In this work, 21 dihydroartemisinin derivatives were synthesized, their chemical structures were characterized by 1H NMR, 13H NMR and high-resolution MS techniques, and anti-Toxoplasma gondii activity in vitro was evaluated using thiazole blue (MTT) assay. The selectivity index of compound (3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trime-thyldeca-hydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl 4-oxo-4-(pyridin-4-ylamino)butanoate (E2) was 2.24, which showed the strongest anti-T. gondii activity. In addition, the results of molecular docking studies show that E2 can be a better inhibitor of T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Therefore, compound E2 has good potential as a drug for T. gondii treatment, and further research is needed to clarify its mechanism of action.
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J. Xiao and R. H. Yolken, Acta Physiol. (Oxford), 213, 828 – 845 (2015).
A. Lass, H. Pietkiewicz, B. Szostakowska, et al., Eur. J. Clin. Microbiol. Infect. Dis., 31, 1101 – 1108 (2012).
J. G. Montoya and O. Liesenfeld, Lancet, 363, 1965 – 1976 (2004).
W. K. Chew, I. Segarra, S. Ambu, et al., Antimicrob. Agents Chemother., 56, 1762 – 1768 (2012).
E. Schoondermark-van de Ven, W. Melchers, W. Camps, et al., Antimicrob. Agents Chemother., 38, 1930 – 1936 (1994).
T. Rodrigues, D. Reker, P. Schneider, et al., Nat. Chem., 8, 531 – 541 (2016).
T. Efferth, H. Dunstan, A. Sauerbrey, et al., Int. J. Oncol., 18, 767 – 773 (2001).
C. M. Peng and H. Ousseini, Chin. Trop. Med., 9, 1462 – 1463 (2009).
X. X. Chen, J. Guang Xi Univ. Chin. Med., 15, 72 – 74 (2012).
X. Liu, J. Lu, Y. Liao, et al., Biomed. Pharmacother., 117, 109070 (2019).
T. Frohlich, F. Hahn, L. Belmudes, et al., Chem., 24, 8103 – 8113 (2018).
A. Flobinus, N. Taudon, M. Desbordes, et al., J. Antimicrob. Chemother., 69, 34 – 40 (2014).
V. Amato Neto, L. M. Braz, R. Campos, et al., Rev. Soc. Bras. Med. Trop., 24, 141 – 143 (1991).
C. P. Yang, H. J. Wan, Int. J. Med. Parasit. Dis., 33(3), 160 – 162 (2006).
H. Deng, X. Huang, C. M. Jin, et al., Bioorg. Chem., 94, 103467 (2020).
H. Y. Guo, C. M. Jin, H. M. Zhang, et al., J. Agric. Food Chem., 67, 9630 – 9642 (2019).
H. B. Zhang, Q. K. Shen, H. Wang, et al., Eur. J. Med. Chem., 158, 414 – 427 (2018).
C. M. Jin, K. Kaewintajuk, J. H. Jiang, et al., Exp. Parasitol., 121, 132 – 136 (2009).
J. H. Jiang, C. M. Jin, Y. C. Kim, et al., Bio. Pharmaceut. Bull., 12, 2273 – 2276 (2008).
R. K. Haynes, H. W. Chan, M. K. Cheung, et al., Eur. J. Org. Chem., 2002, 113 – 132 (2002).
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The authors declare that they have no conflicts of interest.
Funding
This work was supported by the National Natural Science Foundation of China (No.81960626, 82060628) and Doctoral Research Startup Fundation of Yanbian University (No. 602020087). Thanks for the language editing service provided by the Cactus Communications Co., Ltd. (Shanghai) for the manuscript
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Deng, H., Chen, ZA., Quan, YS. et al. Synthesis, Evaluation of Anti-Toxoplasma gondii Activity in vitro and Molecular Docking of Dihydroartemisinin Derivatives. Pharm Chem J 55, 1006–1014 (2022). https://doi.org/10.1007/s11094-021-02529-3
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DOI: https://doi.org/10.1007/s11094-021-02529-3