Exploring The Therapeutic Potential Of Benzimidazole-Diethylenediamine, Hexahydro-Pyrazine, 1,4-Diazacyclohexane Conjugates: A Synthetic Approach Towards The Development Of Antidiabetic And Antioxidant Agents

Abstract

A new 6-(4-substitue-piperazin-1-yl)-2-aryl-1H-benzimidazole derivatives were designed and expeditiously synthesized starting from 5-(4-phenylpiperazin-1-yl)-2- nitroaniline or 5-(4-ethylpiperazin-1-yl)-2-nitroaniline with different aldehydes. The piperazine ring was located at the C-6 of the successfully synthesized benzimidazole derivatives. Conventionally, this kind of reaction occurs with two steps: reduction and cyclization. This study's quick "one-pot" nitro reductive cyclization reaction employing sodium dithionite as a reagent made the synthetic technique efficient. The potential for both antioxidant and antidiabetic effects was investigated in all synthesized new substances. The newly synthesized compounds showed α-glucosidase inhibitory potential between IC₅₀ = 0.85 ± 0.25 - 29.72 ± 0.17 µM and α-amylase inhibition potential between IC₅₀ = 4.75 ± 0.24 - 40.24 ± 0.10 µM. Among the investigated compounds, 1f demonstrated the most substantial α-glucosidase and α-amylase inhibitory activities, with an IC₅₀ value of 0.85 ± 0.25 µM, 4.75 ± 0.24 µM, respectively. According to the analysis of the kinetic experiments, these chemicals inhibit a competitive mechanism. Additionally, molecular docking experiments revealed the interaction profile of each drug when assessing their dock scores to obtain insight into how each chemical would bind to the α-glucosidase and α-amylase enzymes.