Structure-based design and evaluation of synthetic porphyrin derivatives as G-quadruplex stabilizing anticancer agents.

OBJECTIVE: G-quadruplex structures formed in telomeres and proto-oncogene represent a potentially useful target for anticancer drugs. Stabilization of this arrangement may inhibit the further action of different enzymes involved in cancer cell immortalization. In present work structure based drug design and synthesis was carried out on series of meso-substituted porphyrin analogues. The interaction of porphyrin derivatives with G-quadruplex DNA has been explored by virtual screening procedure. Some of the potential binding agents were then synthesized and evaluated in-vitro by MTT and PCR stop assay. The study indicates that these compounds had strong G-Quadruplex binding affinity with very good inhibitory activity in MCF-7 and A549 cell lines.

Simple HPLC method for simultaneous estimation of fluconazole and tinidazole in combined dose tablet.

A rapid and sensitive reversed-phase high-performance liquid chromatographic method is developed for simultaneous estimation of fluconazole, an orally active triazole anti-fungal agent, and tinidazole, which belongs to the group of 5-nitroimidazoles in combined dose tablet. Chromatographic separation was on an ODS Hypersil C(18) column using 0.05 M potassium dihydrogen phosphate buffer (pH 3.25, adjusted with orthophosphoric acid) and acetonitrile (82:18, v/v) as the mobile phase at a flow rate of 1.5 mL/min with detection at 210 nm. The asymmetry factors are 1.36 +/- 0.04 for fluconazole and 1.26 +/- 0.07 for tinidazole with a total run time of less than 7 min. The calibration curves were linear in the range 6-14 microg/mL for fluconazole and 80-190 microg/mL for tinidazole. The method was validated with respect to linearity, precision, accuracy, and specificity. The mean recovery for fluconazole and tinidazole is 99.65 +/- 0.84 and 99.34 +/- 0.70, respectively. The utility of the procedure is verified by its application to the market formulation that was subjected to various stressed conditions. Two potential degradation products of tinidazole on exposure to alkaline stressed condition are well-resolved. The method separated the two target drugs and degradation products well. No chromatographic interference is observed.