A Facile Single Pot Synthesis of Highly Functionalized Tricyclic Heterocycle Compounds via Sequential Knoevenagel-Michael Addition and their alpha-Glucosidase Inhibition, Antioxidants and Antibacterial Studies

作者：Ahmed Faiz; Rauf Abdul^*; Sharif Ahsan; Ahmad Ejaz; Arshad Muhammad; Esposito Breno Pannia; Kaneko Telma Mary; Qureshi Ashfaq Mahmood^*

来源：Journal of the Chemical Society of Pakistan, 2018, 40(4): 761-772.

• Tricyclic Heterocycles
• Sequential Knoevenagel-Michael addition
• alpha-glucosidase inhibition
• Antioxidants
• Antibacterial studies

A facile methodology was developed which involved multicomponent single pot reaction which yielded the synthesis of highly functionalized tricyclic-heterocycle compounds (1c-6c) and (1d-7d) in good yields (60-80%). The discovered novel methodology involved sequential multicomponent reactions; consisting of Knoevenagel reaction followed by Michael addition; moreover, the proposed mechanism is consistent with the stepwise methodology which also availed the same tricyclic heterocycle compounds (1c-6c) and (1d-7d). In-silico (alpha-glucosidase inhibitory studies only) and in-vitro biological evaluation was extensively performed for all the synthesized compounds. Tricyclic-heterocycle compounds (1c-6c) and (1d-7d) showed excellent interacting affinity with receptor protein (PDB ID: 3A47) which were further complemented and confirmed through in-vitro alpha-glucosidase inhibitory studies which were found to be comparable with standard acarbose. Whereas, 3c, 3d and 5d exhibited IC50 value (111.8, 99.4, 108.7 mu mol/L) as compared to standard acarbose (135.6 mu mol/L) making them excellent alpha-glucosidase inhibition candidates among the lot. Furthermore, all the novel synthesized compounds were screened for in-vitro antibacterial, and antioxidant studies, which revealed that all these compounds show mild bacteriostatic properties at 200 mu M concentration against 10 5 CFU/200 mu L, of three bacterial strains; Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, while compounds (2d, 3d, 4d, 6c, 6d) are found more potent antioxidants than the standard ascorbic acid.

• 出版日期2018-8