Studies on synthesis and bioactivity of some functionalized heterocycles

Abstract

In the projected study have been divided by five different chapter. Apart from this, present work has divided base on the heterocyclic motifs, such as thiazolidine-2,4-one, pyrrole, thiazole and imidazole. newlineThiazolidine-2,4-one newlineThe and#945;-amylase inhibition has been considered as an effective therapeutic approach against chronic type 2 diabetes mellitus (DM). In the present study, a series of biphenyl carbonitrile thiazolidinedione conjugates have been synthesized and evaluated for their antidiabetic activity via and#945;-amylase inhibition. It was found that most of the conjugates (68a-j) exhibited significant and#945;-amylase inhibition activity compared to the standard drug Acarbose. Off these, compound 68b (3-O-Ph), 68c (4-F) and 68d (3,4,5-tri OCH3) were most potent with IC50 value 0.13 and#956;M, 0.15 and#956;M and 0.13 and#956;M respectively. To ascertain ligand-receptor interactions the in silico molecular docking studies of these conjugates (68a-j) have been carried out into the acarbose active site of barley (malt) and#945;-amylase enzyme. The results have shown fair corroboration between significant and#945;-amylase inhibition activity of 68b, 68c and 68d and their docking scores compared to the standard drug acarbose. This study demonstrated that biphenyl carbonitrile-thiazolidinedione conjugate could be a plausible pharmacophore for targeting and#945;-amylase for the treatment of type 2 diabetes mellitus. newlinePyrrole newlineCycloaddition reaction of reissert hydrofluoroborate salt of quinoline/phenanthridine with a-bromoacrylamides has been carried out. Optimized condition has been developed for the [4+2] cycloaddition reaction by using K2CO3 in DMF under moderate temperature for highly functionalized pyrrole derivative (74a-f and 75a-f) in good to excellent yield. The newly synthesized compounds were characterized by IR, Mass, 1H and 13C NMR spectroscopy. In addition, compound 75a has been confirmed by 2D NMR experiments. The results have shown moderate antimicrobial activity.