A facile Single Pot Synthesis of Highly Functionalized Tricyclic Heterocycle Compounds Via Sequential Knoevenagel-michael Addition and Their ?-glucosidase Inhibition, Antioxidants and Antibacterial Studies. | Journal of Chemical Society of Pakistan 2018

Faiz Ahmed Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; Institute of Chemistry, University of Punjab, Lahore Pakistan; Institute of Chemistry, University of São Paulo, 05508-000 São Paulo, Brazil

Abdul Rauf Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

Ahsan Sharif Institute of Chemistry, University of Punjab, Lahore Pakistan

Ejaz Ahmad Institute of Chemistry, University of Punjab, Lahore Pakistan

Muhammad Arshad Institute of Chemistry, University of Punjab, Lahore Pakistan

Breno Pannia Esposito Institute of Chemistry, University of São Paulo, 05508-000 São Paulo, Brazil

Telma Mary Kaneko Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil

Ashfaq Mahmood Qureshi Department of Chemistry, The Government Sadiq College Women University, Bahawalpur, Pakistan, 63100

Summary: A facile methodology was developed which involved multicomponent single pot reaction which yielded the synthesis of highly functionalized tricyclic-heterocycle compounds (1c6c) 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 (a-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 a-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 µmol/L) as compared to standard acarbose (135.6 µmol/L) making them excellent a-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 µM concentration against 105 CFU/200 µL 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.