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With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their antiproliferative activity against 60 different human tumor cell lines was validated by the U.S. National Cancer Institute using a two stage process. The  in vitro  anticancer evaluation revealed that compound  9  showed increased potency toward most human tumor cell lines with GI 50 MG-MID = 3.59 µM, as compared to the standard drug sorafenib (GI 50  MG-MID = 1.90 µM). At the same time, compounds  6a  and  7  were selective against the HOP-92 cell line of non-small cell lung cancer with GI 50  1.65 and 1.61 µM, respectively.

Biological Validation of Novel Polysubstituted Pyrazole Candidates with in Vitro Anticancer Activities