Design, Synthesis and Antidiabetic Activity of Biphenylcarbonitrile‐Thiazolidinedione Conjugates as Potential α‐Amylase Inhibitors. Issue 9 (4th March 2021)

• Record Type: Journal Article
• Authors: Rathod, Chirag H.; Nariya, Pankajkumar B.; Maliwal, Deepika; Pissurlenkar, Raghuvir R. S.; Kapuriya, Naval P.; Patel, Anilkumar S.
• Is Part Of: ChemistrySelect. Volume 6:Issue 9(2021)
• Page Start: 2464
• Page End: 2469
• Publication Date: 2021-03-04
• Subjects: α-amylase inhibitor -- antidiabetic activity -- molecular docking -- 2, 4-thiazolidinedione -- Type 2 Diabetes mellitus; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202004362
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: The α‐amylase inhibition has been considered as an effective therapeutic approach against chronic Type 2 Diabetes mellitus (DM). In the present study, a series of biphenylcarbonitrile‐thiazolidinedione conjugates have been synthesized and evaluated for their antidiabetic activity via α‐amylase inhibition. It was found that most of the conjugates (14 a –j ) exhibited significant α‐amylase inhibition activity compared to the standard drug Acarbose. Off these, compound 14 b, 14 c and 14 d were most potent with IC50 value 0.13 μM, 0.15 μM and 0.13 μM respectively. To ascertain ligand‐receptor interactions, the in silico molecular docking studies of these conjugates (14 a –j ) have been carried out into the Acarbose active site of barley (malt) α‐amylase enzyme. The results have shown fair corroboration between significant α‐amylase inhibition activity of 14 b, 14 c and 14 d and their docking scores compared to the standard drug Acarbose. This study demonstrated that biphenylcarbonitrile‐thiazolidinedione conjugate could be a plausible pharmacophore for targeting α‐amylase for the treatment of Type 2 Diabetes mellitus. Abstract : A series of biphenylcarbonitrile‐thiazolidinedione conjugates have been designed and synthesized. A molecular docking study and an investigation of the antidiabetic activity through α‐amylase inhibition were performed. It was found that most of the syntheized conjugates showed significant α‐amylase inhibition activity compared to the standard drug Acarbose. This study provided an important contemplation about scaffold combination for targeting α‐amylase.