Dataset Information

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

ABSTRACT: In the present study, a series of new hydrazone and sulfonamide derivatives of 1,2,4-triazole were synthesized. Initially three 4-substituted-5-(2-pyridyl)-1,2,4-triazole-3-thiones ZE-1(a-c) were treated with ethyl chloroacetate to get the corresponding thioesters ZE-2(a-c), which were reacted with hydrazine hydrate to the respective hydrazides ZE-3(a-c). The synthesized hydrazides were condensed with different aldehydes and p-toluene sulfonylchloride to furnish the target hydrazone derivatives ZE-4(a-c) and sulfonamide derivatives ZE-5(a-c) respectively. All the synthesized compounds were characterized by FTIR, 1HNMR, 13CNMR and elemental analysis data. Furthermore, the new hydrazone and sulfonamide derivatives ZE-4(b-c) and ZE-5(a-b) were evaluated for their antiplatelet and anticoagulant activities. ZE-4b, ZE-4c, ZE-5a and ZE-5b inhibited arachidonic acid, adenosine diphosphate and collagen-induced platelets aggregation with IC50 values of 40.1, 785 and 10.01 (ZE-4b), 55.3, 850.4 and 10 (ZE-4c), 121.6, 956.8 and 30.1 (ZE-5a), 99.9, 519 and 29.97 (ZE-5b) respectively. Test compounds increased plasma recalcification time (PRT) and bleeding time (BT) with ZE-4c being found most effective, which at 30, 100, 300 and 1000 µM increased PRT to 84.2 ± 1.88, 142 ± 3.51, 205.6 ± 5.37 and 300.2 ± 3.48 s and prolonged BT to 90.5 ± 3.12, 112.25 ± 2.66, 145.75 ± 1.60 s (P < 0.001 vs. saline group) respectively. In silico docking approach was also applied to screen these compounds for their efficacy against selected drug targets of platelet aggregation and blood coagulation. Thus in silico, in vitro and in vivo investigations of ZE-4b, ZE-4c, ZE-5a and ZE-5b prove their antiplatelet and anticoagulant potential and can be used as lead molecules for further development.

SUBMITTER: Khalid W

PROVIDER: S-EPMC5801135 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Khalid Waseem W Badshah Amir A Khan Arif-Ullah AU Nadeem Humaira H Ahmed Sagheer S

Chemistry Central journal 20180207 1

In the present study, a series of new hydrazone and sulfonamide derivatives of 1,2,4-triazole were synthesized. Initially three 4-substituted-5-(2-pyridyl)-1,2,4-triazole-3-thiones ZE-1(a-c) were treated with ethyl chloroacetate to get the corresponding thioesters ZE-2(a-c), which were reacted with hydrazine hydrate to the respective hydrazides ZE-3(a-c). The synthesized hydrazides were condensed with different aldehydes and p-toluene sulfonylchloride to furnish the target hydrazone derivatives ...[more]

PMID: 29411174

Similar Datasets

Project description:There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. The currently available antidiabetic therapies are long-term complicated and side effect-prone, and this has led to a demand for more affordable and more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. In this research work, we have focused our efforts to synthesize a series of 1,2,4-triazole-based bis-hydrazones and evaluated their antidiabetic properties. In addition, the precise structures of the synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR, and HREI-MS. To find the antidiabetic potentials of the synthesized compounds, in vitro α-glucosidase and α-amylase inhibitory activities were characterized using acarbose as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both α-amylase and α-glucosidase enzymes was due to the different substitution patterns of the substituent(s) at variable positions of both aryl rings A and B. The results of the antidiabetic assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 0.70 ± 0.05 to 35.70 ± 0.80 μM (α-amylase) and 1.10 ± 0.05 to 30.40 ± 0.70 μM (α-glucosidase). The obtained results were compared to those of the standard acarbose drug (IC50 = 10.30 ± 0.20 μM for α-amylase and IC50 = 9.80 ± 0.20 μM for α-glucosidase). Specifically, compounds 17, 15, and 16 were found to be significantly active with IC50 values of 0.70 ± 0.05, 1.80 ± 0.10, and 2.10 ± 0.10 μM against α-amylase and 1.10 ± 0.05, 1.50 ± 0.05, and 1.70 ± 0.10 μM against α-glucosidase, respectively. These findings reveal that triazole-containing bis-hydrazones act as α-amylase and α-glucosidase inhibitors, which help develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic agents.

Dataset Information

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Publications

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets