Design and synthesis of heterobimetallic topoisomerase I and II inhibitor complexes: in vitro DNA binding, interaction with 5'-GMP and 5'-TMP and cleavage studies

Journal of Photochemistry and Photobiology. B, Biology
Farukh Arjmand, Mohd Muddassir

Abstract

New potential cancer chemotherapeutic complexes Cu-Sn(2)/Zn-Sn(2) 3 and 4 were designed and prepared as topoisomerases inhibitors; their in vitro DNA binding studies were carried out which reveal strong electrostatic binding via phosphate backbone of DNA helix, in addition to other binding modes viz. coordinate covalent and partial intercalation. To throw insight to molecular binding event at the target site, UV-vis titrations of 3 and 4 with mononucleotides of interest, viz, 5'-GMP and 5'-TMP were carried out, (in case of 4) by (1)H and (31)P NMR. Cleavage studies employing gel electrophoresis demonstrate both the complexes 3 and 4 are efficient cleavage agents and are specific groove binders (complex 3 binds to both major and minor groove while complex 4 is specifically minor groove binder only). In addition, the complexes show high inhibition activity against topoisomerase I and II. However, complex 4 exhibits significant inhibitory effects on the Topo I activity at a very low concentration approximately 2.5 microM.

References

Jun 12, 1992·Annals of the New York Academy of Sciences·E B Keverne, K M Kendrick
Dec 1, 1984·The Science of the Total Environment·S S Ranade, V K Panday
Jan 1, 1996·Annual Review of Biochemistry·J C Wang
Sep 28, 1998·Biochimica Et Biophysica Acta·Y PommierD Strumberg
Dec 4, 1998·Bioscience, Biotechnology, and Biochemistry·K SuzukiM Uyeda
Jun 1, 2000·Journal of Inorganic Biochemistry·E KikutaE Kimura
Nov 16, 2001·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·G D LiuR Q Yu
Oct 2, 2002·Bioscience, Biotechnology, and Biochemistry·Keitarou Suzuki, Masaru Uyeda
May 10, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Marta González-AlvarezBernard Meunier
Apr 6, 2004·Current Opinion in Chemical Biology·Janet R Morrow, Olga Iranzo
Apr 20, 2004·Biochemical and Biophysical Research Communications·Mark A BaileyDeclan P Naughton
Jun 3, 2005·Biological & Pharmaceutical Bulletin·Krzysztof BielawskiSławomir Wołczyński
Sep 30, 2005·Chemical Communications : Chem Comm·Takeo ItoSteven E Rokita
Aug 2, 2006·Bioorganic & Medicinal Chemistry·Mari Sithambaram KarthikeyanNalilu Suchetha Kumari
Mar 27, 2007·Journal of Inorganic Biochemistry·Arturo SilvestriVincenzo Turco Liveri
May 29, 2007·European Journal of Medicinal Chemistry·Deepa SinhaAnil K Mishra
Aug 8, 2007·Mutation Research·A Kathleen McClendon, Neil Osheroff
Jan 2, 2008·Inorganic Chemistry·Azadeh LalehzariChristopher J Levy
Aug 30, 2008·Biomacromolecules·C N N'soukpoé-KossiH A Tajmir-Riahi
Jan 16, 2009·The Journal of Physical Chemistry. B·David CharbonneauHeidar-Ali Tajmir-Riahi
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Sep 30, 2009·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Hoi-Ling SengChew-Hee Ng
Dec 22, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Yan-Cheng LiuChris Orvig
Dec 22, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Zhen-Feng ChenChris Orvig
Feb 13, 2010·The Journal of Physical Chemistry. B·P BourassaH A Tajmir-Riahi

❮ Previous
Next ❯

Citations

Jul 28, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Hoi-Ling SengChew-Hee Ng
Jul 23, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Mohammad Taghi BehnamfarMona Salimi
Jul 25, 2012·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Lee-Fang ChinChew-Hee Ng
Jul 1, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Ruma Dey GhoshSoumitra K Choudhuri
Aug 13, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sze-Tin VonChew-Hee Ng
Aug 23, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jun-Feng KouLiang-Nian Ji
Oct 16, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·Kejie DuHui Chao
Jan 25, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Shiva MehranZafar Gholinejad

❮ 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.