Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library
| Autor: | Zahra Hassanpour, Sofie Schaerlaekens, Hamid R. Nasiri, Samad Nejad-Ebrahimi, María A. Oliva, Morteza Bararjanian, Faezeh Nemati, Maryam Mohebbi, Yvonne Jung, Robert Fürst, Daniel Lucena-Agell, Nasim Hadian, Peyman Salehi, Iris Bischoff-Kont |
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| Přispěvatelé: | Iranian National Science Foundation, Shahid Beheshti University, Consejo Superior de Investigaciones Científicas (España), Bischoff-Kont, Iris [0000-0002-2057-0604], Salehi, Peyman [0000-0001-5774-3372], Nejad-Ebrahimi, Samad [0000-0003-2167-8032], Bararjanian, Morteza [0000-0003-2235-9877], Schaerlaekens, Sofie [0000-0002-4410-2311], Lucena-Agell, Daniel [0000-0001-7314-8696], Oliva, María A. [0000-0002-2215-4639], Fürst, Robert [0000-0002-9926-7578], Bischoff-Kont, Iris, Salehi, Peyman, Nejad-Ebrahimi, Samad, Bararjanian, Morteza, Schaerlaekens, Sofie, Lucena-Agell, Daniel, Oliva, María A., Fürst, Robert |
| Rok vydání: | 2021 |
| Předmět: |
Noscapine
Drug repurposing Antineoplastic Agents Huisgen reaction Opium Poppy 01 natural sciences Biochemistry Natural product Phthalide Tubulin binding Small Molecule Libraries HeLa chemistry.chemical_compound Tubulin Cell Line Tumor Drug Discovery medicine Humans Papaver Isoquinoline Molecular Biology Benzofurans Cell Proliferation biology 010405 organic chemistry Cell growth Tubulin-binding Organic Chemistry Isoquinolines biology.organism_classification 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Drug Design Anticancer agents Protein Binding medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 53 p.-7 fig.-1 tab.-1 schem.-1 graph. abst. Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine. We are also grateful to the Iran National Science Foundation (INSF, grant number 98026465) for financial support of this project and Shahid Beheshti University Research Council for providing facilities of to conduct this study. This work was supported by CSIC PIE 201920E111 (MAO). |
| Databáze: | OpenAIRE |
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