Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors.

A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58-84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC50 1.80 ± 0.11 µM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC50 2.11 ± 0.31 µM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO2. However, size and position of the substituents affected enzyme inhibitions. . In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of -64.92,-203.25 and -140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values -170.91, -256.84 and -235.97 kcal/mol, respectively.

A library-screening approach for developing a fluorescence sensing array for the detection of metal ions.

Detection of individual metal ions is of importance across a range of fields of chemistry including environmental monitoring, and health and disease. Fluorescence is a highly sensitive technique and small fluorescent molecules are widely used for the detection and quantification of metal ions in various applications. Achieving specificity for a single metal from a single sensor is always a challenge. An alternative to selective sensing is the use of a number of non-specific sensors, in an array, which together respond in a unique pattern to each analyte. Here we show that screening a library of compounds can give a small sensor set that can be used to identify a range of metal ions following PCA and LDA. We explore a method for screening the initial compounds to identify the best performing sensors. We then present our method for reducing the size of the sensor array, resulting in a four-membered system, which is capable of identifying nine distinct metal ion species in lake water.

Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors.

A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71 ± 0.25 µM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 µM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 µM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 µM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as ΔG(bind) -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔG(bind) -9.04 and -8.51 kcal/mol, respectively, for BChE.

Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs.

A series of opioid and serotonin re-uptake inhibitors (SSRIs) bifunctional ligands have been designed, synthesized, and tested for their activities and efficacies at µ-, δ- and κ opioid receptors and SSRIs receptors. Most of the compounds showed high affinities for µ- and δ-opioid receptors and lower affinities for SSRIs and κ opioid receptors. A docking study on the µ-opioid receptor binding pocket has been carried out for ligands 3-11. The ligands 7 and 11 have displayed the highest binding profiles for the µ-opioid receptor binding site with ΔGbind (-12.14kcal/mol) and Ki value (1.0nM), and ΔGbind (-12.41kcal/mol) and Ki value (0.4nM), respectively. Ligand 3 was shown to have the potential of dual acting serotonin/norepinephrine re-uptake inhibitor (SNRI) antidepressant activity in addition to opioid activities, and thus could be used for the design of multifunctional ligands in the area of a novel approach for the treatment of pain and depression.