The mode of antibacterial action of the novel agent ZM240304 (D-arabino-2,3,4-tris(4-chlorobenzyl) pentane-1,5-diamine).
ZM240304 is an example of a new class of antibacterial agents that is active against experimental infections in animals. The compound was demonstrated to be a membrane-active compound that disrupted the outer membrane of Gram-negative organisms and allowed the leakage of periplasmic enzymes. Respiration was inhibited and cellular ATP levels were reduced, leading to cell death. The ability of the bacteria to take up small molecules such as amino acids and sugars was inhibited, probably by interference with inner membrane function.
Barrett-Bee
K
K
Department of Infection, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Newboult
L
L
Stawpert
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010101:Oxygen Consumption / Q000187:drug effects; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D003959:Diamines; D010647:Phenyl Ethers; C105014:ZM 240304; D000255:Adenosine Triphosphate