An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.

The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized.

Hybridization of Fluoro-amodiaquine (FAQ) with Pyrimidines: Synthesis and Antimalarial Efficacy of FAQ-Pyrimidines.

To evade the possible toxicity associated with the formation of quinone-imine metabolite in amodiaquine (AQ), the -hydroxyl group was replaced with a -F atom, and the resulting 4'-fluoro-amodiaquine (FAQ) was hybridized with substituted pyrimidines. The synthesized FAQ-pyrimidines displayed better potency than chloroquine (CQ) against the resistant strain (Dd2), exhibiting up to 47.3-fold better activity (IC: 4.

Chemoselective Hydrazine-mediated Transfer Hydrogenation of Nitroarenes by Co O Nanoparticles Immobilized on an Al/Si-mixed Oxide Support.

Cobalt oxide nanoparticles (size 2 to 3.5 nm) were successfully impregnated on an alumina-silica (mixed oxide) support through an experimentally viable and easily reproducible protocol. The prepared material was well characterized by XRD, HR-TEM, BET surface area, EDX and XPS analyses.

N-Piperonyl substitution on aminoquinoline-pyrimidine hybrids: Effect on the antiplasmodial potency.

A series of 4-aminoquinoline-piperonyl-pyrimidine hybrids were synthesized with the aim of identifying compounds with enhanced antimalarial activity. All the synthesized molecules were evaluated in vitro against cultured Plasmodium falciparum W2 and D6 strains and exhibited potent antiplasmodial activities with IC values in the range of 0.02-5.

Design, synthesis and evaluation of 4-aminoquinoline-purine hybrids as potential antiplasmodial agents.

A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency.

4-aminoquinoline based molecular hybrids as antimalarials: an overview.

In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance problems. Towards this end, a lot of effort has been put for generating 4-aminoquinoline based hybrid molecules as next generation antimalarial drugs effective in malarial chemotherapy.