Further optimization of plakortin pharmacophore: Structurally simple 4-oxymethyl-1,2-dioxanes with promising antimalarial activity
Articolo
Data di Pubblicazione:
2013
Citazione:
Further optimization of plakortin pharmacophore: Structurally simple 4-oxymethyl-1,2-dioxanes with promising antimalarial activity / M. Persico, S. Parapini, G. Chianese, C. Fattorusso, M. Lombardo, L. Petrizza, A. Quintavalla, F. Rondinelli, N. Basilico, D. Taramelli, C. Trombini, E. Fattorusso, O. Taglialatela-Scafati. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 70(2013 Oct), pp. 875-886.
Abstract:
For the optimization of the plakortin pharmacophore, we recently proposed a straightforward synthesis
of 4-carbomethoxy-3-methoxy-1,2-dioxanes as potential antimalarial drug candidates. Herein we report
the chemoselective reduction of the 4-carbomethoxy group which has allowed us to prepare in good
yields twenty-four new endoperoxides carrying either the hydroxymethyl or the methoxymethyl group
on C4 in various stereochemical arrangements with respect to the alkyl groups on C3 and C6 (the
endoperoxide carbons). Some of these compounds showed promising in vitro antimalarial activities, both
against chloroquine-resistant (CQ-R) and susceptible (CQ-S) strains of Plasmodium falciparum, with IC50
values in the range of 0.5e1.0 mM. Compound 8g showed activity against the CQ-R strain comparable to
that of the structurally more demanding plakortin.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
1,2-Dioxanes Malaria ; Antimalarial drugs ; SAR ; DFT
Elenco autori:
M. Persico, S. Parapini, G. Chianese, C. Fattorusso, M. Lombardo, L. Petrizza, A. Quintavalla, F. Rondinelli, N. Basilico, D. Taramelli, C. Trombini, E. Fattorusso, O. Taglialatela-Scafati
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