Modification of Biphenolic Anti-Bacterial to Achieve Broad-Spectrum Activity.
Modification of Biphenolic Anti-Bacterial to Achieve Broad-Spectrum Activity.
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DOI：
10.1002/cmdc.202100783
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发表时间：
2022-05-04
期刊：
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
革兰氏阳性菌耐甲氧西林金黄色葡萄球菌（MRSA）和革兰氏阴性菌鲍曼不动杆菌是导致全球数百万医院感染的病原体。由于细菌对抗生素产生耐药性的威胁，科学家们一直在寻找新的化合物来治疗感染性疾病。对口腔细菌最有效的和厚朴酚类似物对MRSA具有相似的生物活性。然而，所有化合物均被证明对A.鲍曼不动杆菌。不能抑制A.鲍曼不动杆菌是由于难以穿透脂多糖包被的外膜，这使得抗生素难以进入革兰氏阴性细菌。C2支架从抑制革兰氏阳性菌优化为抑制危险的革兰氏阴性病原体A的广谱抗菌化合物。鲍曼不动杆菌。革兰氏阳性菌（包括MRSA）的强效双酚抑制剂已被置换为广谱类似物。通过O-取代或通过取代叔丁基引入含胺基团导致比莫匹罗星更有效且具有更高治疗指数的化合物，莫匹罗星是针对革兰氏阴性A的最有效的抗微生物剂之一。研究所和/或研究员
The gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria, Acinetobacter baumannii, are pathogens responsible for millions of nosocomial infections worldwide. Due to the threat of bacteria evolving resistance to antibiotics, scientists are constantly looking for new classes of compounds to treat infectious diseases. The biphenolic analogs of honokiol that were most potent against oral bacteria had similar bioactivity against MRSA. However, all the compounds proved ineffective against A. baumannii. The inability to inhibit A. baumannii is due to the difficult-to-penetrate lipopolysaccharide-coated outer membrane that makes it challenging for antibiotics to enter gram-negative bacteria. The C2 scaffold was optimized from the inhibition of gram-positive bacteria to broad-spectrum antibacterial compounds that inhibit the dangerous gram-negative pathogen A. baumannii. A potent biphenolic inhibitor of gram-positive bacteria including MRSA has been permuted to a broad spectrum analog. Incorporation of amine containing groups by O-substitution or by replacement of tert-butyl groups led to a compound both more potent and with a higher therapeutic index than mupirocin, one of the most effective antimicrobial agents against gram negative A. baumannii.Institute and/or researcher
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影响因子：
64.8
作者：
Richter MF;Drown BS;Riley AP;Garcia A;Shirai T;Svec RL;Hergenrother PJ
通讯作者：
Hergenrother PJ
影响因子：
4.9
作者：
SUTHERLAND, R;BOON, RJ;WHITE, AR
通讯作者：
WHITE, AR
影响因子：
4.9
作者：
HAMMES, WP;NEUHAUS, FC
通讯作者：
NEUHAUS, FC
影响因子：
5
作者：
Carre, N.;Sillam, F.;Coignard, B.
通讯作者：
Coignard, B.
影响因子：
9
作者：
Halasi M;Hitchinson B;Shah BN;Váraljai R;Khan I;Benevolenskaya EV;Gaponenko V;Arbiser JL;Gartel AL
通讯作者：
Gartel AL