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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).
Spectroscopy, docking and molecular dynamics studies on the interaction between cis and trans palladium-alanine complexes with calf-thymus DNA and antitumor activities
Published in Journal of Coordination Chemistry, 2023
Asma Izadyar, Hassan Mansouri-Torshizi, Effat Dehghanian, Somaye Shahraki
Cisplatin (cis-diaminedichloroplatinum(II)) is one of the important anticancer drugs and was first discovered in 1960s by Rosenberg [1]. It has widespread use in treatment of some types of human tumors such as genitourinary tumors. However, the resistance of cancer cells and undesirable side effects limited its application [2]. Among the clinical side effects of using cisplatin are nephrotoxicity and hepatotoxicity [3]. Another platinum-based drug which has fewer side effects than cisplatin, used as a second generation drug, was made by replacing chlorides of cisplatin by two carboxylate groups is carboplatin [4]. This compound has a similar mechanism of action as cisplatin but less side effects which may be due to chelate effects. Oxaliplatin is a third-generation platinum-based anticancer drug usually used in the treatment of colorectal cancer [1]. Platinum complexes as effective drugs in the treatment of cancers has attracted attention and researchers have shown that the nature of ligands coordinated to platinum can affect how the drug works and are metabolized within the cell [4]. Thus, focuses are on designing new metal complexes with various ligands with improved pharmacological properties [5].
Schiff base complexes, cancer cell lines, and anticancer evaluation: a review
Published in Journal of Coordination Chemistry, 2022
Sheikh Abdul Majid, Jan Mohammad Mir, Gowhar Jan, Aabid Hussain Shalla
Due to the chemotherapeutic action of cisplatin, there have been developments of other metal complexes having anticancer activity [6]. Compounds related to cisplatin such as oxaliplatin/carboplatin are used around the globe for cancer treatment [7]. However, several side effects are exhibited by these drugs such as toxicity and drug resistance limiting their clinical use [8–10]. These limitations need to be overcome by exploring new Schiff base ligands for treatment of cancer. Studies from the last ten years are reported in this review. The synthesized drugs have been evaluated for anticancer activity both in vivo and in vitro. Schiff base ligands show different denticity in forming metal complexes and have versatile applications towards anticancer and antimicrobial activity due to the azomethine group [11–13].
Tetrazolo[1,5-a]pyrimidine-based metal(II) complexes as therapeutic agents: DNA interaction, targeting topoisomerase I and cyclin-dependent kinase studies
Published in Inorganic and Nano-Metal Chemistry, 2018
Azees Khan Haleel, Dharmasivam Mahendiran, Ummer Muhammed Rafi, Vijaykumar Veena, Sugumar Shobana, Aziz Kalilur Rahiman
Transition metal complexes having the ability to bind and cleave double stranded DNA, thereby changing the replication of DNA and inhibiting the growth of tumor cells, which is the basis for designing new and more efficient antitumor drugs.[1] The platinum based drugs are widely and effectively used as anticancer agents. Cisplatin is used as an anticancer agent for the treatment of testicular and ovarian cancers. Carboplatin is used extensively for lung cancer cell. Oxaliplatin has recently been used for the treatment of colorectal cancer. A large portion (in the range of 65% to 98%) of cisplatin and its derivatives carboplatin and oxaliplatin bind to protein and enzyme of blood plasma within a day after intravenous administration, which is believed to be the cause of several severe side effects like ototoxicity, nephrotoxicity etc.[2] As a result, it is essential to design metal complexes with less toxic, target-specific and with non-covalent binding mode to DNA. To develop such kind of anticancer drugs, it is necessary to understand different non-covalent binding modes of metal complexes with DNA, i.e. binding along the outside of the helix, binding along the major and/or minor grooves, and intercalation of a planar molecule or a planar aromatic ring system between base pairs. The planarity, coordination geometry and type of donor atom present in ligands play a key role in determining the intercalating ability of complexes to bind DNA.[3,4] Unlike intercalators, groove binders must have flexible structures; this sort of binding implies insertion of the drug into the grooves of the double, triple helices, causing a distortion of the DNA backbone smaller than that caused by intercalation.[5] Currently, minor groove binders are used in development of DNA sequence selective binding agents because they are prone to modulate the gene expression, due to their high significant affinity and base-pair specificity. However, minor grooves often have the benefit of being free and may afford available room to bind small molecules. Most of the antibiotic and anticancer drugs are small molecules; hence the main binding site is in the minor grove of DNA.[6]