One-Pot Synthesis of Pyrazole-Conjugated Indole Derivatives and Evaluation of Their Anticancer Activity

A series of 4-indolyl-substuted 1H-pyrazolo[3,4-b]quinolin-5(4H)-ones were synthesized by reacting 3-methyl-1-phenyl-1H-pyrazol-5-amine, 5,5-dimethylcyclohexane-1,3-dione, and indole aldehydes at 70-75 & DEG;C for 90-120 min in ethanol in the presence of l-proline as a catalyst in a green reaction medium. The synthesized compounds showed good to moderate activity against MCF-7 and DU-145 human cancer cell lines, and 4-(5-methoxy-1-methyl-1H-indol-2-yl)- and 4-(1-ethyl-5-methoxy-1H-indol-2-yl)-3,7,7-trimethyl-1-phenyl-6,7,8,9-tetrahydro-1H-pyrazolo[3,4-b]quinolin-5(4H)-ones proved the most active among the test compounds against both the test cell lines, with the IC50 values of 8.1 & PLUSMN; 0.15 and 9.9 & PLUSMN; 0.28 & mu;M (MCF-7) and 9.9 & PLUSMN; 0.28 and 11.3 & PLUSMN; 0.25 & mu;M (DU-145), respectively. The molecular modeling study revealed key interactions of these two products with Ser535 and His539 amino acid residues in the active site of B-Raf kinase.