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Structure-based design and evaluation of synthetic porphyrin derivatives as G-quadruplex stabilizing anticancer agents.
Journal of Experimental Therapeutics & Oncology 2017 November
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.
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