Structure-Activity Relationships for Antibacterial to Antifungal Conversion of Kanamycin to Amphiphilic Analogues
Structure-Activity Relationships for Antibacterial to Antifungal Conversion of Kanamycin to Amphiphilic Analogues
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DOI：
10.1021/acs.joc.5b00248
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发表时间：
2015-05-01
影响因子：
3.6
通讯作者：
Chang, Cheng-Wei Tom
中科院分区：
文献类型：
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作者：
Fosso, Marina;AlFindee, Madher N.;Chang, Cheng-Wei Tom
迫切需要新的杀真菌剂。最近有报道，在卡那霉素B的O-4“位上连接一个辛基，将这种抗菌氨基糖苷转化为一种新的抗真菌剂。为了阐明这一现象的构效关系（SAR），合成了一种先导化合物FG 03，其羟基取代卡那霉素B的3“-NH 2基团。FG 03的抗真菌活性和合成方案启发了在各种羟基上烷基化的卡那霉素B类似物库的合成。特别行政区对该文库的研究表明，对于抗真菌活性，O-4 "位是连接线性烷基链的最佳位点，卡那霉素B母体分子的3“-NH 2和6”-OH基团对于抗真菌活性不是必需的。先导化合物FG 03的发现是通过简单的化学修饰恢复临床废弃药物如卡那霉素的一个例子，也是发现新型抗菌剂的替代策略。
Novel fungicides are urgently needed. It was recently reported that the attachment of an octyl group at the O-4 '' position of kanamycin B converts this antibacterial aminoglycoside into a novel antifungal agent. To elucidate the structure-activity relationship (SAR) for this phenomenon, a lead compound FG03 with a hydroxyl group replacing the 3 ''-NH2 group of kanamycin B was synthesized. FG03's antifungal activity and Synthetic scheme inspired the synthesis of a library of kanamycin B analogues alkylated at various hydroxyl groups. SAR. studies of the library revealed that for antifungal activity the O-4 '' position is the optimal site for attaching a linear alkyl chain and that the 3 ''-NH2 and 6 ''-OH groups of the kanamycin B parent molecule are not essential for antifungal activity. The discovery of lead compound, FG03, is an example of reviving clinically obsolete drugs like kanamycin by simple chemical modification and an alternative strategy for discovering novel antimicrobials.