Creating an antibacterial with in vivo efficacy: synthesis and characterization of potent inhibitors of the bacterial cell division protein FtsZ with improved pharmaceutical properties.
3-Methoxybenzamide (1) is a weak inhibitor of the essential bacterial cell division protein FtsZ. Alkyl derivatives of 1 are potent antistaphylococcal compounds with suboptimal drug-like properties. Exploration of the structure-activity relationships of analogues of these inhibitors led to the identification of potent antistaphylococcal compounds with improved pharmaceutical properties.
Haydon
David J
DJ
Biota Europe Ltd., Begbroke Science Park, Yarnton, Oxfordshire, UK. d.haydon@biota.com.au
Bennett
James M
JM
Brown
David
D
Collins
Ian
I
Galbraith
Greta
G
Lancett
Paul
P
Macdonald
Rebecca
R
Stokes
Neil R
NR
Chauhan
Pramod K
PK
Sutariya
Jignesh K
JK
Nayal
Narendra
N
Srivastava
Anil
A
Beanland
Joy
J
Hall
Robin
R
Henstock
Vincent
V
Noula
Caterina
C
Rockley
Chris
C
Czaplewski
Lloyd
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; C531944:PC190723; D011725:Pyridines; D013844:Thiazoles