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Nature Chemistry 9, 874 (2017). doi:10.1038/nchem.2754

Authors: Jan Stöhr, Haifan Wu, Mimi Nick, Yibing Wu, Manasi Bhate, Carlo Condello, Noah Johnson, Jeffrey Rodgers, Thomas Lemmin, Srabasti Acharya, Julia Becker, Kathleen Robinson, Mark J. S. Kelly, Feng Gai, Gerald Stubbs, Stanley B. Prusiner & William F. DeGrado

The self-propagation of misfolded conformations of tau occurs in neurodegenerative diseases, including Alzheimer's disease. The microtubule-binding region, tau244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Now, it has been shown that a 31-residue peptide from tau's R3 domain forms a cross-β conformation that efficiently seeds aggregation of tau244-372 in cells.

Abstract

Publication date: 3 February 2016
Source:Tetrahedron Letters, Volume 57, Issue 5
Author(s): Srinivasarao Yaragorla, Garima Singh, Ravikrishna Dada
A catalyst-free and green approach of sp³ C–H functionalization of methyl azaarenes with malononitrile and isatins for the synthesis of oxindole derivatives bearing quaternary carbon center has been described in water. This one-pot three component synthesis endures the key features like first ‘on water synthesis’, short reaction times, moderate to good yields, and large substrate scope.

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Publication date: 20 January 2016
Source:Tetrahedron Letters, Volume 57, Issue 3
Author(s): Ahmad Shaabani, Seyyed Emad Hooshmand, Azadeh Tavousi Tabatabaei
The diversity-oriented synthesis of a naphthyridine scaffold has been demonstrated via a novel domino four-component reaction. The syntheses were achieved by reacting a diamine, 1,1-bis(methylthio)-2-nitroethylene, 2-aminoprop-1-ene-1,1,3-tricarbonitrile, and various carbonyl compounds using a deep eutectic solvent (DES), based on choline chloride/urea, thus providing a new class of poly-functionalized fused naphthyridine derivatives with the concomitant formation of three new rings and six σ bonds. The reaction conditions were mild and did not require additional base catalysts. Given the inexpensive, nontoxic, and recyclable nature of the DES, these reaction conditions are simple and highly environmentally friendly.

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Publication date: 1 October 2015
Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 19
Author(s): Amitabh Jha, Katherine M. Duffield, Matthew R. Ness, Sujatha Ravoori, Gabrielle Andrews, Khushwant S. Bhullar, H.P. Vasantha Rupasinghe, Jan Balzarini
Three series of novel 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones, designed as simplified analogs of curcumin with maleic diamide tether, were synthesized and bioevaluated. These compounds displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemic cells. In contrast, the related N-arylmaleamic acids possessed little or no cytotoxicity in these three screens. Design of these compounds was based on molecular modeling studies performed on a related series of molecule in a previous study. Representative title compounds were found to be significantly potent in inhibiting the activity of topoisomerase II alpha indicating the possible mode of action of these compounds. These compounds were also potent antioxidants in vitro and attenuated the AAPH triggered peroxyl radical production in human fibroblasts. Various members of these series were also well tolerated in both in vitro and in vivo toxicity analysis.

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