PPAR gamma targeted molecular docking and synthesis of some new amide and urea substituted 1, 3, 4‐thiadiazole derivative as antidiabetic compound

Abstract

The PPAR‐γ agonist enhances the insulin sensitivity and avoids the disorganized hyperglycemic by promoting the insulin guided cellular uptake of blood glucose. Therefore, in the present work PPAR‐γ has chosen as the target for the molecular docking study to design an effective agonist of the same. By this research work an effort has been made to prepare amide and urea series of 1, 3, 4‐thiadiazole derivatives as 4‐substituted‐N‐(5‐(4‐(1‐piperidino)1‐piperidinyl)‐1,3,4‐(2‐thiadiazolyl)benzamide (4a‐f) and 1‐(4‐substitutedphenyl)‐3‐(5‐(4‐(1‐piperidino)1‐piperidinyl)‐1,3,4‐(2‐thiadiazolyl)urea (6a‐f). Both the docking score as well as the pharmacological animal study data has been suggested that the electron donating group containing compound 4f and 6f are most potent molecules for the antidiabetic activity close to the standard drug pioglitazone. It was further observed that the unsubstituted aromatic ring containing derivatives have also considerable effect (4a and 6a) than the electron withdrawing containing derivatives. After the comparison of biological data for amide and urea series, it was concluded that the urea (6a‐f) series is more effective than the amide series.

Synthesis, crystal structure and evaluation of anticancer activities of some novel heterocyclic compounds based on thymol

“…antimicrobial [31][32][33], antidiabetic [34][35][36], antitubercular, [37][38], antiviral [39][40] and anticancer activities [41][42][43]. For example, [N-(4-acetyl-4,5-dihydro-5-methyl-5-phenyl-1,3,4thiadiazol-2-yl)acetamide] (D in Fig.…”

Recent Studies of Nitrogen and Sulfur Containing Heterocyclic Analogues as Novel Antidiabetic Agents: A Review

“…demonstrated molecular docking with PPAR‐γ targeting and the synthesis of several novel 1,3,4‐thiadiazole compounds with amide and urea substitution as antidiabetic agents. Compounds 73 and 74 containing the electron donating methyl substituted aromatic group exhibited potent PPAR‐γ % inhibition with 87.5 % and 89.7 % rise in Blood glucose levels and Target proteins and synthetic derivatives are actively involved in binding, according to a molecular docking study, and there is a strong connection between these results with biological activity [85] . Hameed SA et al.…”

“…Compounds 73 and 74 containing the electron donating methyl substituted aromatic group exhibited potent PPAR-γ % inhibition with 87.5 % and 89.7 % rise in Blood glucose levels and Target proteins and synthetic derivatives are actively involved in binding, according to a molecular docking study, and there is a strong connection between these results with biological activity. [85] Hameed SA et al investigated a number of new derivatives of 5-furyl-1,3,4-thiadiazol-2-imine, designing and synthesizing those with favourable physiochemical properties and further screened for α-amylase activity. Compound 75 exhibited potent % inhibitory activity with 94.55 � 1.80 % as compared to standard acarbose 93.58 % inhibition and formed H-bonds with Ala198, His201, Ala198 with α-amylase binding pocket.…”

Design, synthesis, spectroscopic characterization, computational analysis, and in vitro α-amylase and α-glucosidase evaluation of 3-aminopyridin-2(1H)-one based novel monothiooxamides and 1,3,4-thiadiazoles

“…44 These data are also confirmed in numerous other works. [45][46][47][48] For example, Parvesh Singh 48 reported on the synthesis of new 1,3,4-thiadiazole derivatives, among which a compound (Fig. 3, compound C) was identified that showed a high degree of inhibition of α-glucosidase and α-amylase with an IC value of 2.59 μM, which is ∼1.5 and 14 times higher than that of the standard inhibitor acarbose.…”