58950-89-3Relevant articles and documents
Iminophosphorane-Mediated Synthesis of the Fascaplysin Alkaloid of Marine Origin and Nitramarine
Molina, Pedro,Fresneda, Pilar M.,Garcia-Zafra, Sagrario,Almendros, Pedro
, p. 8851 - 8854 (1994)
New and efficient syntheses of the fascaplysin alkaloid of marine origin and nitramarine are described.In both syntheses the key step, formation of the β-carboline ring, involve a tandem aza-Wittig/electrocyclic ring closure process.
Mono- or di-substituted imidazole derivatives for inhibition of acetylcholine and butyrylcholine esterases
Kuzu, Burak,Tan, Meltem,Taslimi, Parham,Gül?in, ?lhami,Ta?p?nar, Mehmet,Menges, Nurettin
, p. 187 - 196 (2019/02/06)
Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 μM, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 μM.
Quinoxaline derivatives: Novel and selective butyrylcholinesterase inhibitors
Zeb, Aurang,Hameed, Abdul,Khan, Latifullah,Khan, Imran,Dalvandi, Kourosh,Choudhary, M. Iqbal,Basha, Fatima Z.
, p. 724 - 729 (2015/04/14)
Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against achymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0μM) and 7 (IC50 = 9.7 ± 0.9 μM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 μM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
