Narrow Results

The serendipitous discovery of the antitumor properties of cisplatin by Barnett Rosenberg some forty years ago brought about a paradigm shift in the field of medicinal chemistry and challenged conventional thinking regarding the role of potentially toxic heavy metals in drugs. Platinum(II)-based anticancer drugs have since become some of the most effective and widely-used drugs in a clinician's arsenal and have saved countless lives. However, they are limited by high toxicity, severe side-effects and the incidence of drug resistance. In recent years, attention has shifted to stable platinum(IV) complexes as anticancer prodrugs. By exploiting the unique chemical and structural attributes of their scaffolds, these platinum(IV) prodrugs offer new strategies of targeting and killing cancer cells. This review summarizes the development of anticancer platinum(IV) prodrugs to date and some of the exciting strategies that utilise the platinum(IV) construct as targeted chemotherapeutic agents against cancer.

In this paper, the cisplatin composite micro/nanofibers were prepared by electrospinning. Average diameter of the typical products was about 700 nm, and cisplatins were incorporated in biodegradable poly (L-lactic acid) fibers. The controlled release of cisplatin can be gained for long time. The possible mechanisms of cisplatin release in the PBS and the PBS with proteinase K were discussed. 3-(4, 5)-dimethylthiahiazo-(-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) method was used to test antitumor activities in vitro against human lung tumor spc-a-1 cells. When incubation time was 24 h, the same content of cisplatin from virgin cisplatin and the composite fibers has almost equal antitumor activity in vitro. However, when incubation time was 48 h, the composite fibers show much higher antitumor activity than the virgin cisplatin. The system may be useful in the postoperative local chemotherapy and have clinical applications as an implantable drug for tumor in the future.

The adsorption of cisplatin on pristine monolayer graphene (MLG), pristine bilayer graphene (BLG) and Al-doped BLG (Al-BLG) was investigated using density functional theory. The obtained results showed that pristine MLG and pristine BLG were not sensitive to cisplatin. Adsorption energy can be primarily influenced by the atomic species rather than the adsorption position. Moreover, it is strong chemisorption of hollow-site Al-BLG (H-Al-BLG) toward cisplatin. The most stable configurations are the Pt or Cl atom interaction with the Al atom of H-Al-BLG. In conclusion, H-Al-BLG is a kind of potential high quality delivery carrier for anticancer cisplatin.

A series of nanoscale-level metal complexes with bidentate (N₂MCl${}_2)$ and tetradentate (MN) chromophores have been employed as efficient cisplatin analogues and intercalating agents towards DNA and studied their anticancer activities against A549 cancer cells. Among them, complexes 1–6 exist with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which have been found to bind covalently with herring sperm DNA. Complexes 7–12 may undergo an intercalative mode of binding due to their structural differences relative to 1–6. The intrinsic binding constants obtained for complexes 7–12 were also significantly varied due to their structure and binding mode ($0.95-1.6\times 10^5$ and $1.5-2.4\times 10^4$ M${}^{-1}$ for complexes, 1–3 and 4–6, respectively). However, complexes 7–9 have shown much stronger binding constants ($0.98-1.64\times 10^6$ M${}^{-1}$) due to their existing planarity which leads them to strong intercalation than their counterparts, 10–12 ($3.19-4.14\times 10^4$ M${}^{-1}$). The significantly higher binding constant values for complexes 1–3 may due to their planar structure and also may possibly lead to intercalation. Though all these complexes (1–12) have shown almost similar binding constants (1.26–2.0) in the electrochemical analysis, it implies that these complexes interact towards DNA with equal strength at their reduced oxidation (M${}^{+I}$) states. The obtained results in various spectral, electrochemical, relative viscosity changes, DNA cleavage studies revealed that these complexes 1–6 mimic the functional properties of cisplatin. Therefore, these nanostructured complexes could be substituted for cisplatin as a new family of non-platinum-based anticancer drugs in the future, after a sequence of in-vivo investigation. Their potential activity against A549 cancer cells has also been recorded using Hoechst staining and Propidium iodide images.