Novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine derivatives embedded with benzimidazole moiety as potent antioxidants

Abstract

Fourteen novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine derivatives bearing benzimidazole moiety (7a‐n) have been synthesized using the one‐pot nitro reductive cyclization method. All the synthesized compounds were confirmed by 1H nuclear magnetic resonance (1H NMR), 13C NMR, fourier‐transform infrared (FT‐IR), mass spectrum, and elemental analyses. All the title compounds were subjected to in vitro antioxidant activity. The free radical scavenging activity of the compounds was examined using DPPH, nitric oxide, and superoxide radical scavenging methods. The results demonstrated that compound 3‐(2‐(3,4‐dimethoxyphenyl)‐1‐propyl‐1H‐benzo[d]imidazol‐5‐yl)‐6‐4‐tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine (7c) was potent in scavenging both DPPH and nitric oxide radical with IC50 values of 13.57 and 18.55 μg/ml when compared to the standard with IC50 values of 23.75 and 23.14 μg/ml, respectively, which was due to the presence of electron‐donating groups. The activity was found to decline when electron‐donating groups were replaced by electron‐withdrawing groups. Moderate scavenging activity was observed for the superoxide radical. Structure activity relationship and physiochemical properties were studied for all the derivatives.

Vision on Synthetic and Medicinal Facets of 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazine Scaffold

“…Sathyanarayana et al [ 113 ] designed and synthesized benzimidazole linked 1,2,4-triazolo[3,4- b ][1,3,4]thiadiazine derivatives ( 146 ) and assessed their in vitro antioxidant potential using DPPH, nitric oxide and superoxide radical scavenging methods. Among them, compound 146c showed more activity in both DPPH and nitric oxide radical assay, with IC 50 values of 13.57 and 18.55 μg ml −1 compared with standard (IC 50 = 23.75 and 23.14 μg ml −1 , respectively).…”

“…Sathyanarayana et al [ 113 ] reported that novel [1,2,4]triazolo[3,4- b ][1,3,4]thiadiazine derivatives 146 bearing benzimidazole moiety obeyed most of the ADME parameters. Most of these compounds showed TPSA < 80 Å 2 , indicating their good intestinal absorption.…”

Discovery of 2‐Amino‐4H‐1, 3, 4‐thiadiazine‐5(6H)‐one Derivatives and Their In Vitro Antitumor Investigation

“…Meanwhile, thiadiazine‐based compounds have attracted significant interest as shown in Figure 1, due to their wide‐applicability as biologically active compounds [6,7] . Their moiety was reported to exhibit anticancer, anti‐coronavirus, [8] anti‐bacterial, [9] anti‐HIV, [10] and antioxidant activities [11] …”