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Cytotoxic and trypanocidal activities of cinchona alkaloid derivatives
Author(s) -
Kacprzak Karol,
Ruszkowski Piotr,
Valentini Luisa,
Huczyński Adam,
Steverding Dietmar
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13346
Subject(s) - trypanosoma brucei , hela , cytotoxic t cell , alkaloid , cinchona , chemistry , cancer cell , growth inhibition , apoptosis , cytotoxicity , cell culture , stereochemistry , biochemistry , pharmacology , cancer , biology , cell , in vitro , enantioselective synthesis , genetics , gene , catalysis
A series of 27 cinchona alkaloid derivatives ( 1f–w , 2a–e and 3a–d ) were investigated for their cytotoxic and trypanocidal activities using seven different cancer cell lines ( KB , HeLa, MCF ‐7, A‐549, Hep‐G2, U‐87 and HL ‐60), two normal cell lines ( HDF and CHO ) and bloodstream forms of Trypanosoma brucei brucei , respectively. Four compounds ( 1u , 1w , 2e and 3d ) were identified with promising cytotoxic activity with 50% growth inhibition ( GI 50 ) values below 10 μM. Two ( 2e and 3d ) of the four compounds also exhibited potent anti‐trypanosomal activity with GI 50 values of 0.3–0.4 μM. All four active compounds represented derivatives modified at their C‐9 hydroxy group. With respect to anti‐proliferative activity and selectivity, 2e ( epi ‐ N ‐quinidyl‐ N ′‐bis(3,5‐trifluoromethyl)phenylthiourea) proved to be the most promising derivative for both cancer cells and bloodstream forms of T. b. brucei . The cytotoxic activity of compounds 1u , 1w , 2e and 3d was attributed to their ability to induce apoptosis in cancer cells. The results demonstrate the potential of cinchona alkaloid derivatives as novel anti‐cancer and anti‐trypanosome drug candidates.