New ferrocene integrated amphiphilic guanidines: Synthesis, spectroscopic elucidation, DFT calculation and in vitro α-amylase and α-glucosidase inhibition combined with molecular docking approach

新型二茂铁两亲性胍类化合物:合成、光谱表征、DFT计算及体外α-淀粉酶和α-葡萄糖苷酶抑制活性研究,并结合分子对接方法进行分析

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Abstract

Three N, N', N″-trisubstituted ferrocenyl guanidines (MG-10, MG-12 and MG-14) were synthesized, characterized by several analytical methods such as FT-IR, (1)H and (13)C NMR, elemental analysis and UV-visible spectroscopy. These compounds have long chain aliphatic groups therefore their aliphatic nature has been evaluated by determining their critical micelle concentration (CMC). CMC point decreases from 0.036 mM to 0.013 mM with increase in the aliphatic chain length. The quantum mechanical parameters such as the energy of frontier molecular orbitals (E(HOMO) and E(LUMO)) and the Mulliken charge distribution on the optimized structures were determined using a DFT/B3LYP method combined with the 6-31G (d,p) basis set in the gas phase. The in vitro antidiabetic activity of synthesized compounds showed that MG-12 has IC(50)value 23.10 μg/mL against α-amylase while MG-10 has IC(50)value 27.32 μg/mL against α-glucosidase with the respective standard Acarbose (IC(50)value 20.12 μg/mL). Theoretical docking analysis demonstrated that MG-10 and MG-12 interacted with α-amylase by 3 types of interaction, including hydrogen bonds, hydrophobic interactions and electrostatic interactions.

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