63450-46-4Relevant academic research and scientific papers
Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
Yu, Haonan,Hou, Zhuang,Tian, Ye,Mou, Yanhua,Guo, Chun
, p. 434 - 449 (2018/04/14)
To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.
Substrate specificity of acetoxy derivatives of coumarins and quinolones towards Calreticulin mediated transacetylation: Investigations on antiplatelet function
Kathuria, Abha,Priya, Nivedita,Chand, Karam,Singh, Prabhjot,Gupta, Anjali,Jalal, Sarah,Gupta, Shilpi,Raj, Hanumantharao G.,Sharma, Sunil K.
, p. 1624 - 1638 (2012/05/04)
Calreticulin transacetylase (CRTAase) is known to catalyze the transfer of acetyl group from polyphenolic acetates (PA) to certain receptor proteins (RP), thus modulating their activity. Herein, we studied for the first time the substrate specificity of CRTAase towards N-acetylamino derivatives of coumarins and quinolones. This study is endowed with antiplatelet action by virtue of causing CRTAase catalyzed activation of platelet Nitric Oxide Synthase (NOS) by way of acetylation leading to the inhibition of ADP/Arachidonic acid (AA)-dependent platelet aggregation. Among all the N-acetylamino/acetoxy coumarins and quinolones screened, 7-N-acetylamino-4-methylcoumarin (7-AAMC, 17) was found to be the superior substrate to platelet CRTAase and emerged as the most promising antiplatelet agent both in vitro and in vivo. Further it caused the inhibition of cyclooxygenase-1 (Cox-1) resulting in the down regulation of thromboxane A2 (TxA2), modulation of tissue factor and the inhibition of platelet aggregation. It was also found effective in the inhibition of LPS induced pro-thrombotic conditions.
Synthesis and Chemistry of 7-Amino-4-(trifluoromethyl)coumarin and Its Amino Acid and Peptide Derivatives
Bissell, Eugene R.,Mitchell, Alexander R.,Smith, Robert E.
, p. 2283 - 2287 (2007/10/02)
The synthesis and purification of 7-amino-4-(trifluoromethyl)coumarin, a novel fluorescent marker for the sensitive detection of proteinases, were investigated.Two byproducts, 7-hydroxy-4-(trifluoromethyl-2-quinolone and 2-ethoxy-7-hydroxy-4-(trifluoromethyl)quinoline, were isolated and identified. 7-Methoxy-4-(trifluoromethyl)-2-quinolone was also prepared.Amino acid and peptide derivatives prepared by solution methods using the stepwise approach included 7-(L-leucinamido)-, 7-(D-alanyl-L-leucyl-L-lysinamido)-, 7-(D-valyl-L-leucyl-L-lysinamido)-, and 7-(Nα-Z-glycylglycyl-L-argininamido)-4-(trifluoromethyl)coumarins
