Synthesis of 2-{[5-(aralkyl/aryl)-1,3,4-oxadiazol-2-yl]sulfanyl}-N-(4-methyl-1,3-thiazol-2-yl)acetamides: Novel bi-heterocycles as potential therapeutic agents

• Main Authors: Abbasi, M.A (Author), Ashraf, M. (Author), Aziz-Ur-Rehman (Author), Khan, F.A (Author), Lodhi, M.A (Author), Mirza, B. (Author), Ramzan, M.S (Author), Shah, S.A.A (Author), Siddiqui, S.Z (Author)
• Format: Article
• Language: English
• Published: University of Benin 2018
• Subjects: 2 [(5 (aralkyl/aryl1,3,4 oxadiazol 2 yl)sulfanyl] n (4 methyl 1,3 thiazol 2 yl) acetamide; 2 [(5 benzyl 1,3,4 oxadiazol 2 yl)sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (2 chloro 3,5 dinitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (2 chlorophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (2 methoxyphenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (2 methyl 3,5 dinitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (2,4 dichlorophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (3 aminophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (3 chlorophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (3,5 dinitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (4 aminophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (4 chlorophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (4 hydroxyphenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 2 [[5 (4 methylphenyl) 1,3,4 oxadiazol 2 yl]sulfanyl] n (4 methyl 1,3 thiazol 2 yl)acetamide; 4-Methyl-1,3-thiazol-2-amine,1,3,4-Oxadiazole; acarbose; alpha glucosidase; Alzheimer disease; Article; bioassay; Brine shrimp; carboxylic acid; cholinesterase inhibition; Cholinesterases; controlled study; cytotoxicity assay; diabetes mellitus; doxorubicin; drug design; drug development; drug synthesis; electron impact mass spectrometry; enzyme inhibition assay; heterocyclic compound; IC50; infrared radiation; molecular docking; n (4 methyl 1,3 thiazol 2 yl) 2 [(5 phenyl 1,3,4 oxadiazol 2 yl)sulfanyl]acetamide; n (4 methyl 1,3 thiazol 2 yl) 2 [[5 (2 nitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl]acetamide; n (4 methyl 1,3 thiazol 2 yl) 2 [[5 (3 nitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl]acetamide; n (4 methyl 1,3 thiazol 2 yl) 2 [[5 (4 nitrophenyl) 1,3,4 oxadiazol 2 yl]sulfanyl]acetamide; n (4 methyl 1,3 thiazol 2 yl) 2 [[5 (naphthalen 1 ylmethyl) 1,3,4 oxadiazol 2 yl]sulfanyl]acetamide; physostigmine; proton nuclear magnetic resonance; thiourea; unclassified drug; Urease; urease inhibitor; α-Glucosidase
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 15965996 (ISSN)
• DOI: 10.4314/tjpr.v17i5.23

Purpose: To evaluate the therapeutic potential of new bi-heterocycles containing a 1,3-thiazole and 1,3,4-oxadiazole in the skeleton against Alzheimer's disease and diabetes, supported by in-silico study. Methods: The synthesis was initiated by the reaction of 4-methyl-1,3-thiazol-2-amine (1) with bromoacetyl bromide (2) in aqueous basic medium to obtain an electrophile,2-bromo-N-(4-methyl-1,3-thiazol-2-yl)acetamide (3). In parallel reactions, a series of carboxylic acids, 4a-r, were converted through a sequence of three steps, into respective 1,3,4-oxadiazole heterocyclic cores, 7a-r, to utilize as nucleophiles. Finally, the designed molecules, 8a-r, were synthesized by coupling 7a-r individually with 3 in an aprotic polar solvent. The structures of these bi-heterocycles were elucidated by infrared (IR), electron ionization-mass spectrometry (EI-MS), proton nuclear magnetic resonance (1H-NMR) and carbon nuclear magnetic resonance (13C-NMR). To evaluate their enzyme inhibitory potential, 8a-r were screened against acetylcholinesterase (AChE), but brine shrimp lethality bioassay. Results: The most active compound against AChE was 8l with half-maximal inhibitory concentration (IC50) of 17.25 ± 0.07 µM. Against BChE, the highest inhibitory effect was shown by 8k (56.23 ± 0.09 µM). Compound 8f (161.26 ± 0.23μM) was recognized as a fairly good inhibitor of urease. In view of its inhibition of α-glucosidase, 8o (57.35 ± 0.17μM) was considered a potential therapeutic agent. Conclusion: The results indicate that some of the synthesized products with low toxicity exhibit notable enzyme inhibitory activity against selected enzymes compared with the reference drug, and therefore, are of potential therapeutic interest. © 2018 The authors.