Clofazimine analogs with antileishmanial and antiplasmodial activity

  • Bioorg Med Chem. 2015 Jan 1;23(1):55-65. doi: 10.1016/j.bmc.2014.11.028.
Anna Barteselli  1 ,  Manolo Casagrande  1 ,  Nicoletta Basilico  2 ,  Silvia Parapini  3 ,  Chiara M Rusconi  1 ,  Michele Tonelli  4 ,  Vito Boido  4 ,  Donatella Taramelli  3 ,  Fabio Sparatore  4 ,  Anna Sparatore  5
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
  • 2. Dipartimento di Scienze Biomediche Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Via C. Pascal 36, 20133 Milano, Italy.
  • 3. Dipartimento di Scienze Farmacologiche e Biomolecolari-DiSFeb, Università degli Studi di Milano, via C. Pascal 36, 20133 Milano, Italy.
  • 4. Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
  • 5. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy. Electronic address: [email protected].
PMID: 25497962 DOI: 10.1016/j.bmc.2014.11.028
Abstract

A set of novel riminophenazine derivatives has been synthesized and evaluated for in vitro activity against chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains of Plasmodium falciparum and against different species of Leishmania promastigotes. Most of the new compounds inhibited the growth of Leishmania promastigotes as well as CQ-S and CQ-R strains of P. falciparum with IC50 in submicromolar range, resulting in the best cases 1-2 orders of magnitude more potent than the parent compound clofazimine.

Keywords
Antileishmanial activity; Antiplasmodial activity; Clofazimine; Clofazimine analogs; Pyrrolizidinyl-alkyliminophenazine derivatives; Quinolizidinyl-alkyliminophenazine derivatives.