Exploration of click reaction for the synthesis of modified nucleosides as chitin synthase inhibitors.
Click reaction approach toward the synthesis of two sets of novel 1,2,3-triazolyl linked uridine derivatives 19a-19g and 21a-21g was achieved by Cu(I)-catalyzed 1,3-dipolar cycloaddition of 5'-azido-5'-deoxy-2',3'-O-(1-methylethylidene)uridine (17) with propargylated ether of phenols 18a-18g and propargylated esters 20a-20g. Structure of one of the representative compound 19d was unambiguously confirmed by X-ray crystallography. Chitin synthase inhibition study of all these compounds 19a-19g and 21a-21g was carried out to develop antifungal strategy. Compounds 19d, 19e, 19f, and 21f were identified as potent chitin synthase inhibitors by comparing with nikkomycin. Compounds 19a, 19b, 19c, 19d, 21a, and 21b showed good antifungal activity against human and plant pathogens. Compounds 19a, 19b, 19f, 21c, 21f, and 21g were identified as lead chitin synthase inhibitors for further modifications by comparing results of inhibition of growth, % germ tube formation and chitin synthase activity.
Chaudhary
Preeti M
PM
Division of Organic Chemistry, National Chemical Laboratory, Pune 411 008, India.
Chavan
Sayalee R
SR
Shirazi
Fazal
F
Razdan
Meenakshi
M
Nimkar
Prachi
P
Maybhate
Shailaja P
SP
Likhite
Anjali P
AP
Gonnade
Rajesh
R
Hazara
Braja G
BG
Deshpande
Mukund V
MV
Deshpande
Sunita R
SR
D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009705:Nucleosides; D002687:Chitin Synthase