Construction of fatty acid derivatives from rubber seed oil as α-glucosidase inhibitors based on rubber seed oil

Abstract

Natural free fatty acids show inhibitory effects on α-glucosidase and can hence have potential applications in diabetes treatment. This study indicated that the inhibitory effect of fatty acids showed a significant negative correlation with affinity energy (− 0.87) and melting point (− 0.88). Guided by this relationship, two promotion strategies of hydration and esterification were put forward to increase the inhibitory effect of fatty acids on α-glucosidase. The hydration can import an extra hydroxy group into the C=C bond of fatty acids, that will enhance the interaction with α-glucosidase, while the esterification will lower the melting point of fatty acids, and promote the inhibitory effect. Hydroxy fatty acids and fatty acid isopropyl esters possessed higher inhibitory effects than the natural fatty acids. Then, rubber seed oil was modified into novel fatty acid derivatives with higher inhibitory effect on α-glucosidase. The inhibitory IC50 of hydroxy products and isopropanol esters was 0.42 ± 0.01 μM and 0.57 ± 0.01 μM, respectively. The result reveals a feasible route to construct fatty acid derivatives from natural oil with α-glucosidase inhibitory effect. Graphical Abstract

A Comparative Study of Chemical Profiling and Bioactivities between Thai and Foreign Hemp Seed Species (Cannabis sativa L.) Plus an In-Silico Investigation

“…The summarized torsional free energy of all fatty acid esters exhibited a higher value than free fatty acid, indicating less stability (weaker interaction and inhibitory activity). This matched a previous report [ 30 ]. Then, we further evaluated the torsional free energy of each fatty acid according to carbon length and degree of unsaturation, as presented in Figure 3 B.…”

“…The summarized torsional free energy of all fatty acid esters exhibited a higher value than free fatty acid, indicating less stability (weaker interaction and inhibitory activity). This matched a previous report [30].…”

“…The first is torsional free energy, and the second is final total internal energy. Both energies exhibited a vital role in fatty acid and its ester analysis earlier and were related to previously reported experimental data [30]. However, both values were in contradiction.…”

“…To the authors' best knowledge, this is the first study to demonstrate a relationship between a modeled re-scoring docking function and actual experimental data for a series of free fatty acids. Later, we evaluated a relationship between all re-scoring docking functions (1 to 5, as mentioned in the previous paragraph) of all fatty acids found in the current study and previous experimental data based on the aliphatic length and degree of unsaturation [30]. Interestingly, only the final total internal energy correlated to the previous experimental data, while the others did not.…”

“…Later, we evaluated a relationship between all re-scoring docking functions (1 to 5, as mentioned in the previous paragraph) of all fatty acids found in the current study and previous experimental data based on the aliphatic length and degree of unsaturation [30]. Figure 3A demonstrates a re-scoring docking function in each category, starting from the final intermolecular energy (1), the final total internal energy (2), the torsional free energy (3), the unbound system's energy (4), and the estimated free energy of binding (5) of the summarized re-scoring function of five fatty acids and their esters.…”