Synthesis and biological evaluation of a new series of benzofuran‐1,3,4‐oxadiazole containing 1,2,3‐triazole‐acetamides as potential α‐glucosidase inhibitors (original) (raw)
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Archiv der Pharmazie, 2019
A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising
Anticoagulant evaluation of 1,3,4-oxadiazole derivatives derived from benzimidazole
In the present study, a series of 1,3,4-oxadiazole derivatives (4a-4k) derived from benzimidazole were evaluated for ex vivo anticoagulant activity. The anticoagulant study was performed for increase in prothrombin time (PT) and activated partial thromboplastin time (aPTT) at a test dose of 25 mg kg-1. The results of ex vivo anticoagulant evaluation revealed that the tested compounds 4a-4k exhibited moderate increase in PT with respect to acenocoumarol (1 mg kg-1) employed as reference drug for increase in PT. While the compounds 4a-4k exhibited minimal increase in aPTT in comparison to unfractionated heparin (500 IU kg-1) employed as reference drug for increase in aPTT. Compounds, 4c, 4b and 4k exhibited substantial anticoagulant activity with increase in PT 32 ± 0.7, 36 ± 0.5 and 41 ± 0.4 s, respectively to that of the reference drug acenocoumarol (48 ± 0.5 s).
EX VIVO ANTICOAGULANT ACTIVITY OF 1, 3, 4-OXADIAZOLE DERIVATIVES
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Objective: The present medication for the management of arterial thromboembolism (ATE) disorders by anticoagulant therapy highlights its lacunae due to recurrent ATE episodes and indicates the need for better anticoagulant agents with clinical advantage. Methods: The anticoagulant study was performed for increase in prothrombin time (PT) and activated partial thromboplastin time (aPTT) at a test dose of 25 mg kg-1 Results: The results of ex vivo anticoagulant evaluation revealed that the tested compounds 3a-3q did not exhibit a significant increase in PT with respect to acenocoumarol (1 mg kg .-1) employed as the reference drug for increase in PT. While the compounds, 3a-3q exhibited minimal increase in aPTT in comparison to unfractionated heparin (500 IU kg-1 Conclusion: The anticoagulant efficacy investigation highlights that the synthesized compound 3q could be considered for further clinical studies to ascertain its possible hit as anticoagulant agents.) employed as the reference drug for increase in aPTT. Among all the tested compounds, only compound 3q exhibited moderate anticoagulant activity with an increase in PT (33 ± 0.4 s) to that of the reference drug acenocoumarol (48 ± 0.5 s).
ACS Omega
The current study evaluates antidiabetic, anticoagulant, and antiplatelet activity of novel benzimidazole-containing quinolinyl oxadiazoles. These derivatives are synthesized and characterized using spectroscopy (FT-IR, 1 H NMR, and mass spectroscopy) and singlecrystal X-ray diffraction methods. The inhibitory effects of these compounds were evaluated by the α-glucosidase inhibitory assay and shows the activity in the range of IC 50 = 0.66 ± 0.05 to 3.79 ± 0.46 μg/mL. In addition, molecular docking studies revealed that benzimidazole-containing quinolinyl oxadiazoles can correctly dock into the target receptor protein of the human intestinal α-glucosidase, while their bioavailability/drug-likeness was predicted to be acceptable but requires further optimization. On the other hand, compound 8a and 8d showed anticoagulant activity as they enhanced the clotting time from control 180−410 and 180−390 s, respectively, in platelet rich plasma and 230−460 and 230−545 s in platelet poor plasma. Furthermore, only 8a showed antiplatelet activity by inhibiting epinephrine-induced platelet aggregation, and the observed aggregation inhibition was found to be 93.4%. Compounds 8a−f show nontoxic properties because of the non-hydrolyzing properties in the RBC cells. In addition, 8a and 8d show anti-edema and anti-hemorrhagic properties in the experimental mice. These findings reveal that benzimidazolecontaining quinolinyl oxadiazoles act as α-glucosidase inhibitors to develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic and antithrombotic agents.
Pakistan journal of pharmaceutical sciences, 2019
A series of 1, 2, 4-triazole derivatives bearing piperidine moiety has been introduced as new anti-diabetic drug candidates with least cytotoxicity. p-Chlorophenylsulfonyl chloride (1) and ethyl nipecotate (2) were the starting reagents that resulted into corresponding 3,4,5-trisubstituted-1,2,4-triazole (6) through a series of steps. A series of electrophiles, 9a-e, were synthesized by reacting 4-bromobutyryl chloride (7) with differently substituted aromatic amines (8a-e) under basic aqueous medium. Target derivatives, 10a-e, were synthesized by the reaction of compound 6 with N-aryl-4-bromobutanamides (9a-e) in an aprotic solvent. Structures of all the derivatives were verified by spectroscopic analysis using IR, 1H-NMR, 13C-NMR and EIMS. Most of the derivatives revealed moderate to good α-glucosidase inhibitory activity with reference to acarbose. The moderate hemolytic potential demonstrated least toxicity.
Oxindole based oxadiazole hybrid analogs: Novel α-glucosidase inhibitors
Bioorganic chemistry, 2017
Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. Beside these α-glucosidase inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in view the greater importance of α-glucosidase inhibitors here in this study we are presenting oxindole based oxadiazoles hybrid analogs (1-20) synthesis, characterized by different spectroscopic techniques including 1H NMR and EI-MS and their α-glucosidase inhibitory activity. All compounds were found potent inhibitors for the enzyme with IC50 values ranging between 1.25 ± 0.05 and 268.36 ± 4.22 µM when compared with the standard drug acarbose having IC50 value 895.09 ± 2.04 µM. Our study identifies novel series of potent α-glucosidase inhibitors and further investigation on this may led to the lead compounds. A structure activity relationship has been established for all compounds. The interactions of the active compounds and enzyme active site were established ...
Bioorganic chemistry, 2016
Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction.
Bioorganic & Medicinal Chemistry, 2019
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Synthesis and Antiplatelet Potential Evaluation of 1,3,4-Oxadiazoles Derivatives
Zeitschrift für Physikalische Chemie, 2019
A novel series of 2-(3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-5-aryl-1,3,4-oxadiazoles (4a–4h) has been synthesized from corresponding hydrazones (3a–3h) and evaluated their antiplatelet aggregation effect induced by arachidonic acid and collagen. Spectral data and elemental evaluation were used to confirm the structure of the compounds while molecular docking against cyclooxygenase 1 and 2 (COX1 & COX2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential. All synthesized compound exhibited more than 50% platelet aggregation inhibition against both arachidonic acid and collagen. Antiplatelet activities results showed that 4b and 4f compounds have highest % inhibition against arachidonic acid. High Egap and ionization potential values showed that the compound 4d, 4e and 4f were supposed to be more active and good electron donor while 4b, 4c, 4d, 4e, 4g and 4h might be more active due to more electrophilic site...