Anticancer drugs, potential

Chapter 4 - Propolis has been used for as a traditional medicine in Eastern Europe as an antifungal, antimicrobial, antiviral, anti-inflammatory, and anticarcinogenic agent. The author isolated three cinamic acid derivatives and one flavanol derivative from Brazilian propolis and determined their structures by spectroscopic analysis. Results were assayed, the anticancer drug potential of these compounds to identify new drug candidates, by determining the... 

The unusual tolyporphin was isolated from the Pacific cyanophyte Tolypothrix nodosa and it has been shown that tolyporphin eliminates the multidrug resistance (MDR) in certain carcinoma sublines thus potentiating the cytotoxicity of anticancer drugs in these cell lines.2... 

In comparison with the intravenous route of administration the potential advantages of intraperitoneal therapy are the avoidance of high toxic drug plasma levels and an increased (local) exposure of tumors (cells) to anticancer drugs. Whether this increased exposure... 

The dinuclear dialkyldithiocarbamate precursor [Co2(dtc)5]+ reacted with diamine mustards N,N- and /V,/V -bis(2-chloroethyl)ethylenediamine (bee, dee) and their non-chlorinated analogs yield [Co(dtc)2(diamine)]+.1049 The bee and dee compounds were prepared and tested as potential hypoxia-selective cytotoxins, but did not prove of value as potential bioreductive anticancer drugs, partly due to their redox instability. 

There are numerous platinum(IV) complexes with nitrogen donors, most of which have been prepared as potential anticancer drugs or in the study of the reactions of such drugs. These compounds are described below in Section 6.5.6.5. 

A possible source for chemotherapeutic agents is the medicinal flora of the Asia-Pacific region. The purpose of this chapter is to provide a fundamental approach to understanding the potential of the medicinal flora of this region as a source of new anticancer drugs. 

As described above, the most common hydrophilic polymer combined with aliphatic polyesters to prepare polymer micelles is PEG. Although there have been many reports on the polymer micelles of PEG-b-aliphatic polyesters, only few recent examples are introduced in this review. Shin et al. reported the therapeutic potential of PEG-b-PLA micelles entrapping multiple anticancer drugs of poor solubility in... 

Pt(TV) Prodrugs. Platinum(IV) complexes have been widely studied as potential prodrugs that avoid the limitations of the cisplatin class of anticancer drugs. Indeed, the Pt(IV) compound satraplatin [Pt(cha)Cl2(OAc)2(NH3)] (cha, cyclohexylamine) is currently in clinical trials for treatment of hormone-refractory prostate cancer (Fig. 1) (22). Satraplatin is the first orally bioavailable platinum derivative under active clinical investigation and is particularly attractive because of the convenience of administration, milder toxicity profile, and lack of cross-resistance with cisplatin. These results are promising and support the idea that platinum(IV) complexes offer the opportunity to overcome some of the problems associated with cisplatin and its analogs. 

As the involvement of free radicals in both the initiation and promotion stages of cancer has been demonstrated (see above), it is reasonable to suggest that antioxidants may be applied for cancer treatment and prevention. Therefore, already for a long time, the effects of many antioxidants and antioxidant enzymes on cancer development have been studied under in vitro and in vivo conditions. Naturally from the beginning, much attention has been drawn to the study of possible SOD effects. Unfortunately, natural SOD has a short circulation lifetime and unable to penetrate into cells. Therefore, various SOD mimics were studied as potential anticancer drugs. 

Combretastatins are a class of compounds originally derived from the African Willow tree (Combretum caffrum) and are powerful reversible inhibitors of tubulin polymerization. This class of molecules has been shown to bind to the colchicine binding site of tubulin, by the same mode of action as mentioned above (Sect. 1.2). Combretastatins consist of a ris-slilbcnc core structure. To date, there have been several compounds that have shown promise as potential anticancer drugs. However, development of these compounds as anticancer agents is limited by issues of chemical stability, bioavailibilty, toxicity, and solubility. 

Since the discovery of the anticancer potential of Taxol , a complex compound isolated from the bark extract of the Pacific yew tree, more than 20 years ago, there has been an increasing demand for the clinical application of this compound. First, the promising results of the 1991 clinical trials in breast cancer patients were announced, and soon after Bristol-Myers-Squibb trade-marked the name Taxol and used it as an anticancer drug. At that point, the only source of the drug was the bark of the endangered yew tree. Fortunately, it was soon discovered that a precursor of Taxol could be obtained from an extract of the tree needles instead of the bark. 

The overexpression of GSTs in some cancer cells, particularly of GST Pl-1, offers an opportunity to detect and treat some cancer types (e.g., ovarian cancer). Recent developments in the design of small molecules that either inhibit the catalytic activity of GST Pl-1 or use GST Pl-1 catalytic site to release the actual anticancer agent, have shown promising results in preclinical studies, with the graduation of 66 and 96 as potential anticancer drug candidates currently undergoing clinical trials. 

---