(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones

Autor: Mauricio Cuellar, Joan Villena, Natalia Quiñones, Santiago Hernández, Cristian O. Salas, Iván Brito, Alan R. Cabrera, Luis Espinoza Catalán
Rok vydání: 2018
Předmět:
Colorectal cancer
Stereochemistry
Cell Survival
angucyclinone derivatives
Pharmaceutical Science
Anthraquinones
Antineoplastic Agents
Shikimic Acid
010402 general chemistry
01 natural sciences
Article
Analytical Chemistry
lcsh:QD241-441
Prostate cancer
chemistry.chemical_compound
Structure-Activity Relationship
(-)-Shikimic acid
lcsh:Organic chemistry
Cell Line
Tumor
Drug Discovery
medicine
Cytotoxic T cell
Potency
Humans
Physical and Theoretical Chemistry
Cytotoxicity
Cell Proliferation
cancer cell lines
Cycloaddition Reaction
Molecular Structure
010405 organic chemistry
Chemistry
Organic Chemistry
Shikimic acid
medicine.disease
In vitro
0104 chemical sciences
hetero-Diels-Alder
Chemistry (miscellaneous)
Cell culture
MCF-7 Cells
Molecular Medicine
cytotoxicity
Drug Screening Assays
Antitumor
HT29 Cells
Zdroj: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules, Vol 23, Iss 6, p 1422 (2018)
Molecules
Volume 23
Issue 6
ISSN: 1420-3049
Popis: We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC50 values (less than 10 &mu
M), especially for the most sensitive cells, PC-3 and HT-29. From a chemical point of view, depending on the protected group of ring A and the pattern of substitution on ring D, cytotoxicity elicited these compounds, in terms of their potency and selectivity. Therefore, according to these chemical features, the most promising agents for every cancer cell line were 7a, 17, and 19c for PC-3 cells
7a, 17, and 20 for HT-29 cells, and 19a for MCF-7 cells.
Databáze: OpenAIRE
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