Antitubercular activity of quinolizidinyl/pyrrolizidinylalkyliminophenazines

作者：Tonelli Michele^*; Novelli Federica; Tasso Bruno; Sparatore Anna; Boido Vito; Sparatore Fabio; Cannas Sara; Molicotti Paola; Zanetti Stefania; Parapini Silvia; Loddo Roberta

来源：BIOORGANIC %26 MEDICINAL CHEMISTRY, 2014, 22(24): 6837-6845.

DOI：10.1016/j.bmc.2014.10.035

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

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. %26lt;br%26gt;The best compounds (4, 5, 12 and 13) exhibited a MIC in the range 0.82-0.86 mu M against all strains of Mycobacterium tuberculosis and, with the exception of 4 a MIC around 3.3 mu M versus M. avium. The corresponding values for clofazimine (CFM) were 1.06 and 4.23 mu M, 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.

• 出版日期2014-12-15