Combinatorial Synthesis to Identify a Potent, Necrosis-Inducing Rhenium Anticancer Agent

Inorganic Chemistry
Chilaluck C KonkankitJustin J Wilson

Abstract

Combinatorial synthesis can be applied for developing a library of compounds that can be rapidly screened for biological activity. Here, we report the application of microwave-assisted combinatorial chemistry for the synthesis of 80 rhenium(I) tricarbonyl complexes bearing diimine ligands. This library was evaluated for anticancer activity in three different cancer cell lines, enabling the identification of three lead compounds with cancer cell growth-inhibitory activities of less than 10 μM. These three lead structures, Re-9B, Re-9C, and Re-9D, were synthesized independently and fully characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray crystallography. The most potent of these three complexes, Re-9D, was further explored to understand its mechanism of action. Complex Re-9D is equally effective in both wild-type and cisplatin-resistant A2780 ovarian cancer cells, indicating that it circumvents cisplatin resistance. This compound was also shown to possess promising activity against ovarian cancer tumor spheroids. Additionally, flow cytometry showed that Re-9D does not induce cell cycle arrest or flipping of phosphatidylserine to the outer cell membrane. Analysis of the morphological changes of can...Continue Reading

References

Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A K GodwinM E Anderson
Mar 1, 1997·Bioorganic & Medicinal Chemistry·H Maehr
Jul 29, 1998·Chemico-biological Interactions·H H Bailey
Dec 29, 2000·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·C J ZieglerS J Lippard
Nov 17, 2001·Seminars in Nuclear Medicine·S BanerjeeN Ramamoorthy
Oct 16, 2002·Journal of Chemical Information and Computer Sciences·Igor V Tetko, Vsevolod Yu Tanchuk
Aug 22, 2003·Nature·Alison Abbott
Oct 8, 2003·Current Pharmaceutical Design·M GalanskiB K Keppler
Jun 3, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeany M Rademaker-LakhaiJan H M Schellens
Sep 24, 2004·Cell Biochemistry and Function·Ganesaratnam K BalendiranDeborah Fraser
Dec 8, 2004·Current Topics in Medicinal Chemistry·Enzo AlessioGianni Sava
Feb 16, 2005·Apoptosis : an International Journal on Programmed Cell Death·S RelloA Villanueva
Mar 7, 2006·Critical Reviews in Clinical Laboratory Sciences·José M EstrelaElena Obrador
Dec 8, 2006·Journal of Medicinal Chemistry·Brian K Shoichet
Feb 3, 2007·Anti-cancer Agents in Medicinal Chemistry·Victoria CepedaJose M Pérez
Feb 23, 2007·Archiv der Pharmazie·Ingo Ott, Ronald Gust
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lainie P MartinRussell J Schilder
Feb 14, 2009·Nature Protocols·Juergen FriedrichLeoni A Kunz-Schughart
Dec 17, 2009·Cell Death and Differentiation·T Vanden BergheP Vandenabeele
Jan 13, 2010·Journal of Oncology·Kimio Ushijima
Mar 3, 2010·Annual Review of Biophysics·Peter A Leventis, Sergio Grinstein
Aug 7, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·Seann P MulcahyEric Meggers
Oct 28, 2010·Journal of Medicinal Chemistry·Ying FuPeter J Sadler
Nov 17, 2010·Journal of Medicinal Chemistry·Gilles GasserNils Metzler-Nolte
Mar 15, 2011·Metallomics : Integrated Biometal Science·Michael GroesslPaul J Dyson
Apr 2, 2011·Current Protocols in Cytometry·Zbigniew Darzynkiewicz
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Maame Efua S SampahRobert F Siliciano
May 5, 2012·Journal of the American Chemical Society·Brock S HowertonEdith C Glazer
Nov 10, 2012·Journal of the American Chemical Society·Alexis C KomorJacqueline K Barton
Jul 25, 2013·Inorganic Chemistry·Isolda Romero-Canelón, Peter J Sadler
Sep 10, 2013·Nature Chemical Biology·Mohammad Fallahi-SichaniPeter K Sorger
Jan 1, 2011·Cancers·Angel L OrtegaJose M Estrela
Apr 25, 2014·Journal of Biomolecular Screening·Angelika WalzlHelmut Dolznig
Jul 25, 2014·European Journal of Pharmacology·Shaloam Dasari, Paul Bernard Tchounwou
Aug 20, 2014·ACS Chemical Biology·Anna Leonidova, Gilles Gasser
Nov 8, 2014·Chemistry : a European Journal·Sylvain Clède, Clotilde Policar

❮ Previous
Next ❯

Citations

Sep 3, 2019·Current Pharmaceutical Design·Philippe ColleryVeena Vijaykumar
May 16, 2019·Chemistry : a European Journal·A Paden KingJustin J Wilson
Apr 23, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Chilaluck C KonkankitJustin J Wilson
May 15, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Thines KanagasundaramKlaus Kopka
May 21, 2020·Chemical Communications : Chem Comm·Chilaluck C KonkankitJustin J Wilson
May 13, 2020·Angewandte Chemie·Sierra C MarkerJustin J Wilson

❮ 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.