2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro.

Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.

How to modify 7-azaindole to form cytotoxic Pt(II) complexes: highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole.

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.