Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents

Organic & Biomolecular Chemistry
Sergey E SosonyukNikolay S Zefirov

Abstract

Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents.

References

May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·G H HockermanW A Catterall
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Nov 9, 2001·Journal of Molecular Biology·J LöweE Nogales
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN
Jun 19, 2004·Bioorganic & Medicinal Chemistry Letters·S ChandrasekharG Narahari Sastry
Jul 29, 2004·Current Medicinal Chemistry·David J Newman, Gordon M Cragg
Mar 4, 2005·The Biochemical Journal·P J BrittoJ Wolff
Mar 30, 2005·Chemical Communications : Chem Comm·Gary C H ChiangAndrew B Holmes
Dec 15, 2010·European Journal of Medicinal Chemistry·Andrey E ShchekotikhinMaria N Preobrazhenskaya
Feb 18, 2011·Journal of Chemical Information and Modeling·Mark McGann
Mar 8, 2011·Medicinal Research Reviews·Richard A StantonRitu Aneja
Jul 26, 2011·Bioorganic & Medicinal Chemistry·Fabrice BerruéRussell G Kerr
Jun 7, 2012·Journal of Computer-aided Molecular Design·Mark McGann
Jul 12, 2013·Chembiochem : a European Journal of Chemical Biology·Olga N ZefirovaSergei A Kuznetsov
Jul 24, 2014·Accounts of Chemical Research·David G I Kingston, James P Snyder
Dec 10, 2017·European Journal of Medicinal Chemistry·Ya-Nan CaoXian-Li Zhou

❮ Previous
Next ❯

Citations

Feb 12, 2021·Natural Product Reports·Anthony R CarrollMichèle R Prinsep

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
acylation
column chromatography
NMR

Software Mentioned

OMEGA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.