L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.
A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and R2 being in general long-chain alkyl substituents. The series shows good activity against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been measured by RP-HPLC method to give the logarithm of the experimental capacity factor (log k'), and a quantitative relationship has been determined between log k' and the theoretical partition coefficient (CLOGP); also, bond-dipole descriptors have been introduced into calculations by accounting for polar moieties present within the apolar cores of the molecules, giving a more refined calculated capacity factor (log k'calcd). Finally the latter has been related to the antimicrobial activity (MIC values). The proposed models are predictive for the best broad-spectrum antimicrobial compound within the series.
Calvani
M
M
Direzione Ricerca Sigma-Tau S.p.A., Via Pontina Km 30, 400, I-00040 Pomezia (Rome), Italy.
Critelli
L
L
Gallo
G
G
Giorgi
F
F
Gramiccioli
G
G
Santaniello
M
M
Scafetta
N
N
Tinti
M O
MO
De Angelis
F
F
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004952:Esters; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004952:Esters; D000644:Quaternary Ammonium Compounds; D002331:Carnitine