Synthesis and antiplasmodial activity of bicyclic dioxanes as simplified dihydroplakortin analogues

Sandra Gemma; Sanil Kunjir; Salvatore Sanna Coccone; Margherita Brindisi; Vittoria Moretti; Simone Brogi; Ettore Novellino; Nicoletta Basilico; Silvia Parapini; Donatella Taramelli; Giuseppe Campiani; Stefania Butini

doi:10.1021/jm200686d

Synthesis and antiplasmodial activity of bicyclic dioxanes as simplified dihydroplakortin analogues

J Med Chem. 2011 Aug 25;54(16):5949-53. doi: 10.1021/jm200686d. Epub 2011 Jul 29.

Authors

Sandra Gemma¹, Sanil Kunjir, Salvatore Sanna Coccone, Margherita Brindisi, Vittoria Moretti, Simone Brogi, Ettore Novellino, Nicoletta Basilico, Silvia Parapini, Donatella Taramelli, Giuseppe Campiani, Stefania Butini

Affiliation

¹ European Research Centre for Drug Discovery and Development (NatSynDrugs), 53100 Siena, Italy.

PMID: 21761935
DOI: 10.1021/jm200686d

Abstract

Here we report the synthesis and evaluation of antiplasmodial activity of a novel series of bicyclic peroxides inspired by the marine natural compound dihydroplakortin. We developed a synthetic strategy leading to the dihydroplakortin-related peroxides in only a few steps. The in vitro antiplasmodial potency of the peroxides was similar to, or greater than, that of the reference natural compound, and structure-activity relationship studies revealed several key structural requirements for activity and potency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology*
Dioxanes / chemical synthesis*
Dioxanes / chemistry
Dioxanes / pharmacology*
Dose-Response Relationship, Drug
Models, Chemical
Models, Molecular
Molecular Conformation
Molecular Structure
Peroxides / chemical synthesis
Peroxides / chemistry
Peroxides / pharmacology
Plasmodium falciparum / drug effects*
Plasmodium falciparum / growth & development
Structure-Activity Relationship

Substances

Antimalarials
Dioxanes
Peroxides