Discovery of a potent enoyl-acyl carrier protein reductase (FabI) inhibitor suitable for antistaphylococcal agent.
We report the discovery, synthesis, and biological activities of phenoxy-4-pyrone and phenoxy-4-pyridone derivatives as novel inhibitors of enoyl-acyl carrier protein reductase (FabI). Pyridone derivatives showed better activities than pyrone derivatives against FabI and Staphylococcus aureus strains, including methicillin-resistant Staphylococcus aureus (MRSA). Among the pyridone derivatives, compound 16l especially exhibited promising activities against the MRSA strain and good pharmacokinetic profiles.
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Yun Gyeong
YG
Kim
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
Jae Hong
JH
Seo
School of Life and Food Sciences, Handong Global University, Pohang 791-7, Republic of Korea.
Jin Hwan
JH
Kwak
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, Republic of Korea. Electronic address: kyejung@catholic.ac.kr.
Kye Jung
KJ
Shin
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011728:Pyridones; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
Antibiotic; Enoyl-acyl carrier protein reductase (FabI); MRSA; Pyridone