2. Academic Validation
  3. Antitubercular activity of quinolizidinyl/pyrrolizidinylalkyliminophenazines

Antitubercular activity of quinolizidinyl/pyrrolizidinylalkyliminophenazines

  • Bioorg Med Chem. 2014 Dec 15;22(24):6837-45. doi: 10.1016/j.bmc.2014.10.035.
Michele Tonelli 1,  Federica Novelli 2,  Bruno Tasso 2,  Anna Sparatore 3,  Vito Boido 2,  Fabio Sparatore 2,  Sara Cannas 4,  Paola Molicotti 4,  Stefania Zanetti 5,  Silvia Parapini 6,  Roberta Loddo 7
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy. Electronic address: michele.tonelli@unige.it.
  • 2 Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
  • 3 Dipartimento di Scienze Farmaceutiche, Università di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
  • 4 Dipartimento di Scienze Biomediche, Università di Sassari, Viale San Pietro, 07100 Sassari, Italy.
  • 5 Dipartimento di Scienze Biomediche, Università di Sassari, Viale San Pietro, 07100 Sassari, Italy. Electronic address: zanettis@uniss.it.
  • 6 Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Via C. Pascal 36, 20133 Milano, Italy.
  • 7 Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
PMID: 25464882 DOI: 10.1016/j.bmc.2014.10.035
Abstract

Novel riminophenazine derivatives, characterized by the presence of the basic and cumbersome quinolizidinylalkyl and pyrrolizidinylethyl moieties, have been synthesized and tested (Rema test) against Mycobacterium tuberculosis H37Rv and H37Ra, and six clinical isolates of Mycobacterium avium and Mycobacterium tuberculosis. Most compounds exhibited potent activity against the tested strains, resulting more active than clofazimine, isoniazid and ethambutol. The best compounds (4, 5, 12 and 13) exhibited a MIC in the range 0.82-0.86μM against all strains of Mycobacterium tuberculosis and, with the exception of 4 a MIC around 3.3μM versus M. avium. The corresponding values for clofazimine (CFM) were 1.06 and 4.23μM, respectively. Cytotoxicity was evaluated against three cell lines and compound 4 displayed a selectivity index (SI) versus the human cell line MT-4 comparable with that of CFM (SI=5.23 vs 6.4). Toxicity against mammalian Vero 76 cell line was quite lower with SI=79.

Keywords

Antitubercular activity; Clinical isolates of Mycobacterium tuberculosis; Mycobacterium avium; Mycobacterium tuberculosis; Quinolizidinyl- and pyrrolizidinyl-alkyliminophenazine derivatives.

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