Mehran Ghasemi, Aida Iraji, Maryam Dehghan, Yazdanbakhsh Lotfi Nosood, Cambyz Irajie, Nafiseh Bagherian Khouzani, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Mohammad Mahdavi, Ahmed Al-Harrasi
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Rational design of new quinoline-benzimidazole scaffold bearing piperazine acetamide derivatives as antidiabetic agents.
In this study, a series of fifteen compounds (7a-o) based on a quinoline-benzimidazole scaffold bearing piperazine acetamide derivatives were synthesized and evaluated for their potential as α-glucosidase inhibitors, which are important therapeutic agents in the management of type 2 diabetes mellitus. Among the synthesized compounds, 7m exhibited the most potent inhibitory activity, demonstrating a 28-fold greater efficacy than the standard clinical inhibitor, acarbose. Molecular docking studies indicated strong binding interactions between 7m and the α-glucosidase active site, including hydrogen bonding, π-π stacking, and π-cation interactions. Furthermore, molecular dynamics simulations revealed that compound 7m formed a highly stable complex with the enzyme. These findings suggest that compound 7m is a promising candidate for further development as an effective antidiabetic agent, offering valuable insights into the design of potent α-glucosidase inhibitors based on the quinoline-benzimidazole framework.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.