Design and Synthesis of Pyridyl and 2-Hydroxyphenyl Chalcones with Antitubercular Activity.

A focussed library of pyridyl and 2-hydroxyphenyl chalcones were synthesized and tested for growth inhibitory activity against H37Rv, and normal and cancer breast cell lines. Pyridyl chalcones bearing lipophilic A-ring, e.g., dichloro-phenyl-(), pyrene-1-yl ()- and biphenyl-4-yl () moieties were found to be the most potent of the series inhibiting the growth of H37Rv with IC values ranging from 8.9-28 µM. Aryl chalcones containing a 3-methoxyphenyl A-ring and either -Br-phenyl () or -Cl-phenyl () B-rings showed an IC value of 28 µM. Aryl-chalcones were generally less toxic to HepG2 cells compared to pyridyl-chalcones. Dose-dependent antiproliferative activity against MDA468 cells was observed for trimethoxy-phenyl () and anthracene-9-yl () pyridyl-chalcones with IC values of 0.7 and 0.3 µM, respectively. Docking studies revealed that chalone was predicted to bind to the protein tyrosine phosphatases B (PtpB) with higher affinity compared to a previously reported PtpB inhibitor.