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

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Abstract

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°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 ± 0.15 and 9.9 ± 0.28 µM (MCF-7) and 9.9 ± 0.28 and 11.3 ± 0.25 µM (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.

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ACKNOWLEDGMENTS

The authors are very grateful to the authorities of DST–PURSE, Department of Chemistry, Osmania University, Hyderabad, Telangana, and the CSIR for providing funds and fellowship support.

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Authors and Affiliations

  1. Osmania University, Department of Chemistry, 500007, Hyderabad, India

    Kurapati Ravi, Bala Narsimha Dhoddi, Jalapathi Pochampally & Raghavender Matta

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  1. Kurapati Ravi
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  2. Bala Narsimha Dhoddi
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  3. Jalapathi Pochampally
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Correspondence to Jalapathi Pochampally.

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Ravi, K., Dhoddi, B.N., Pochampally, J. et al. One-Pot Synthesis of Pyrazole-Conjugated Indole Derivatives and Evaluation of Their Anticancer Activity. Russ J Org Chem 59, 924–931 (2023). https://doi.org/10.1134/S1070428023050238

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