3529-10-0Relevant articles and documents
Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents
Patel, Dushyant V.,Patel, Nirav R.,Kanhed, Ashish M.,Patel, Sagar P.,Sinha, Anshuman,Kansara, Deep D.,Mecwan, Annie R.,Patel, Sarvangee B.,Upadhyay, Pragnesh N.,Patel, Kishan B.,Shah, Dharti B.,Prajapati, Navnit K.,Murumkar, Prashant R.,Patel, Kirti V.,Yadav, Mange Ram
, p. 3635 - 3661 (2019/08/20)
The multifaceted nature of Alzheimer's disease (AD) demands treatment with multitarget-directed ligands (MTDLs) to confront the key pathological aberrations. A novel series of triazinoindole derivatives were designed and synthesized. In vitro studies revealed that all the compounds showed moderate to good anticholinesterase activity; the most active compound 23e showed an IC50 value of 0.56 ± 0.02 μM for AChE and an IC50 value of 1.17 ± 0.09 μM for BuChE. These derivatives are also endowed with potent antioxidant activity. To understand the plausible binding mode of the compound 23e, molecular docking studies and molecular dynamics simulation studies were performed, and the results indicated significant interactions of 23e within the active sites of AChE as well as BuChE. Compound 23e successfully diminished H2O2-induced oxidative stress in SH-SY5Y cells and displayed excellent neuroprotective activity against H2O2 as well as Aβ-induced toxicity in SH-SY5Y cells in a concentration dependent manner. Furthermore, it did not show any significant toxicity in neuronal SH-SY5Y cells in the cytotoxicity assay. Compound 23e did not show any acute toxicity in rats at doses up to 2000 mg/kg, and it significantly reversed scopolamine-induced memory deficit in mice model. Additionally, compound 23e showed notable in silico ADMET properties. Taken collectively, these findings project compound 23e as a potential balanced MTDL in the evolution process of novel anti-AD drugs.
OMEGA-AMINOALKYLAMIDES OF (R)-2-ARYL-PROPIONIC ACIDS AS INHIBITORS OF THE CHEMOTAXIS OF POLYMORPHONUCLEATE AND MONONUCLEATE CELLS
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Paragraph 0081, (2016/08/23)
no abstract published
Cytotoxic Glycosylated Fatty Acid Amides from a Stelletta sp. Marine Sponge
Peddie, Victoria,Takada, Kentaro,Okuda, Shujiro,Ise, Yuji,Morii, Yasuhiro,Yamawaki, Nobuhiro,Takatani, Tomohiro,Arakawa, Osamu,Okada, Shigeru,Matsunaga, Shigeki
supporting information, p. 2808 - 2813 (2015/12/09)
We have discovered new glycosylated fatty acid amides, stellettosides, from a Stelletta sp. marine sponge. They were detected through LC-MS analysis of the extract combined with the cytotoxicity assay of the prefractionated sample. Their planar structures were determined by analyses of the NMR and tandem FABMS data. Stellettosides A1 and A2 (1 and 2) as well as stellettosides B1-B4 (3-6) were obtained as inseparable mixtures. Careful analysis of the NMR and tandem FABMS data of each mixture, along with comparison of the tandem FABMS data with that of a synthetic model compound, permitted us to assign the structure of the constituents in the mixture. The absolute configuration of the monosaccharide unit was determined by LC-MS after chiral derivatization. The relative configurations of the vicinal oxygenated methines in the fatty acid chains were assigned by the 1H NMR data of the isopropylidene derivative. The mixture of stellettosides B1-B4 (3-6) exhibit moderate cytotoxic activity against HeLa cells with an IC50 value of 9 ΜM, whereas the mixture of stellettosides A1 and A2 (1 and 2) was not active at a concentration of 10 ΜM.
