Calvani M, Critelli L, Gallo G, Giorgi F, Gramiccioli G, Santaniello M, Scafetta N, Tinti M O, De Angelis F
Direzione Ricerca Sigma-Tau S.p.A., Via Pontina Km 30, 400, I-00040 Pomezia (Rome), Italy.
J Med Chem. 1998 Jun 18;41(13):2227-33. doi: 10.1021/jm970305x.
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.
已设计出一类新型的抗菌“软”季铵型L-肉碱酯，其结构为(CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-，其中R1和R2通常为长链烷基取代基。该系列对多种细菌、酵母和真菌均表现出良好的活性。通过反相高效液相色谱法测定亲脂性，得出实验容量因子的对数(log k')，并确定了log k'与理论分配系数(CLOGP)之间的定量关系；此外，通过考虑分子非极性核心中存在的极性部分，将键偶极描述符引入计算，得出更精确的计算容量因子(log k'calcd)。最后，将后者与抗菌活性(MIC值)相关联。所提出的模型可预测该系列中最佳的广谱抗菌化合物。
