Design, synthesis and biological investigation of certain pyrazole-3-carboxylic acid derivatives as novel carriers for nitric oxide.
Some novel pyrazole-NO hybrid molecules 5a-e, 6, 8 and 10 were prepared through binding of the pyrazole-3-carboxylic acid derivatives with nitric oxide donor moiety like oxime or nitrate ester. The prepared compounds were evaluated for nitric oxide release, antibacterial and anti-inflammatory activities. The organic nitrate 10 exhibited the highest percentage of NO release using Griess diazotization method. Some of the prepared compounds exhibited remarkable antibacterial activity against Escherichia coli C-600, Pseudomonas aeruginosa, Bacillus subitilis and Staphylococcus aureus NCTC 6571 compared to ciprofloxacin. Most of the tested compounds showed significant anti-inflammatory activity compared to indomethacine using carrageenan induced paw edema method. In general, structural modification of compound 2 either to nitrate ester or oxime hybrids showed better anti-inflammatory with less ulcerogenic liability than their corresponding starting intermediates.
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
el-Shimaa M N
el-SM
Abdel-Hafez
Gamal el-Din A A
Gel-D
Abuo-Rahma
Mohamed
M
Abdel-Aziz
Mohamed F
MF
Radwan
Hassan H
HH
Farag
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats
C526242:3,5-pyrazoledicarboxylic acid; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids; D011720:Pyrazoles; D009569:Nitric Oxide