Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library

Bioorg Chem. 2021 Jun 30;115:105135. doi: 10.1016/j.bioorg.2021.105135. Online ahead of print.ABSTRACTNoscapine 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.PMID:34303039 | DOI:10.1016/j.bioorg.2021.105135

Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Faezeh Nemati Iris Bischoff-Kont Peyman Salehi Samad Nejad-Ebrahimi Maryam Mohebbi Morteza Bararjanian Nasim Hadian Zahra Hassanpour Yvonne Jung Sofie Schaerlaekens Daniel Lucena-Agell Mar ía A Oliva Robert F ürst Hamid R Nasiri Source Type: research