890017-26-2Relevant articles and documents
Rational Design of Dipicolylamine-Containing Carbazole Amphiphiles Combined with Zn2+as Potent Broad-Spectrum Antibacterial Agents with a Membrane-Disruptive Mechanism
Liu, Jiayong,Li, Hongxia,Li, Haizhou,Fang, Shanfang,Shi, Jinguo,Chen, Yongzhi,Zhong, Rongcui,Liu, Shouping,Lin, Shuimu
, p. 10429 - 10444 (2021)
Antibiotic resistance has become one of the most urgently important problems facing healthcare providers. A novel series of dipicolylamine-containing carbazole amphiphiles with strong Zn2+chelating ability were synthesized, biomimicking cationic antimicrobial peptides. Effective broad-spectrum 16 combined with 12.5 μg/mL Zn2+was identified as the most promising antimicrobial candidate. 16 combined with 12.5 μg/mL Zn2+exhibited excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria (MICs = 0.78-3.125 μg/mL), weak hemolytic activity, and low cytotoxicity. Time-kill kinetics and mechanism studies revealed 16 combined with 12.5 μg/mL Zn2+had rapid bacterial killing properties, as evidenced by disruption of the integrity of bacterial cell membranes, effectively preventing bacterial resistance development. Importantly, 16 combined with 12.5 μg/mL Zn2+showed excellentin vivoefficacy in a murine keratitis model caused byStaphylococcus aureusATCC29213 orPseudomonas aeruginosaATCC9027. Therefore, 16 combined with 12.5 μg/mL Zn2+could be a promising candidate for treating bacterial infections.
Development of Highly Potent Carbazole Amphiphiles as Membrane-Targeting Antimicrobials for Treating Gram-Positive Bacterial Infections
Lin, Shuimu,Liu, Jiayong,Li, Hongxia,Liu, Ying,Chen, Yongzhi,Luo, Jiachun,Liu, Shouping
, p. 9284 - 9299 (2020/10/19)
The development of new antimicrobial agents capable of curing drug-resistant bacteria-induced infections is becoming a major challenge to the global healthcare system. To develop antimicrobials with new molecular entities, a series of novel carbazole-based compounds were designed and synthesized by biomimicking the structural properties and biological function of antimicrobial peptides. Compound 29 was selected as a lead compound from the structure-activity relationship analyses and biological activity evaluation. Compound 29 showed excellent antimicrobial activity against Gram-positive bacteria (MICs = 0.78-1.56 μg/mL), poor hemolytic activity (HC50 > 200 μg/mL), and low cytotoxicity to mammalian cells. Compound 29 had fast bactericidal properties and effectively prevented bacterial resistance in laboratory simulations. Antibacterial mechanism studies revealed that compound 29 directly destroyed bacterial cell membranes, leading to bacterial deaths. Importantly, compound 29 displayed an excellent efficacy in a murine bacterial keratitis model caused by Staphylococcus aureus ATCC29213.
CARDIOTONIC COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST BETA-ADRENERGIC RECEPTORS AND PHOSPHODIESTERASE
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Page/Page column 63-64, (2010/11/08)
The present invention provides compounds possessing inhibitory activity against ? adrenergic receptors and phosphodiesterase (PDE), including type 3 phosphodiesterase (PDE-3). The present invention further provides pharmaceutical compositions comprising s
