Status of Bi- and Multi-Nuclear Platinum Anticancer Drug Development

Abstract

Cisplatin has become one of the most commonly used compounds for the treatment of a wide spectrum of human malignancies. Unfortunately, cisplatin has several major drawbacks. Driven by the impressive impact of cisplatin on cancer chemotherapy, great efforts have been made to develop new derivatives with improved pharmacological properties. Among the over 30 platinum agents which have entered clinical trials after the onset of clinical studies with cisplatin in the early 1970s, only carboplatin and oxaliplatin have received worldwide approval so far, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval. It has become quite evident that mere analogues of cisplatin or carboplatin will not probably offer any substantial clinical advantages over the existing drugs. Therefore, people turned to synthesize non-classical platinum anticancer drugs which were capable of forming a different range of DNA adducts which could display a different spectrum of anticancer activity compared to cisplatin. This review will summarize the structural types and structure-activity rules of non-classical bi- and multi-nuclear platinum anticancer drugs, and discuss their future potential as anticancer agents.

Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells

“…Cisplatin has been used for the treatment of a variety of human cancers including testicular, ovarian, bladder, breast, cervical, stomach, head and neck, prostate, esophageal, sarcoma, and neuroblastoma 60–62. However, the current research findings including genes’ transcriptional alterations (Table 1), inhibition of cell cycle progression (Fig.…”

A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

“…[10][11][12] Despite all these drawbacks, the first-line chemotherapy for 12 different neoplasms with more than 50% of clinically applied anticancer regimens contains a platinum(II)-based compound. [13][14][15] Considering all the mentioned facts, our idea was to design new Pt-based anticancer compounds containing ligands which already exert biological properties expecting synergistic effects. 16 Several 8-hydroxyquinolines (hqH) are already known for their antimicrobial and antiprotozoal activity and many of them are or were used in clinical practice.…”

Synergistic protective effect of <em>N</em>-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats

“…Platinum-based chemotherapeutic agents, including cisplatin (cis-diaminedichloroplat-inum II; CDDP), are widely used for the treatment of a broad spectrum of cancers 1. However, the clinical use of CDDP is limited because of its high incidence of toxicity, mainly nephrotoxicity 2.…”