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

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).

Khalid et al Chemistry Central Journal (2018) 12:11 https://doi.org/10.1186/s13065-018-0378-5 Open Access RESEARCH ARTICLE Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives Waseem Khalid1, Amir Badshah1, Arif‑ullah Khan1*, Humaira Nadeem1 and Sagheer Ahmed2 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 com‑ pounds 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