Novel potent metallocenes against liver stage malaria

Joana Matos; Filipa P. Da Cruz; Élia Cabrita; Jiri Gut; Fátima Nogueira; Virgílio E. Do Rosário; Rui Moreira; Philip J. Rosenthal; Miguel Prudêncio; Paula Gomes

doi:10.1128/AAC.05345-11

Novel potent metallocenes against liver stage malaria

Joana Matos, Filipa P. Da Cruz, Élia Cabrita, Jiri Gut, Fátima Nogueira, Virgílio E. Do Rosário, Rui Moreira, Philip J. Rosenthal, Miguel Prudêncio, Paula Gomes

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ∼45-fold-higher level activity against liver stage parasitemia than that of primaquine.

Original language	English
Pages (from-to)	1564-1570
Number of pages	7
Journal	Antimicrobial Agents and Chemotherapy
Volume	56
Issue number	3
DOIs	https://doi.org/10.1128/AAC.05345-11
Publication status	Published - Mar 2012

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abstract = "Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ∼45-fold-higher level activity against liver stage parasitemia than that of primaquine.",

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T1 - Novel potent metallocenes against liver stage malaria

AU - Matos, Joana

AU - Da Cruz, Filipa P.

AU - Cabrita, Élia

AU - Gut, Jiri

AU - Nogueira, Fátima

AU - Do Rosário, Virgílio E.

AU - Moreira, Rui

AU - Rosenthal, Philip J.

AU - Prudêncio, Miguel

AU - Gomes, Paula

PY - 2012/3

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AB - Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ∼45-fold-higher level activity against liver stage parasitemia than that of primaquine.

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Novel potent metallocenes against liver stage malaria

Abstract

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