Synthesis and Biological Evaluation of Novel FtsZ-targeted 3-arylalkoxy-2,6-difluorobenzamides as Potential Antimicrobial Agents.
Novel series of 3-O-arylalkylbenzamide and 3-O-arylalkyl-2,6-difluorobenzamide derivatives were synthesized and evaluated for their on-target activity and antibacterial activity. The results indicated that the 3-O-arylalkyl-2,6-difluorobenzamide derivatives possessed much better on-target activity and antibacterial activity than the 3-O-arylalkylbenzamide derivatives. Among them, 3-O-chlorobenzyl derivative 36 was the most effective in antibacterial activity (0.5, 4, and 8 μg/mL) against Bacillus subtilis ATCC9372, methicillin-resistant Staphylococcus aureus ATCC29213, and penicillin-resistant Staphylococcus aureus PR, while 3-O-methylbenzyl derivative 41 only exhibited the most potent activity (2 μg/mL) against Staphylococcus aureus ATCC25923.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Shengsheng
S
Qiang
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Changde
C
Wang
School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.
Henrietta
H
Venter
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Xin
X
Li
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Yi
Y
Wang
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Liwei
L
Guo
Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China.
Ruixin
R
Ma
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, 250012, China.
Shutao
S
Ma
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects
D000890:Anti-Infective Agents; D001549:Benzamides; C078231:2,6-difluorobenzamide
2,6-difluorobenzamide; FtsZ inhibitors; antibacterial activity; on-target activity; synthesis