Cytotoxic and trypanocidal activities of cinchona alkaloid derivatives. (1st July 2018)

• Record Type: Journal Article
• Authors: Kacprzak, Karol; Ruszkowski, Piotr; Valentini, Luisa; Huczyński, Adam; Steverding, Dietmar
• Is Part Of: Chemical biology & drug design. Volume 92:Number 4(2018)
• Page Start: 1778
• Page End: 1787
• Publication Date: 2018-07-01
• Subjects: cinchona alkaloids -- cytotoxicity -- human cancer cells -- Trypanosoma brucei -- trypanotoxicity; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13346
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : A series of 27 cinchona alkaloid derivatives (1f–w, 2a–e and3a–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 and3d ) were identified with promising cytotoxic activity with 50% growth inhibition (GI50 ) values below 10 μM. Two (2e and3d ) of the four compounds also exhibited potent anti‐trypanosomal activity with GI50 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 compounds1u, 1w, 2e and3d 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. Abstract : A series of cinchona alkaloid derivatives were screened as anti‐cancer and anti‐trypanosomal agents. Derivative2e ( epi ‐ N ‐quinidyl‐ N '‐bis(3, 5‐trifluoromethyl)phenylthiourea) was identified as the most promising compound in terms of anti‐proliferating activity and selectivity for both cancer cells and trypanosomes. The results show that cinchona alkaloid derivatives could be a source of lead candidates for anti‐cancer and anti‐trypanosome drug development.