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Activities of 11‐Azaartemisinin and N ‐Sulfonyl Derivatives against Neospora caninum and Comparative Cytotoxicities
Author(s) -
Harmse Rozanne,
Wong Ho Ning,
Smit Frans J.,
Müller Joachim,
Hemphill Andrew,
N'Da David D.,
Haynes Richard K.
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700600
Subject(s) - neospora caninum , cytotoxicity , sulfonyl , neospora , cell culture , chemistry , biology , microbiology and biotechnology , in vitro , immunology , biochemistry , antibody , organic chemistry , toxoplasma gondii , alkyl , genetics
Neosporosis caused by the apicomplexan parasite Neospora caninum is an economically important disease that induces abortion in dairy and beef cattle. There are no vaccines or drugs available on the market for control or treatment of the disease in bovines. The peroxide artemisinin and its derivatives used clinically for treatment of malaria are active against N. caninum and other apicomplexan parasites. We have now evaluated the activities of the readily accessible and chemically robust 11‐azaartemisinin 5 and selected N ‐sulfonyl derivatives prepared as described in the accompanying paper against N. caninum tachyzoites grown in infected human foreskin fibroblasts. Azaartemisinin elicited an IC 50 value of 150 n m , and the 2′,5′‐dichloro‐3′‐thienylsulfonyl‐11‐azaartemisinin 17 was found to be the most active, with an IC 50 value of 40 n m . Comparison with normal human fetal lung fibroblasts HFLF WI‐38 revealed relatively benign cytotoxicity. The compounds were also screened in vitro against TK‐10 (renal), UACC‐62 (melanoma) and MCF‐7 (breast) cancer cell lines; overall, in line with activities against HFLF cells, most compounds in the series were found to be inactive.