Synthesis and antifungal activity of a novel series of alkyldimethylamine cyanoboranes and their derivatives.
A series of new amine cyanoborane derivatives were synthesized and exhibited antifungal activity. A long alkyl chain attached to the nitrogen of the amine cyanoboranes and carboxyboranes enhances antifungal activity. An enhanced activity was also obtained upon the halogenation of the amine cyanoboranes as well as in the presence of C=C double bond at the end of the N-alkyl group. The lead compounds were dimethylundecylamine cyanoborane (C11H23N(CH3)2BH2CN), 9, and its dibromo derivative dimethylundecylamine dibromocyanoborane (C11H23N(CH3)2BBr2CN), 11. The MIC values for the lead compounds against the most important human pathogenic fungi ranged from 16.25 to 32.5 micromol/L and from 10.05 to 79 micromol/L, respectively. Both compounds were found to be relatively safe in intravenous injections to mice, (MTD = 121.9 and 73.1 micromol/kg, respectively) and active against strains that are resistant to fluconazole (a conventional antifungal medicine). These data indicate their potential to become antifungal agents.
Takrouri
Khuloud
K
Department of Natural Products and Medicinal Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Oren
Gal
G
Polacheck
Itzhack
I
Sionov
Edward
E
Shalom
Eli
E
Katzhendler
Jehoshua
J
Srebnik
Morris
M
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001880:Boranes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001880:Boranes; D009570:Nitriles; D015725:Fluconazole