2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management.

BACKGROUND: Results of our previous studies on antiglycation activity, and the noncytotoxicity of 2-mercapto benzothiazoles, encouraged us to further widen our investigation towards the identification of leads against diabetes mellitus. METHODS: 33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro α- glucosidase inhibitory activity. Mode of inhibition was deduced by kinetic studies. To predict the interactions of 2-mercapto benzothiazole derivatives 1-33 with the binding pocket of α-glucosidase enzyme, molecular docking studies were performed on the selected inhibitors. RESULTS: Compounds 2-4, 6-7, 9-26, 28 and 30 showed many folds potent α-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 µM, as compared to the standard drug acarbose (IC50 = 875.75 ± 2.08 µM). It was important to note that except derivative 28, all other derivatives were also found previously to have antiglycating potential in the range of IC50 = 187.12-707.21 µM. CONCLUSION: A number of compounds were identified as dual nature as antiglycating agent and α- glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.

Electrooxidation of Pd-Cu NP loaded porous carbon derived from a Cu-MOF.

The development of new non-platinum catalysts for alcohol electrooxidation is of utmost importance. In this work, a bimetallic Pd-Cu loaded porous carbon material was first synthesized from a Cu-based metal-organic framework (MOF). The Cu loaded porous carbon was pre-synthesized through calcinating the Cu-based MOF under a N2 atmosphere. After loading Pd onto the precursor and heating, Pd-Cu loaded porous carbon (Pd-Cu/C) was obtained for alcohol electrooxidation. Electrooxidation experiments revealed that this Pd-Cu bimetal loaded porous carbon assisted steady state electrolysis for alcohol oxidation in alkaline media. Moreover, different alcohols were electrooxidated using the present electrocatalyst for the purposes of discussing the oxidation mechanism. This electrooxidation study of Pd-Cu/C derived from a MOF demonstrates a good understanding of the electrooxidation of different alcohols, and provides useful guidance for developing new electrocatalyst materials for energy conversion and electronic devices.

Facile synthesis of novel substituted aryl-thiazole (SAT) analogs via one-pot multi-component reaction as potent cytotoxic agents against cancer cell lines.

In this study, twenty-five (25) substituted aryl thiazoles (SAT) 1-25 were synthesized, and their in vitro cytotoxicity was evaluated against four cancer cell lines, MCF-7 (ER+ve breast), MDA-MB-231 (ER-ve breast), HCT116 (colorectal) and HeLa (cervical). The activity was compared with the standard anticancer drug doxorubicin (IC50=1.56±0.05µM). Among them, compounds 1, 4-8, and 19 were found to be toxic to all four cancer cell lines (IC50 values 5.37±0.56-46.72±1.80µM). Compound 20 was selectively active against MCF7 breast cancer cells with IC50 of 40.21±4.15µM, whereas compound 19 was active against MCF7 and HeLa cells with IC50 of 46.72±1.8, and 19.86±0.11µM, respectively. These results suggest that substituted aryl thiazoles 1 and 4 deserve to be further investigated in vivo as anticancer leads.

Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease.

A series of thirty (30) thiazole analogs were prepared, characterized by (1)H NMR, (13)C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59±0.01 and 389.25±1.75µM when compared with the standard eserine (IC50, 0.85±0.0001µM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59±0.01, 1.77±0.01, 6.21±0.01, 7.56±0.01, 8.46±0.01, 14.81±0.32 and 16.54±0.21µM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3±0.50, 35.3±0.64, 36.6±0.70, 44.81±0.81, 46.36±0.84, 48.2±0.06 and 48.72±0.91µM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.

Benzothiazole derivatives: novel inhibitors of methylglyoxal mediated glycation of proteins in vitro.

This manuscript describes the protein anti-glycation activity of thirty-three (33) benzothiazoles, out of which twenty-seven were the newly synthesized benzothiazoles. Compound 1 (IC50= 187 ± 2.6 µM) was found to be the most active, while compounds 2 (IC50= 219 ± 3.6 µM), 3 (IC50= 224 ± 1.9 µM), 4 (IC50= 223 ± 3.3 µM), 5 (IC50= 238 ± 2.2 µM), 7 (IC50= 266 ± 5.4 µM), 17 (IC50= 226 ± 1.6 µM) and 18 (IC50= 274 ± 2.4 µM) were significantly active, when compared with the standard rutin (IC50= 294 ± 1.5 µM). This study identified potential inhibitors of methylglyoxal mediated glycation of proteins, which is the pathophysiology of late diabetic complications.