Citral derived amides as potent bacterial NorA efflux pump inhibitors.
Monoterpene citral and citronellal have been used as starting material for the preparation of 5,9-dimethyl-deca-2,4,8-trienoic acid amides and 9-formyl-5-methyl-deca-2,4,8-trienoic acid amides. The amides on bioevaluation as efflux pump inhibitors (EPIs) against Staphylococcus aureus 1199 and NorA overexpressing S. aureus 1199B bacteria resulted in the identification of several of these as potent EPIs. Many of these amides have been shown to possess potency higher or equivalent to known EPIs such as reserpine, verapamil, carsonic acid, and piperine. In this communication, we report a convenient synthesis of alkenyl amides, their bioevaluation and identification as efflux pump inhibitors against S. aureus.
Thota
Niranjan
N
Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu Tawi 180001, India.
Koul
Surrinder
S
Reddy
Mallepally V
MV
Sangwan
Payare L
PL
Khan
Inshad A
IA
Kumar
Ashwani
A
Raja
Alsaba F
AF
Andotra
Samar S
SS
Qazi
Ghulam N
GN
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002939:Ciprofloxacin / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000577:Amides; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus