One-pot synthesis of some new regioselective 4β-pyrazolepodophyllotoxins as DNA topoisomerase-II targeting anticancer agents

The simple, efficient and recyclable Pd nanoparticles catalyzed one-pot synthesis of new library of regioselective 4β-aryl pyrazole-epipodophyllotoxin derivatives (6a-o) in environmentally benign aqueous PEG-400 media via tandem Acyl-Sonogashira coupling followed by intramolecular cyclization using TBAB as PTC was described herein. Further, these compounds were explored for their in vitro anticancer activities against five different human cancer cell lines including Colo-205 (Colon cancer), MCF-7 (breast cancer), A549 (lung cancer), PC3 (prostate cancer) and A2780 (ovarian cancer) by using MTT assay and results were compared with the standard etoposide. The results revealed that most of the synthesized compounds in micromolar concentrations were displayed more potent activity. Among all, the compounds 6b, 6f, and 6h were possessed most promising anticancer activities against four cell lines and specifically the compounds 6c and 6k displayed superior anticancer activity against entire cell lines than the standard. In addition, the in silico studies of five potent compounds 6b, 6c, 6f, 6 h and 6k were carried out to identify the interactions against DNA topoisomerase-II and found that the energy calculations were in good agreement with the obtained IC50 values.