Design, synthesis, theoretical calculations and biological evaluation of new non-symmetrical choline kinase inhibitors

European Journal of Medicinal Chemistry
Belén Rubio-RuizAntonio Entrena

Abstract

Inhibition of Choline Kinase (ChoK) has been reported as a therapeutical target in the treatment of some kinds of tumor. In this paper, the design and synthesis of new non-symmetrical monocationic ChoK inhibitors is described, bearing a cationic head and an adenine moiety connected by linkers of different lengths. Docking studies indicate that the cationic head of these compounds could be inserted into the choline binding site of the enzyme, while the adenine moiety could be stabilized into the ATP binding site. Docking studies also support the difference of activity of the synthesized compounds, which depends on both the substituent at position 4 of the cationic head and the linker length, being dimethylamine and 1,4-diphenylbutane respectively, the most appropriate ones. Compounds 14 (IC(50) = 10.70 ± 0.40 μM) and 17 (IC(50) = 6.21 ± 0.97 μM) are the most potent ChoK inhibitors and suitable for further modification with a view to obtain more potent antitumor compounds.

References

Dec 11, 1997·Oncogene·R Hernández-AlcocebaJ C Lacal
Aug 15, 2002·Biochemical and Biophysical Research Communications·Ana Ramírez de MolinaJuan Lacal
Sep 17, 2002·European Journal of Biochemistry·José M Jiménez-LópezCarmen Marco
Aug 9, 2003·Journal of Medicinal Chemistry·Ana Conejo-GarcíaAntonio Espinosa
Oct 25, 2003·The Journal of Organic Chemistry·Ana Conejo-GarcíaAntonio Espinosa
Mar 9, 2004·Progress in Lipid Research·Chieko AoyamaKozo Ishidate
Mar 12, 2004·Cancer Letters·Ana Ramírez de MolinaJuan Carlos Lacal
Jul 2, 2005·The Journal of Organic Chemistry·Ana Conejo-GarcíaAntonio Espinosa
Jul 5, 2005·Cancer Research·Ana Ramírez de MolinaJuan Carlos Lacal
May 25, 2006·Current Medicinal Chemistry·S JanardhanG Narahari Sastry
Jan 20, 2007·International Journal of Cancer. Journal International Du Cancer·Galit EliyahuHadassa Degani
Dec 17, 2008·Current Cancer Drug Targets·Mónica Bañez-CoronelJuan Carlos Lacal

❮ Previous
Next ❯

Citations

Dec 5, 2014·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·A Estévez-BraunJ C Lacal
Feb 26, 2016·European Journal of Medicinal Chemistry·Sahil SharmaKunal Nepali
Aug 5, 2014·European Journal of Medicinal Chemistry·Belén Rubio-RuizAna Conejo-García
Apr 16, 2015·Future Medicinal Chemistry·Francisco Fermín Castro-NavasLuisa Carlota López-Cara
Jul 26, 2018·Future Medicinal Chemistry·Gianluca RubbiniLuisa Carlota López-Cara
Apr 25, 2012·Magnetic Resonance in Chemistry : MRC·Belén Rubio-RuizAntonio Entrena
Jun 12, 2014·Magnetic Resonance in Chemistry : MRC·Belén Rubio-RuizAna Conejo-García
Oct 31, 2013·Magnetic Resonance in Chemistry : MRC·Santiago Schiaffino-OrtegaAntonio Entrena
Jul 3, 2013·Chembiochem : a European Journal of Chemical Biology·María Sahún-RonceroRamon Hurtado-Guerrero
Mar 27, 2019·Scientific Reports·Alberto Sola-LeyvaMaría P Carrasco-Jiménez
Oct 27, 2020·Medicinal Research Reviews·Belén Rubio-RuizAna Conejo-García

❮ Previous
Next ❯

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.