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Synthesis and studies of thiazolidinedione–isatin hybrids as α-glucosidase inhibitors for management of diabetes

    Ramandeep Kaur

    University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

    ,
    Rajnish Kumar

    Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Varanasi 221005, India

    ,
    Nilambra Dogra

    Centre for Systems Biology & Bioinformatics, Panjab University, Chandigarh 160014, India

    ,
    Ashok Kumar

    Centre for Systems Biology & Bioinformatics, Panjab University, Chandigarh 160014, India

    ,
    Ashok Kumar Yadav

    University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

    &
    Manoj Kumar

    *Author for correspondence: Tel.: +91 941 745 5011;

    E-mail Address: manoj_uips@pu.ac.in

    University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

    Published Online:https://doi.org/10.4155/fmc-2020-0022

    Aim: Keeping in view the side effects associated with clinically used α-glucosidase inhibitors, novel thiazolidinedione–isatin hybrids were synthesized and evaluated by in vitro, in vivo and in silico procedures. Materials & methods: Biological evaluation, cytotoxicity assessment, molecular docking, binding free energy calculations and molecular dynamics studies were performed for hybrids. Results: The most potent inhibitor A-10 (IC50 = 24.73 ± 0.93 μM) was competitive in manner and observed as non-cytotoxic. A-10 possessed higher efficacy than the standard drug (acarbose) during in vivo biological testing. Conclusion: The enzyme inhibitory potential and safety profile of synthetic molecules was recognized after in vitro, in vivo, in silico and cytotoxicity studies. Further structural optimization of A-10 can offer potential hit molecules suitable for future investigations.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest

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