122188-02-7Relevant articles and documents
Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
?ikla-Süzgün, Pelin,Kaushik-Basu, Neerja,Basu, Amartya,Arora, Payal,Talele, Tanaji T.,Durmaz, Irem,?etin-Atalay, Rengül,Kü?ükgüzel, ?. Güniz
, p. 778 - 785 (2015)
Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound.
Design, synthesis and biological evaluation of antitumor platinum(II) agents conjugated with non-steroidal anti-inflammatory drug species
Gou, Shaohua,Wang, Xinyi,Wang, Yuanjiang,Zang, Ju,Zhang, Bin
, (2022/02/02)
As one of the key features of tumor, inflammation attracts much attention of many researchers for antitumor study, in which non-steroidal anti-inflammatory drugs (NSAIDs) have been widely investigated in anti-inflammatory treatments in cancers. Herein, we report a series of novel platinum(II) complexes derived from conjugation of several NSAIDs derivatives with two antitumor platinum(II) agents. The antitumor inhibitory effects of the synthesized compounds on a number of cancer cell lines were estimated. By taking the advantage of two bioactive moieties, these compounds exhibited stronger antitumor activity than their parent platinum agents, and some appeared to have capability of overcoming cisplatin resistance. Among them, IA-1 showed the best cytotoxicity and even exhibited stronger antitumor activity than cisplatin. Further research indicated that IA-1 induced significant DNA damage and ROS generation, accompanied by high cellular platinum accumulation, resulting in a much higher apoptosis rate than cisplatin in A2780 cells. Moreover, IA-1 was found to inhibit metastasis and invasion of A2780 cells by suppressing the COX-2/JAK2/STAT3 axis. All these results revealed that introduction of NSAIDs species efficiently sensitized cancer cells to the synthetic compounds, proving that NSAIDs can enhance the activity of the platinum(II) agents via inhibiting inflammation in cancer cells.
Novel Etodolac-Based 1,2,4-Triazole Derivatives as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Study
Shaik,Rao,Venkatarao,Rao, S. V. M. Mohan,Kishore
, p. 2179 - 2187 (2021/02/09)
Abstract: A series of novel 1,2,4-triazole nonsteroidal anti-inflammatory drugs (NSAIDs)derived from etodolac were designed and synthesized. The synthesized compoundswere identified using 1H and13C NMR, IR, and mass spectra and elementalanalyses and evaluated for their in vitro antibacterial activity againstGram-positive microorganisms like Streptococcuspneumoniae and Klebsiellapneumoniae and Gram-negative strains such as Pseudomonas aeruginosa and Enterobacter cloacae with pefloxacin as a reference drug. Somecompounds showed a potent activity at a concentration 50 mg/mL with inhibitionzones of 30 to 36 mm against S. pneumoniae.Etodolac-derived N-isobutyl- and N-ethyl-1,2,4-triazoles containing4-methoxybenzylsulfanyl and 3-nitrobenzylsulfanyl groups were active againstP. aeruginosa with inhibition zones of25–29 mm at a concentration of 50 mg/mL. All compounds showed excellentantioxidant activity with IC50 values ranging from72.39±0.25 μg/mL to 16.39±0.65 μg/mL in comparison with ascorbic acid(IC50 16.81±0.18 μg/mL). Molecular docking studiesrevealed strong hydrogen bonding, π–π, and π–σ interactions of 3-nitro-,4-methoxy-, and 4-methylbenzyl moieties with Ser421, Val120, Tyr124, Phe319,Ala44, and Val120 amino acid residues of the active site of glycogen synthasekinase-3 (GSK-3) protein.
