Cisplatin-derivatives anticancer activity

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. 

Recent reviews in the field of platinum anticancer drugs focus on platinum-nucleobase chemistry [7], biological processing of platinum-modified DNA [8], trans-platinum anticancer drugs [5], cisplatin and derived anticancer drugs [4,9], proteins and cisplatin [10], trans-diam-mineplatinum(II) and nucleic acids [11], and catalytic activity and DNA [12], just to mention a few. The aim of this review is to explore the chemistry in the interaction of various platinum compounds with nucleic... 

Cisplatin is a neutral square planar coordination complex with two chloride and ammonium ligands in the cis-configuration. The compounds with trans-configuration are mostly devoid of activity. Pt exists in two main oxidation states, namely Pt [Pt(II) and Pt4+ Pt(IV)]. In the latter, two of the ligands are located axially directly above and below the square plane, which results in an octahedral configuration. Although many of the Pt(IV) derivatives exhibit anticancer activity, only the Pt(II) complexes with cis-configuration have become widely applied in the clinical practice [2]. 

The platinum derivatives, cisplatin, carboplatin, and oxaliplatin are anticancer agents with remarkable usefulness in cancer treatment (see Table 124-14). Recognition of cisplatin s cytotoxic activity was... 

As mentioned in the introduction, metallocene-type complexes based on the early transition metals were evaluated as anticancer compounds shortly after the discovery of cisplatin. While the biological activity of each of the metallocene dihalides is unique, titanocene dichloride 7 has been the subject of a number of studies and even entered clinical evaluation, although evaluation was discontinued (not due to its anti-proliferative properties), principally due to formulation problems, despite showing superior activity to certain cancers than other established drugs. This class of compound continues to be modified and studied for anticancer activity, for example, the titanocene-type derivative of tamoxifen 1, described above, and other developments described below. 

Since the discovery by Rosenberg [88] that cisplatin is an effective anticancer drug, large synthesis and evaluation programs have aimed at the creation of cisplatin derivatives that show greater and more wide-spread activity against cancer but with... 

The many works related to platinum-containing anticancer drugs include a review of the binding of Cisplatin to DNA. Also of importance in this field are two communications concerning the known preference of Pt(II) to bond to N-7 of guanine and its derivatives. The affinity of platinum for particular sites is enhanced by the presence of an adjacent guanine. The active species of Cisplatin are ci5-[PtCl2(NH3)2] itself and the mono-aquo cation with which it equilibrates. 

A few synthetic approaches were reported to obtain sets of new 1,2,4-triazine derivatives. A well-known synthetic protocol was used to prepare a series of the 1,2,4-triazine derivatives 14 bearing a piperazine amide moiety. The synthetic route included the condensation of S-methyl thiosemicarba-zide 15 and benzil derivatives 16 followed by nucleophilic substitution of the methylthio group with piperazine resulting in 1,2,4-triazines 17 and further functionalization of the piperazine moiety. In vitro antitumor activity against breast cancer cells of the 1,2,4-triazines 14 was evaluated using the XTT method, BrdU method, and flow cytometric analysis. A few of the compounds demonstrated antiproliferative effect comparable with an effective anticancer drug, cisplatin (14BMC6313). 

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