1.Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta.
Hebda M1, Bajda M2, Więckowska A3, Szałaj N4, Pasieka A5, Panek D6, Godyń J7, Wichur T8, Knez D9, Gobec S10, Malawska B11. Molecules. 2016 Mar 26;21(4). pii: E410. doi: 10.3390/molecules21040410.
Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer's disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention-compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM). Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE) (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM), and it inhibits amyloid beta aggregation (35.8% at 10 μM). Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase.
2.Organocatalytic Enantioselective Michael-Michael-Henry Reaction Cascade. An Entry to Highly Functionalized Hajos-Parrish-Type Ketones with Five to Six Contiguous Stereogenic Centers and Two Quaternary Carbons.
Raja A1, Hong BC1, Liao JH1, Lee GH2. Org Lett. 2016 Apr 15;18(8):1760-3. doi: 10.1021/acs.orglett.6b00459. Epub 2016 Mar 28.
An organocatalytic enantioselective reaction of 2-methylcyclopentane-1,3-dione, nitroalkene, and α,β-unsaturated aldehyde with the diphenylprolinol catalyst was developed to give the highly functionalized Hajos-Parrish-type ketones with five to six contiguous stereocenters and two quaternary carbon stereogenic centers with high diastereoselectivity and enantioselectivity. The structures of the adducts were unambiguously confirmed by single-crystal X-ray crystallographic analyses of the appropriate products.
3.Two-carbon ring expansion of isatin: a convenient construction of a dibenzo[b,d]azepinone scaffold.
Shi RG1, Wang XH1, Liu R1, Yan CG1. Chem Commun (Camb). 2016 Apr 15. [Epub ahead of print]
A unique two-carbon ring expansion of isatin has been achieved to conveniently construct the functionalized dibenzo[b,d]azepin-6-one scaffold in moderate to high yields, and the two carbon sources are different: one carbon is from the N-substituent of pyridinium bromide and the other is from indene-1,3-dione.
4.Characterization of Anticancer Principles of Celosia argentea (Amaranthaceae).
Rub RA1, Pati MJ2, Siddiqui AA1, Moghe AS3, Shaikh NN1. Pharmacognosy Res. 2016 Apr-Jun;8(2):97-104. doi: 10.4103/0974-8490.172659.
BACKGROUND: An Indian origin, Celosia argentea is a weed growing during rainy season traditionally claimed for treating several ailments. Early researches on C. argentea were focused on the anti-cancer screening of seeds, with few reports on aerial parts.