Synthesis and molecular-cellular mechanistic study of pyridine derivative of dacarbazine

Dacarbazine is an antitumor prodrug which is used for the treatment of malignant metastatic melanoma and Hodgkin's disease. It requires initial activation in liver through an N-demethylationreaction. The active metabolite prevents the progress of disease via alkylation of guanine bases in DNA strands. In order to investigate the importance of imidazole ring and its dynamictautomerization in anticancer activity of dacarbazine, a pyridine analog of this drug was synthesized and the cytotoxic activity and cellular-molecular mechanisms of action for this compound were compared with those of dacarbazine. EC50 values for dacarbazine and the pyridine analog were found to be 56 micro M and 33 micro M respectively. Both dacarbazine and the pyridine analog resulted in formation of reactive oxygen species [ROS] upon their addition to the isolated rat hepatocytes. They also decreased the mitochondrial membrane potential and caused lysosomal membrane rupture. Cytotoxicity was prevented by ROS scavengers and antioxidants. Cytotoxicity was also prevented by CYP[450] inhibitors, lysosomalinactivators and MPT [Mitochondrial Permeability Transition Pore] blockers

convenient simple method for synthesis of meta-iodobenzylguanidine [MIBG]

Radioiodinated meta-iodobenzylguanidine [MIBG] is one of the important radiopharmaceuticals in Nuclear Medicine. [123/131] MIBG is used for imaging of Adrenal medulla, studying heart sympathetic nerves, treatment ofpheochromacytoma and neuroblastoma. For clinical application, radioiodinated MIBG is prepared through isotopic exchange method, which includes replacement of radioactive iodine in a nucleophilic substitution reaction with cold iodine [127I]. The unlabelled MIBG hemisulfate is synthesized by the procedure described by Wieland et al. [1980]. The availability of a more practical and cost-effective procedure for MIBG preparation encouraged us to study the MIBG synthesis methods. In this study the v preparation of MIBG through different methods were evaluated and a new method, which is one step, simple and cost-effective is introduced. The method has ability to be scaled up for production of unlabelled MIBG

Synthesis and antimycobacterial activity of symmetric thiocarbohydrazone derivatives against Mycobacterium bovis BCG

In this work, we reported the synthesis and evaluation of antimycobacterial and antifungal activity of a series of thiocarbohydrazone derivatives which are thiacetazone congeners. The target compounds were synthesized in superior yields by reacting thiocarbohydrazide with different aromatic aldehydes and methyl ketones. Compounds 8, 19 and 25 were found to be the most potent derivatives, exhibiting acceptable activity against Mycobacterium bovis BCG compared to thiacetazone and ethambutol as reference substances. Compounds 8, 15 and 25 exhibited the highest activity against Candida albicans. The most active compounds had a completely different aromatic ring system with various electronic, steric and lipophilic natures. This is understandable in light of the fact that carbohydrazone derivatives must undergo a metabolic activation step before exerting their anti-TB activity and different SAR rules govern each one of these two processes