More)
- As a follow-up of a previous investigation in which semisynthetic damsin derivatives were shown to possess up to 10 times higher cytoxicity in JIMT-1 breast cancer cells compared to normal breast epithelial MCF-10A cells, a range of new derivatives were prepared and assayed toward the same cells. Damsin, a natural plant metabolite containing a α-methylene-γ-lactone (or 3-methylenedihydro- furan-2(3H)-one) moiety, was modified in position 3 by Claisen-Schmidt condensations with aromatic aldehydes, mainly mono- or disubstituted benzaldehydes, without affecting the α-methylene-γ-lactone function. This lactone ring is a Michael acceptor that is known to affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with nucleophilic sites in cell signalling pathways. However, although Michael acceptors are reactive, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate the binding to and the release from any given nucleophilic site in a protein, and thereby moderate a specific biological activity. In this investigation, the cytotoxicity of 20 α-methylene-γ-lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared, by determining the inhibitory concentration 50 (IC50) from dose response curves. The IC50 values in the two cell lines were found to depend on the overall structure of the assayed compounds, although less in this subset of compounds compared to a previous investigation. Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4684702d-6afe-4bb9-9bf5-2ead4fa6aea5
- author
- Lozano, Maribel LU ; Soria, Wendy LU ; Manner, Sophie LU ; Oredsson, Stina LU ; Villagomez, Juan R V LU and Sterner, Olov LU
- contributor
- Almanza, Giovanna
- organization
- publishing date
- 2019-08-27
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- MCF-10A, JIMT-1, Semisynthesis, α-methylene-γ-lactones, Michael acceptors, SAR:s
- in
- Journal of Pharmacy & Drug Development
- volume
- 1
- issue
- 2
- pages
- 19 pages
- publisher
- Annex Publishers
- ISSN
- 2348-9782
- language
- English
- LU publication?
- yes
- id
- 4684702d-6afe-4bb9-9bf5-2ead4fa6aea5
- alternative location
- https://escientificpublishers.com/cytotoxicity-of-new-damsin-derivatives-in-breast-cancer-cells-JPDD-01-0011
- date added to LUP
- 2019-11-27 11:21:22
- date last changed
- 2021-05-18 08:18:54
@article{4684702d-6afe-4bb9-9bf5-2ead4fa6aea5, abstract = {{As a follow-up of a previous investigation in which semisynthetic damsin derivatives were shown to possess up to 10 times higher cytoxicity in JIMT-1 breast cancer cells compared to normal breast epithelial MCF-10A cells, a range of new derivatives were prepared and assayed toward the same cells. Damsin, a natural plant metabolite containing a α-methylene-γ-lactone (or 3-methylenedihydro- furan-2(3H)-one) moiety, was modified in position 3 by Claisen-Schmidt condensations with aromatic aldehydes, mainly mono- or disubstituted benzaldehydes, without affecting the α-methylene-γ-lactone function. This lactone ring is a Michael acceptor that is known to affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with nucleophilic sites in cell signalling pathways. However, although Michael acceptors are reactive, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate the binding to and the release from any given nucleophilic site in a protein, and thereby moderate a specific biological activity. In this investigation, the cytotoxicity of 20 α-methylene-γ-lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared, by determining the inhibitory concentration 50 (IC50) from dose response curves. The IC50 values in the two cell lines were found to depend on the overall structure of the assayed compounds, although less in this subset of compounds compared to a previous investigation. Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed.}}, author = {{Lozano, Maribel and Soria, Wendy and Manner, Sophie and Oredsson, Stina and Villagomez, Juan R V and Sterner, Olov}}, issn = {{2348-9782}}, keywords = {{MCF-10A; JIMT-1; Semisynthesis; α-methylene-γ-lactones; Michael acceptors; SAR:s}}, language = {{eng}}, month = {{08}}, number = {{2}}, publisher = {{Annex Publishers}}, series = {{Journal of Pharmacy & Drug Development}}, title = {{Cytotoxicity of New Damsin Derivatives in Breast Cancer Cells}}, url = {{https://escientificpublishers.com/cytotoxicity-of-new-damsin-derivatives-in-breast-cancer-cells-JPDD-01-0011}}, volume = {{1}}, year = {{2019}}, }