Design, synthesis and biological evaluation of novel pyrazolo-oxothiazolidine derivatives as antiproliferative agents against human lung cancer cell line A549.

An efficient, one-pot multicomponent reaction of novel pyrazolo-oxothiazolidine derivatives was achieved by condensation of 1-(benzofuran-2-yl)-3-(substituted-arylprop-2-en-1-ones, thiosemicarbazide and dialkyl acetylenedicarboxylates under the optimized reaction conditions. Synthesised compounds were evaluated for their antiproliferative activity against A549 human lung cancer cell line. Among all the tested compounds, 4a (IC50 - 0.930 µg/mL), 4e (IC50 - 1.207 µg/mL), 4f (IC50 - 0.808 µg/mL), 4g (IC50 - 1.078 µg/mL), 4h (IC50 - 0.967 µg/mL) and 4j (IC50 - 2.445 µg/mL) showed promising activity compared with standard drug Sorafenib (IC50 - 3.779 µg/mL). Molecular docking studies indicated that compound 4f had the greatest affinity for catalytic site of receptors EGFR (PDB ID code: 1 M17) and VEGFR2 (PDB ID code: 4AGD, 4ASD). These novel pyrazolo-oxothiazolidine derivatives can be promising therapeutic agents for A549 human lung cancer cell line.