MyJournals Home  

RSS FeedsMolecules, Vol. 25, Pages 362: New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation (Molecules)


15 january 2020 21:02:39

Molecules, Vol. 25, Pages 362: New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation (Molecules)

Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to β-tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability. More importantly, conversion of its chemically fragile side chain into a stabilized bioisostere is envisioned to enable zampanolide to possess more drug-like properties. As part of our ongoing project aiming to develop its mimics with a stable side chain using straightforward synthetic approaches, 2-fluorobenzyl alcohol was designed as a bioisosteric surrogate for the side chain based on its binding conformation as confirmed by the X-ray structure of tubulin complexed with zampanolide. Two new zampanolide mimics with the newly designed side chain have been successfully synthesized through a 25-step chemical transformation for each. Yamaguchi esterification and intramolecular Horner–Wadsworth–Emmons condensation were used as key reactions to construct the lactone core. The chiral centers at C17 and C18 were introduced by the Sharpless asymmetric dihydroxylation. Our WST-1 cell proliferation assay data in both docetaxel-resistant and docetaxel-naive prostate cancer cell lines revealed that compound 6 is the optimal mimic and the newly designed side chain can serve as a bioisostere for the chemically fragile N-acetyl hemiaminal side chain in zampanolide.

70 viewsCategory: Biochemistry, Chemistry, Molecular Biology
Molecules, Vol. 25, Pages 341: Casticin Induces DNA Damage and Affects DNA Repair Associated Protein Expression in Human Lung Cancer A549 Cells (Running Title: Casticin Induces DNA Damage in Lung Cancer Cells) (Molecules)
Molecules, Vol. 25, Pages 361: Synthesis of Elaborate Benzofuran-2-carboxamide Derivatives through a Combination of 8-Aminoquinoline Directed C-H Arylation and Transamidation Chemistry (Molecules)
blog comments powered by Disqus
The latest issues of all your favorite science journals on one page


Register | Retrieve


Molecular Biology

Copyright © 2008 - 2020 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Nachrichten