90818-60-3Relevant articles and documents
Synthesis and anthelmintic activity of coumarin–imidazole hybrid derivatives against Dactylogyrus intermedius in goldfish
Liu, Guang-Lu,Hu, Yang,Chen, Xiao-Hui,Wang, Gao-Xue,Ling, Fei
, p. 5039 - 5043 (2016)
With an intention to find more potent anti-parasite agents, four bromoalkane substituted coumarin derivatives (1–4) and twenty coumarin–imidazole hybrid derivatives were synthesized and screened for their anthelmintic activity and the acute toxicity. Anti-parasites results confirmed that most coumarin derivatives retained their anthelmintic activity against Dactylogyrus intermedius at the dose range from 1 to 10?mg/L. Among the candidates, compound 23 showed the best anthelmintic activity than other compounds against D. intermedius infestation with EC50value of 0.85?mg/L. The structure–activity relationship analysis confirmed that the anthelmintic activities of derivatives were determined by the length of ‘linker’ (R1substitute position) and the substitute group in R2position. The active data confirmed that six carbon atoms length of ‘linker’ and benzimidazole substitute group can increased the anthelmintic activity of compound, significantly. On the basis of these results, compound 23 can be used as a potential lead compound for the development of commercial drug against D. intermedius.
Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway
Shang, Fan-Fan,Wang, Jing Ying,Xu, Qian,Deng, Hao,Guo, Hong-Yan,Jin, Xuejun,Li, Xiaoting,Shen, Qing-Kun,Quan, Zhe-Shan
, (2021/05/03)
Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, compound C6 exhibited the best features: firstly, the strongest HIF-1α inhibitory activity (IC50 = 0.05 μM, 5-fold higher than that of celastrol); secondly, lower cytotoxicity (22-fold lower, C6-16.85 μM vs celastrol-0.76 μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that C6 may inhibit the expression of HIF-1α protein in cells. Additionally, C6 hindered tumor cell cloning, migration and induced cell apoptosis. It is worth mentioning that in the mouse tumor xenograft model, C6 (10 mg/kg) displayed good antitumor activity in vivo, showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, C6 minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of C6 is increased by 1.36 times than that of celastrol. In conclusion, C6 is a promising antitumor agent through HIF-1α pathway.
New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation
Arora, Saroj,Attri, Shivani,Bhagat, Kavita,Kaur Gulati, Harmandeep,Kaur, Prabhjot,Kumar, Nitish,Mohinder Singh Bedi, Preet,Sharma, Sahil,Singh, Atamjit,Singh, Harbinder,Vir Singh, Jatinder
, (2020/08/17)
A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Aβ1-42 aggregation inhibition (34.26% at 50 μΜ) and chelating properties for metal ions (Cu2+, Fe2+, and Zn2+) involved in AD pathogenesis along with DNA protective potential against degenerative actions of [rad]OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Aβ1-42 monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer's agents.
