title: How to modify 7-azaindole to form cytotoxic Pt(II) complexes: highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole.
abstract: The platinum(II) dichlorido and oxalato complexes of the general formula cis-[PtCl(2)(nHaza)(2)] (1-3) [Pt(ox)(nHaza)(2)] (4-6) involving 7-azaindole halogeno-derivatives (nHaza) were prepared and thoroughly characterized. A single-crystal X-ray analysis of cis-[PtCl(2)(3ClHaza)(2)]·DMF (1·DMF; 3ClHaza symbolizes 3-chloro-7-azaindole) revealed a distorted square-planar arrangement with both the 3ClHaza molecules coordinated through their N7 atoms in a cis fashion. In vitro cytotoxicity of the complexes was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay against the HOS (osteosarcoma), MCF7 (breast adenocarcinoma) and LNCaP (prostate adenocarcinoma) human cancer cell lines. The dichlorido complexes 1-3 (IC(50)=3.8, 3.9, and 2.5 μM, respectively) showed significantly higher in vitro anticancer effect against HOS as compared with cisplatin, whose IC(50)=37.7 μM. The biological effect of cisplatin against MCF7 (IC(50)=24.5 μM) and LNCaP (IC(50)=3.8 μM) was also exceeded by 1-3 (except for 2 against LNCaP), but the difference can be classified as significant only in the case of 1 (IC(50)=3.4 μM) and 3 (IC(50)=2.0 μM) against MCF7. The molecular pharmacological studies (RNA synthesis by T7 RNA polymerase in vitro) proved that 1-3 bind to DNA in a similar manner as cisplatin, since the RNA synthesis products of 1-3 and cisplatin showed a similar sequence profile of major bands.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, CZ-77146 Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Štarha
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
authors.forename: Alexandr
authors.initials: A
authors.lastname: Popa
authors.forename: Igor
authors.initials: I
authors.lastname: Popa
authors.forename: Tereza
authors.initials: T
authors.lastname: Muchová
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis
chemical_list: C023422:7-azaindole dimer; D000970:Antineoplastic Agents; D003603:Cytotoxins; D007211:Indoles; D012334:RNA, Neoplasm; D012313:RNA; D002945:Cisplatin