- Aryloxycyclohexyl amide AMPK agonist as well as preparation method and medical application thereof
-
The invention discloses an aryloxy cyclohexyl amide AMPK agonist as well as a preparation method and medical application thereof. The AMPK agonist is specifically an aryloxy cyclohexyl amide compound as shown in a formula (I) or pharmaceutically acceptable salt or ester or solvate of the aryloxy cyclohexyl amide compound. The aryloxy cyclohexyl amide compound with the AMPK agonistic activity has remarkable agonistic activity on AMPK at the cellular level, and can effectively activate an AMPK signal channel in vivo, so that the aryloxy cyclohexyl amide compound can be used for preparing medicines for preventing or treating various AMPK-mediated diseases.
- -
-
Paragraph 0049; 0054-0055; 0207; 0209-0211
(2022/04/06)
-
- Design, synthesis, and biological evaluation of 3-amino-2-oxazolidinone derivatives as potent quorum-sensing inhibitors of Pseudomonas aeruginosa PAO1
-
Due to the increasing resistance of Pseudomonas aeruginosa to most clinically relevant antimicrobials, it is challenging to treat bacterial infection with traditional antibiotics. Quorum sensing can regulate the production of biofilms and virulence factors which are closely related to bacterial resistance. Previously we synthesized a series of oxazolidinone compounds targeting the quorum-sensing transcriptional regulatory protein CviR and ZS-12 showed good activity against Chromobacterium violaceum CV026 quorum-sensing. In this study, eighteen 3-amino-2-oxazolidinone compounds were designed and synthesized using ZS-12 as the lead compound. We initially evaluated the inhibitory activities of novel oxazolidinone compounds against QS using C. violaceum CV026 as a reporter strain. Thirteen compounds showed good activities (IC50 range 3.69–63.58 μM) and YXL-13 inhibition was the most significant (IC50 = 3.686 ± 0.5790 μM) against biofilm formation and virulence factors determination of P. aeruginosa PAO1. In vitro, YXL-13 significantly inhibited the formation of PAO1 biofilm (range 42.98%–17.67%), the production of virulence factors (pyocyanin, elastase, rhamnolipid, and protease), and bacterial motility. Moreover, the combination of YXL-13 with an antibiotic (meropenem trihydrate) could significantly improve the antibiotic susceptibility of biofilm P. aeruginosa PAO1 cells. In vivo, YXL-13 significantly prolonged the lifespan of wildtype Caenorhabditis elegans N2 infected by P. aeruginosa PAO1. In conclusion, YXL-13 is a candidate agent for antibiotic-resistant P. aeruginosa PAO1and provides a method for finding new antibacterial drugs.
- Jiang, Kai,Lin, Feng,Wu, Hao,Xiao, Junhai,Xiao, Zijian,Yan, Xinlin,Yu, Jiahao,Yue, Yuandong,Zhao, Meihua,Zhou, Xiaoping
-
-
- Piperazine adenosine monophosphate activated protein kinase (AMPK) agonist and medical application thereof
-
The invention discloses a piperazine compound with AMPK agonist activity, and a preparation method and medical application of the piperazine compound. The piperazine compound is a compound shown as aformula (I) (please see the specifications for the formula), and a pharmaceutically acceptable salt or ester or a prodrug or N-oxide or solvate thereof. The compound can be used for preparing drugs for preventing or treating AMPK-mediated diseases.
- -
-
Paragraph 0609; 0611; 0613
(2019/11/12)
-