Antiproliferative drug

Percutaneous coronary intervention A minimally invasive procedure whereby access to the coronary arteries is obtained through the femoral artery up the aorta to the coronary os. Contrast media is used to visualize the coronary artery stenosis using a coronary angiogram. A guidewire is used to cross the stenosis and a small balloon is inflated and/or stent is deployed to break up atherosclerotic plaque and restore coronary artery blood flow. The stent is left in place to prevent acute closure and restenosis of the coronary artery. Newer stents are coated with antiproliferative drugs, such as paclitaxel and sirolimus, which further reduce the risk of restenosis of the coronary artery. 

Levitzki, A. and Gilon, C. (1991). Tyrphostins as molecular tools and potential antiproliferative drugs. TiPS 12, 171 174. 

Kirmani M, Santana M, Sorgente N, Wiedemann P, Ryan SJ. Antiproliferative drugs in the treatment of experimental proliferative vitreoretinopathy. Retina 1983 3 269-272. 

With the aim to overcome the excessive VSMC proliferation observed after BMS implantation, devices able to locally deliver antiproliferative drugs (drug-eluting stents [DESs]) have been developed (Figure 15.21). The most used antiproliferative drugs are sirolimus (Rapamycin ) and paclitaxel (Taxol ). The delivery of these antiproliferative drugs from DES reduces artery restenosis (down to 5%-10% of treated patients [211,212]) more efficiently than BMS. However, DESs did not completely solve the problem [213] as they can trigger unwanted side effects such as stent thrombosis (ST) and delayed restenosis compared to BMS [214,215]. 

Lanza, G.M., Yu, X., Winter, P.M., Abendschein, D.R., Karukstis, K.K., Scott, M.J., et al. Targeted antiproliferative drug dehvery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent implications for rational therapy of restenosis. Circulation 106, 2842-2877 (2002)... 

Namitharan and Pitchnmani (2011) proposed a novel Cu-catalyzed one-pot sul-fonyl azide-alkyne/ketenimine-nitrone cycloaddition sequence for the synthesis of imidazolidin-4-ones, which might be utilized as antimalarial and antiproliferative drugs. The heterogeneous version employing Cu(I)-zeolites as recyclable catalysts is attractive for its improved efficiency and diastereoselectivity (Scheme 4.54). In this case, a three-component heterogeneous domino process was utilized and a variety of imidazolidin-4-ones were synthesized in moderate to excellent yields. The products could be easily isolated by simple filtration. 

The use of PHA coatings to enhance biocompatibility of vascular stents was shown to be an effective modification. Self-expanding nitinol mesh vascular stents were coated with PHA and PHA loaded with an antiproliferative drug. Stents were placed in the femoral artery of dogs and examined for 120 days. The analysis of the state of the vessels and morphometric examination showed the effectiveness of coating vascular stents with PHA, especially PHA loaded with an antiproliferative drug. Reactive changes in the vessel wall were less pronounced and no complications occurred that are usually caused by implantation of uncoated metal stents (Protopopov et al. 2005, 2008). 

Sirohmus and everolimus are new antiproliferative drugs that have successfully been used after liver and kidney transplantation. However, little data are available regarding the treatment of BOS with these therapies in lung transplantation. The available data suggests that addition of rapamycin may arrest the decline of FEVi and may, at least in some patients, improve the FEV] (47,48). In one recent study, everolimus seemed to prevent the decline in FEV], at least one year after the introduction, but this effect was lost in the next year later (49). TLI and ECP may also reduce the speed of FEV] decline, without producing major side effects (50,51). 

Sustained delivery of antiproliferative drugs to prevent in-stent restenosis is crucial for an ideal biodegradable polymeric stent. However, the drugs (sirolimus and paclitaxel) that are most commonly used in currently available DES systems are both lipophilic. The hydrophilic nature of chitosan matrices makes them unable to entrap poorly soluble therapeutic agents and greatly limits their range of applications as drug delivery systems. A consistent limitation of... 

Midtkandal et al reported a facile and new synthetic route to a C-nucleoside, 2-deo>y benzamide riboside (21). The synthesised target was found to be active against a number of cancer cell lines. Similar ribose-based C-nucleosides are known as antiviral and antiproliferative drugs, such as formycin, tiazofurin and benzamide riboside. 

---