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Tuning of Ruthenium – DMSO Complexes for Search of New Anticancer Agents
Published in Ajay Kumar Mishra, Lallan Mishra, Ruthenium Chemistry, 2018
The interest in metal-based chemotherapeutic agents originated in the early 1970s with the serendipitous discovery of cisplatin by Rosenberg (Rosenberg, 1969), and it became world’s first selling anticancer drug. It showed the inhibition of the division of bacterial cells and mainly used in the treatment of metastatic testicular, ovarian, and transitional bladder cancer (Kelland, 2007). Several promising metal-based chemotherapeutic agents have been extensively studied after the discovery of cisplatin (Allardyce, 2016). After cisplatin, nearly 40 platinum-based agents have been designed and investigated clinically as anticancer agents. These include carboplatin, oxaliplatin, and satraplatin. Generally, platinum-based complexes (cisplatin and carboplatin) inhibit DNA synthesis through covalent binding of DNA molecules to form intrastrand and interstrand DNA cross-links. However, oxaliplatin showed a different mechanism of action as its bulky diaminocyclohexane carrier ligand activates oxaliplatin and form platinum-DNA adduct, which blocks the DNA replication and turns out to be more cytotoxic (Alcindor, 2011). At present, octahedral platinum(IV) complex satraplatin is the most promising as applied orally due to its kinetic inertness in advanced clinical stage (Bhargava, 2009). Despite several efforts of current platinum-based drugs, they were found effective only to a limited range of cancerous cells. Some cancerous cells attain intrinsic resistance and these drugs have severe side effects such as gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), renal tubular injury, neuromuscular complications, and ototoxicity. Therefore, there is still a need to design new approaches to outwit these drawbacks (Jakupec, 2003). Among transition metal complexes, octahedral ruthenium complexes are found appealing candidates in the search for new diagnostic and therapeutic agents (Erkkila, 1999).
Spectrophotometric and physicochemical studies on the interaction of a new platinum(IV) complex containing the drug pregabalin with calf thymus DNA
Published in Journal of Coordination Chemistry, 2020
Nahid Shahabadi, Sara Amiri, Hossein Zhaleh
As regards that DNA (deoxyribonucleic acid) is known as one of the primary targets for many drugs including metal-based anticancer ones that are usually in clinical use or in advanced clinical trials, in order to develop such new metal-based therapeutics, the binding mechanisms of metal complexes to DNA should be studied. Similarly to cisplatin, satraplatin as a platinum(IV) complex can act through the formation of DNA-crosslinks, DNA-distortion, and subsequent inhibition of DNA-transcription and replication. The ability of satraplatin to overcome cisplatin resistance is thought to arise from the asymmetric nature of the DNA-lesions, which unlike cisplatin adducts, can evade recognition by DNA repair proteins [18–20]. Platinum(IV) complexes can platinate DNA in their oxidized form, but the formation of cytotoxic lesions via ligand substitution requires weeks to complete [21].
Human serum albumin binding studies of a new platinum(IV) complex containing the drug pregabalin: experimental and computational methods
Published in Journal of Coordination Chemistry, 2019
Nahid Shahabadi, Sara Amiri, Avat (Arman) Taherpour
Satraplatin has potent growth inhibition on several human cancers both in vitro and in small-animal models. In small-cell lung cancer cell lines, satraplatin has a 50% inhibitory concentration in the submicromolar range, equivalent to or less than that of cis-platin [8]. That shares some structural similarities with cis-platin but also has important differences. Satraplatin inhibited the growth of cervical cancer cell lines, including those resistant to cis-platin [9]. The oral route of administration and the intermittent schedule makes it very convenient for clinical use [10].