3580-38-9Relevant articles and documents
Synthesis of small molecules targeting paclitaxel-induced MyD88 expression in triple-negative breast cancer cell lines
Poh Yen, Khor,Stanslas, Johnson,Zhang, Tianshu,Li, Hongyuan,Wang, Xiaohui,Kok Meng, Chan,Kok Wai, Lam
, (2021/10/04)
Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4? cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.
Generation and trapping of electron-deficient 1,2-cyclohexadienes. Unexpected hetero-Diels-Alder reactivity
Wang, Baolei,Constantin, Marius-Georgian,Singh, Simarpreet,Zhou, Yuqiao,Davis, Rebecca L.,West
supporting information, p. 399 - 405 (2021/01/29)
Keto-substituted 1,2-cyclohexadienes were generated by base-mediated (KOt-Bu) elimination, and found to dimerize via an unprecedented formal hetero-Diels-Alder process, followed by hydration. These highly reactive cyclic allene intermediates were also tra
Design and synthesis of a novel mPGES-1 lead inhibitor guided by 3D-QSAR CoMFA
Fasihi Mohd Aluwi, Mohd Fadhlizil,Rullah, Kamal,Koeberle, Andreas,Werz, Oliver,Abdul Razak, Nur Sakinah,Wei, Leong Sze,Salim, Fatimah,Ismail, Nor Hadiani,Jantan, Ibrahim,Wai, Lam Kok
, p. 844 - 850 (2019/07/12)
The search of novel mPGES-1 inhibitors has recently intensified probably due to the superior safety in comparison to existing anti-inflammatory drugs. Although two mPGES-1 inhibitors have entered clinical trials, none has yet reached the market. In this study, we performed modifications guided by 3D-QSAR CoMFA on 2, which is an unsymmetrical curcumin derivative with low binding affinity towards mPGES-1. To counter the PAINS properties predicted for 2, the diketone linker was replaced with a pyrazole ring. On the other hand, both prenyl and carboxylate ester groups were introduced to improve the activity. When tested in vitro, 11 suppressed PGE2 biosynthesis in activated macrophages and showed promising human mPGES-1 inhibition in microsomes of interleukin-1β-stimulated A549 cells. Altogether, 11 has been identified as a potential mPGES-1 inhibitor and could be a promising lead for a novel class of mPGES-1 inhibitors.
