Synthesis of new α-Aryl-α-tetralones and α-Fluoro-α-aryl-α-tetralones, preliminary antiproliferative evaluation on drug resistant cell lines and in silico prediction of ADMETox properties.

Luana G de Souza, Eduardo J Salustiano, Kelli M da Costa, Angela T Costa, Vivian M Rumjanek, Jorge L O Domingos, Magdalena N Rennó, Paulo R R Costa

Bioorganic chemistry 2021 May

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α-aryl-α-tetralones and α-fluoro-α-aryl-α-tetralones derivatives were synthesized by palladium catalyzed α-arylation reaction of α-tetralones and α-fluoro-α-tetralones, with bromoarenes in moderate to good yields. These compounds were evaluated for their in vitro anti-proliferative effects against human breast cancer and leukemia cell lines with diverse profiles of drug resistance. The most promising compounds, 3b, 3c, 8a and 8c, were effective on both neoplastic models. 3b and 8a induced higher toxicity on multidrug resistant cells and were able to avoid efflux by ABCB1 and ABCC1 transporters. Theoretical calculations of the physicochemical descriptors to predict ADMETox properties were favorable concerning Lipinski's rule of five, results that reflected on the low effects on non-tumor cells. Therefore, these compounds showed great potential for development of pharmaceutical agents against therapy refractory cancers. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Luana G de Souza, Eduardo J Salustiano, Kelli M da Costa, Angela T Costa, Vivian M Rumjanek, Jorge L O Domingos, Magdalena N Rennó, Paulo R R Costa. Synthesis of new α-Aryl-α-tetralones and α-Fluoro-α-aryl-α-tetralones, preliminary antiproliferative evaluation on drug resistant cell lines and in silico prediction of ADMETox properties. Bioorganic chemistry. 2021 May;110:104790