No abstract

A chitosan-based magnetic nanocomposite was synthesized by an eco-friendly and simple procedure, and was characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy. It was then used for the efficient synthesis of tetrahydrobenzoxanthen-11-one derivatives via a one-pot three-component condensation of 2-naphthol, various aldehydes and dimedone in ethanol. The catalyst was recovered easily and reused several times without significant loss of catalytic activity.

An environmentally benign and clean biopolymer-based heterogeneous nanocatalyst was prepared and its properties and morphology were characterized using scanning electron microscopy (SEM), energydispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). Then, its catalytic activity was investigated in two important organic reactions. In these reactions, efficient and selective syntheses of 1,2-disubstituted benzimidazole and 1,5-benzodiazepine derivatives were carried out using 1,2-diamines and aldehydes or ketones in the presence of a catalytic amount of magnetically recoverable chitosansupported iron oxide nanoparticles (Fe 3 O 4 /chitosan), as a biodegradable nanocomposite, in ethanol at ambient temperature in high yields. The Fe 3 O 4 /chitosan nanocatalyst can be recovered easily and reused without any significant loss of the catalytic activity.

A practical and green approach for the one-pot multicomponent synthesis of tetraheterocyclic benzimidazolo[2,3-b]quinazolinones has been described via the condensation of 2-aminobenzimidazole or 2-aminobenzothiazole, dimedone, and various aldehydes using Fe3O4@chitosan as an environmentally benign and reusable nanocomposite catalyst in good to excellent yields.

Histamine H3 receptors (H3R), belonging to G‐protein coupled receptors (GPCR) class A superfamily, are responsible for modulating the release of histamine as well as of other neurotransmitters by a negative feedback mechanism mainly in the central nervous system (CNS). These receptors have gained increased attention as therapeutic target for several CNS related neurological diseases. In the current study, we aimed to identify novel H3R ligands using in silico virtual screening methods. To this end, a combination of ligand‐ and structure‐based approaches was utilized for screening of ZINC database on the homology model of human H3R. Structural similarity‐ and pharmacophore‐based approaches were employed to generate compound libraries. Various molecular modeling methodologies such as molecular docking and dynamics simulation along with different drug likeness filtering criteria were applied to select anti‐H3R ligands as promising candidate molecules based on different known parent lead compounds. In vitro binding assays of the selected molecules demonstrated three of them being active within the micromolar and submicromolar Ki range. The current integrated computational and experimental methods used in this work can provide new general insights for systematic hit identification for novel anti‐H3R agents from large compound libraries.

Recently, multi-target directed ligands have been of research interest for multifactorial disorders such as Alzheimer's disease (AD). Since H 3 receptors (H 3 Rs) and cholinesterases are involved in pathophysiology of AD, identification of dual-acting compounds capable of improving cholinergic neurotransmission is of importance in AD pharmacotherapy. In the present study, H 3 R antagonistic activity combined with anticholinesterase properties of two previously computationally identified leadpropyl]-1H-indole-2-carboxamide) and compound 4 (7-chloro-N-[(1-methylpiperidin-3-yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-carboxamide), was tested.Moreover, molecular docking and binding free energy calculations were conducted for binding mode and affinity prediction of studied ligands toward cholinesterases. Biological evaluations revealed inhibitory activity of ligands in nanomolar (com-pound 3: H 3 R EC 50 = 0.73 nM; compound 4: H 3 R EC 50 = 31 nM) and micromolar values (compound 3: AChE IC 50 = 9.09 µM, BuChE IC 50 = 21.10 µM; compound 4: AChE IC 50 = 8.40 µM, BuChE IC 50 = 4.93 µM) for H 3 R antagonism and cholinesterase inhibition, respectively. Binding free energies yielded good consistency with cholinesterase inhibitory profiles. The results of this study can be used for lead optimization where dual inhibitory activity on H 3 R and cholinesterases is needed. Such ligands can exert their biological activity in a synergistic manner resulting in higher potency and efficacy. K E Y W O R D S anticholinesterase, anti-H 3 R agents, histamine H 3 receptor, molecular docking, molecular dynamics simulation, multi-target directed ligands 280 | GHAMARI et Al.

A simple and convenient approach for the synthesis of tetraheterocyclic benzimidazolo [2,3-b]quinazolin-1-ones has been developed via a multicomponent reaction, which involves the condensation of 2-aminobenzimidazole, dimedone and various aldehydes using chitosan-supported metal nanocomposite as a green, reusable and environmentally benign catalyst system. Environmental friendly, recyclability, cost-effectiveness, easy workup and excellent yields are the major attributes of this one-pot procedure.

Benzodiazepines. -A magnetically recoverable and biodegradable heterogeneous nanocatalyst is prepared and characterized. This catalyst efficiently catalyzes the synthesis of 1,2-disubstituted benzimidazoles from 1,2-diamines and aryl aldehydes. When ketones [(VI) and (IX)] are used, 1,5-benzodiazepines can be obtained. The catalyst can be easily recovered and reused for 6 times without significant loss of the catalytic activity. -(MALEKI*, A.; GHAMARI, N.; KAMALZARE, M.; RSC Adv. 4 (2014) 19, 9416-9423, http://dx.doi.org/10.1039/c3ra47366j ; Dep. Chem., Iran Univ. Sci. Technol., Tehran, Iran; Eng.) -L. Grundl 39-062