Antiparasitic hybrids of Cinchona alkaloids and bile acids
(2013) European Journal of Medicinal Chemistry — Vol. 66, p. 355-363 (2013)
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- A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC₅₀ values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC₅₀ ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC₅₀ values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7.
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Leverrier, A., Bero, J., Frédérich, M., Leclercq, J., & Palermo, J. (2013). Antiparasitic hybrids of Cinchona alkaloids and bile acids. European Journal of Medicinal Chemistry, 66, 355-363. https://doi.org/10.1016/j.ejmech.2013.06.004 (Original work published 2013)