Antimycobacterial activity of ionic fullerene derivatives

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Abstract

Positively charged fullerene derivatives, moderately soluble in water:DMSO 9:1, have been tested using three strains of Mycobacterium spp. Some compounds inhibit the growth of Mycobacterium tubercolosis, a human clinical isolate, particularly virulent and resistant, at doses as low as 5 μg/mL.

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Synthesis

Fulleropyrrolidines 13 were prepared according to Scheme 1.9, 12, 13 Compounds 13 are characterized by the presence of triethylene glycol monomethyl ether chains either on nitrogen and/or on carbon 2 of the pyrrolidine ring. All the compounds were dissolved in DMSO and diluted with water. Neutral derivatives 13 exhibited solubility values in water:DMSO 90:10 in the low 10−5 M range (Table 1). The same compounds were subjected to methylation using methyl iodide to obtain the three

Biological tests

Two strains of M. tuberculosis: strain H37Rv, reference strain, and strain H6/99, a recent clinical isolate, obtained from a pneumological clinic in Trieste, particularly virulent and resistant, and a strain of M. avium, strain 485, were chosen to test the salts and the most soluble fulleropyrrolidine 3.

Each compound (5 mg) was dissolved in 10 mL of DMSO (solution A). Dilutions from solution A gave solution B (50 μg/mL), and solution C (5 μg/mL), both in DMSO:H2O 1:9. Sterile Eppendorf vials

Acknowledgements

Financial contribution from MURST (cofin. ex 40%, prot. no. 9803194198_005) is gratefully acknowledged.

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