3580-38-9Relevant articles and documents
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
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.
The involvement of l-arginine-nitric oxide-cgmp-atp-sensitive k+ channel pathway in antinociception of bbhc, a novel diarylpentanoid analogue, in mice model
Abas, Faridah,Ahmad Azmi, Ahmad Farhan,Farouk, Ahmad Akira Omar,Israf, Daud Ahmad,Leong, Sze Wei,Ong, Hui Ming,Perimal, Enoch Kumar,Sulaiman, Mohd Roslan
, (2021/12/24)
The present study focuses on the possible involvement of L-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperi-toneal pre-treatment of L-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K+ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC’s antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p + channel pathway, without any potential sedative or muscle relaxant concerns.
Three-Component Coupling of Acyl Fluorides, Silyl Enol Ethers, and Alkynes by P(III)/P(V) Catalysis
Fujimoto, Hayato,Kusano, Momoka,Kodama, Takuya,Tobisu, Mamoru
supporting information, p. 18394 - 18399 (2021/11/22)
We report herein on the phosphine-catalyzed hydrovinylation reaction by three-component coupling of acyl fluorides, silyl enol ethers, and alkynoates. The key to the success of the reaction is the formal transmetalation between pentacoordinate P(V) species (i.e., fluorophosphorane) and a silyl enol ether, which allows for C-C bond formation between the polarity-mismatched sites. The bond formation that cannot be attained even by transition metal catalysis is accomplished by a P(III)/P(V) manifold.
Synthesis of 1,3-Diketones and β-Keto Thioesters via Soft Enolization
Aderibigbe, Sabrina O.,Coltart, Don M.
, p. 9770 - 9777 (2019/08/27)
Ketones and thioesters undergo soft enolization and acylation using crude acid chlorides on treatment with MgBr2·OEt2 and i-Pr2NEt to give 1,3-diketones and β-keto thioesters, respectively. The use of crude acid chlorides adds efficiency and cost reduction by avoiding the need to purify and/or purchase them. The process is conducted in a direct fashion that does not require prior enolate formation, further enhancing its efficiency and making it very easy to carry out. The method is suitable for large scale applications. ?
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.
In vitro and in silico evaluations of diarylpentanoid series as α-glucosidase inhibitor
Leong, Sze Wei,Abas, Faridah,Lam, Kok Wai,Yusoff, Khatijah
, p. 302 - 309 (2018/01/03)
A series of thirty-four diarylpentanoids derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity. Eleven compounds (19, 20, 21, 24, 27, 28, 29, 31, 32, 33 and 34) were found to significantly inhibit α-glucosidase in which compounds 28, 31 and 32 demonstrated the highest activity with IC50 values ranging from 14.1 to 15.1 μM. Structure-activity comparison shows that multiple hydroxy groups are essential for α-glucosidase inhibitory activity. Meanwhile, 3,4-dihydroxyphenyl and furanyl moieties were found to be crucial in improving α-glucosidase inhibition. Molecular docking analyses further confirmed the critical role of both 3,4-dihydroxyphenyl and furanyl moieties as they bound to α-glucosidase active site in different mode. Overall result suggests that diarylpentanoids with both five membered heterocyclic ring and polyhydroxyphenyl moiety could be a new lead design in the search of novel α-glucosidase inhibitor.
Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
Mohd Aluwi, Mohd Fadhlizil Fasihi,Rullah, Kamal,Haque, Md. Areeful,Yamin, Bohari M.,Ahmad, Waqas,Amjad, Muhammad Wahab,Leong, Sze Wei,Fahmizar, Nurul Amira,Jalil, Juriyati,Abas, Faridah,Ismail, Nor Hadiani,Jantan, Ibrahim,Lam, Kok Wai
, p. 3323 - 3335 (2017/10/06)
Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogen-activated protein kinase and NF-κβ pathways. As part of our continuing effort to search for new anti-inflammatory agents with better in vitro and in vivo efficacies, we have synthesized a series of new unsymmetrical dicarbonyl curcumin derivatives and tested their effects on prostaglandin E2 secretion level in interferon-γ/lipopolysaccharide-activated macrophage cells. Among those, five compounds exhibited remarkable suppression on prostaglandin E2 production with IC50 values ranging from 0.87 to 18.41 μM. The most potent compound 17f was found to down-regulate the expression of cyclooxygenase-2 mRNA suggesting that this series of compounds could possibly target the mitogen-activated protein kinase signal transduction pathway. Whilst the compound did not affect the expression of the conventional mitogen-activated protein kinases, the results suggest that it could disrupt the phosphorylation and activation of the proteins particularly the c-Jun N-terminal kinases. Finally, the binding interactions were examined using the molecular docking and dynamics simulation approaches.
Trimethylchlorosilane-Mediated Mild α-Chlorination of 1,3-Dicarbonyl Compounds Promoted by Phenyliodonium Diacetate
Chong, Siying,Su, Yingpeng,Wu, Lili,Zhang, Weigang,Ma, Junyan,Chen, Xiaowei,Huang, Danfeng,Wang, Ke-Hu,Hu, Yulai
supporting information, p. 1359 - 1370 (2016/05/02)
Trimethylchlorosilane was used as chlorine source for the α-chlorination of 1,3-dicarbonyl compounds with phenyliodonium diacetate as oxidant at room temperature. The reaction allows the selective synthesis of α-monochlorinated products from different kinds of 1,3-dicarbonyl compounds in good yield. The potential possibility of this conversion for bromination has also been investigated.
2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase
Leong, Sze Wei,Abas, Faridah,Lam, Kok Wai,Shaari, Khozirah,Lajis, Nordin H.
, p. 3742 - 3751 (2016/07/20)
In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50values of 1.6?μM and 0.6?μM, respectively. Further structure–activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes’ inhibition. The Lineweaver–Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer.
