Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages.
A novel series of diphenolic chromone derivatives were synthesized and their inhibitory activity on nitric oxide (NO) production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, (5,7-dihydroxy-4-oxo-4H-chromen-3-yl) methyl esters (6b, 6c, 6f, 6g, and 6h) showed quite potent inhibitory activities with IC(50) values of 2.20, 3.48, 0.35, 0.80, and 0.61microM, respectively. The MTT results showed that all of the active compounds exhibited no cytotoxicity at the effective concentrations. The preliminary mechanism of the most potent compounds (6b, 6c, 6f, 6g, and 6h) was further examined based on the RT-PCR results and the compounds 6f, 6g, and 6h inhibited NO production by suppressing the expression of iNOS mRNA in a dose dependent manner. Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug-like properties.
Liu
Guo-Biao
GB
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
Xu
Jian-Liang
JL
Geng
Mei
M
Xu
Rui
R
Hui
Rong-Rong
RR
Zhao
Jian-Wei
JW
Xu
Qiang
Q
Xu
Hong-Xi
HX
Li
Jian-Xin
JX
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II