77124-20-0Relevant articles and documents
Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy
Chen, Hekai,Kong, Jun,Li, Tian,Xu, Qun,Yin, Hang,Zhang, Liwei
supporting information, p. 1771 - 1779 (2021/11/19)
In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.
Multifunctional cinnamic acid derivatives
Peperidou, Aikaterini,Pontiki, Eleni,Hadjipavlou-Litina, Dimitra,Voulgari, Efstathia,Avgoustakis, Konstantinos
, (2017/09/01)
Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC50 = 6 uM) and antiproteolytic activity (IC50 = 0.425 uM). The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 uM) and good LOX inhibitory activity (IC50 = 66 uM). Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.
Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
supporting information, p. 6713 - 6716 (2013/10/01)
A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
