N-sulfonylanthranilic acid derivatives as allosteric inhibitors of dengue viral RNA-dependent RNA polymerase.
A novel class of compounds containing N-sulfonylanthranilic acid was found to specifically inhibit dengue viral polymerase. The structural requirements for inhibition and a preliminary structure-activity relationship are described. A UV cross-linking experiment was used to map the allosteric binding site of the compound on the viral polymerase.
Yin
Zheng
Z
Novartis Institute for Tropical Diseases, Chromos, 138670, Singapore.
Chen
Yen-Liang
YL
Kondreddi
Ravinder Reddy
RR
Chan
Wai Ling
WL
Wang
Gang
G
Ng
Ru Hui
RH
Lim
Joanne Y H
JY
Lee
Wan Yen
WY
Jeyaraj
Duraiswamy A
DA
Niyomrattanakit
Pornwaratt
P
Wen
Daying
D
Chao
Alex
A
Glickman
J Fraser
JF
Voshol
Hans
H
Mueller
Dieter
D
Spanka
Carsten
C
Dressler
Sigmar
S
Nilar
Shahul
S
Vasudevan
Subhash G
SG
Shi
Pei-Yong
PY
Keller
Thomas H
TH
D001665:Binding Sites; D003716:Dengue Virus / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013441:Sulfinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013441:Sulfinic Acids; D062367:ortho-Aminobenzoates; D012324:RNA-Dependent RNA Polymerase