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Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

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Abstract

We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal) of six quinoline-chalcone and five quinoline-chromone hybrids. The synthesized compounds were evaluated against amastigotes forms of Leishmania (V) panamensis, which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi, which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds 8–12, 20, 23 and 24 showed activity against Leishmania (V) panamensis, while compounds 9, 10, 12, 20 and 23 had activity against Trypanosoma cruzi with EC50 values lower than 18 mg mL−1. 20 was the most active compound for both Leishmania (V) panamensis and Trypanosoma cruzi with EC50 of 6.11 ± 0.26 μg mL−1 (16.91 μM) and 4.09 ± 0.24 (11.32 μM), respectively. All hybrids compounds showed better activity than the anti-leishmanial drug meglumine antimoniate. Compounds 20 and 23 showed higher activity than benznidazole, the current anti-trypanosomal drug. Although these compounds showed toxicity for mammalian U-937 cells,they still have the potential to be considered as candidates to antileishmanial or trypanocydal drug development.

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Acknowledgements

The authors thank Universidad de Antioquia (grant CODI IN656CE and CIDEPRO) for financial support.

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Authors and Affiliations

  1. Chemistry of Colombian Plants, Institute of Chemistry, Exact and Natural Sciences School, Universidad de Antioquia-UdeA, Calle 70 No. 52-21, A.A 1226, Medellín, Colombia

    Juan C. Coa, Elisa García & Wilson I. Cardona

  2. Department of Inorganic and Organic Chemistry, Jaume I University, E-12071, Castellón, Spain

    Miguel Carda & Raúl Agut

  3. PECET-Medical Research Institute, School of Medicine, Universidad de Antioquia-UdeA, Calle 70 No. 52-21, A.A 1226, Medellín, Colombia

    Iván D. Vélez, July A. Muñoz, Lina M. Yepes & Sara M. Robledo

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  1. Juan C. Coa
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  2. Elisa García
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  3. Miguel Carda
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  4. Raúl Agut
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  5. Iván D. Vélez
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  7. Lina M. Yepes
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  8. Sara M. Robledo
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  9. Wilson I. Cardona
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Correspondence to Sara M. Robledo or Wilson I. Cardona.

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Coa, J.C., García, E., Carda, M. et al. Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids. Med Chem Res 26, 1405–1414 (2017). https://doi.org/10.1007/s00044-017-1846-5

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  • DOI: https://doi.org/10.1007/s00044-017-1846-5

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