In vitro inhibitor effect and molecular docking of thiamine (vitamin B₁), riboflavin (vitamin B₂), and reference inhibitor captopril on angiotensin-converting enzyme purified from sheep plasma

Abstract

Objective

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a very important factor in the regulation of blood pressure. Also, the inhibition of ACE with natural compounds has been a very important research area in the treatment of high blood pressure. ACE was purified and characterized from sheep plasma. Molecular docking studies and the inhibition effect of thiamine, riboflavin, and captopril on ACE were investigated.

Methods

Herein, ACE was purified from sheep plasma by affinity chromatography. The effect of thiamine and riboflavin on ACE was researched. Molecular docking studies were performed to understand the molecular interactions between thiamine, riboflavin, and captopril with ACE.

Results

The purification coefficient was found to be 8636 fold. The binding energy of thiamine, riboflavin, and captopril was found to be -6.7 kcal/mol, -8.1 kcal/mol, and -5.5 kcal/mol, respectively. Thiamine conformed to three conventional hydrogen bonds with ASP:415, HIS:513, and LYS:454. Riboflavin formed four conventional hydrogen bonds with GLN:281, GLU:376, THR:282, and TYR:520. Captopril formed two conventional hydrogen bonds with ARG:124, one conventional hydrogen bond with TYR:62 and ASN:85, and one carbon-hydrogen bond with ASN:66. Molecular docking results showed that thiamine, riboflavin, and captopril interacted with ACE through hydrogen bonding and hydrophobic interactions. Thiamine and riboflavin indicated significant inhibition effects on ACE. The IC₅₀ values of thiamine, riboflavin, and captopril were found as 960.56 µM, 11.02 µM, and 1.60 nM, respectively. K_i values for thiamine, riboflavin, and captopril were determined as 1352.04 µM, 12.30 µM, and 1.06 nM, respectively.

Conclusion

In this work, it was concluded that thiamine and riboflavin may have preventive and therapeutical impacts against high blood pressure with their ACE inhibitor effect. Thiamine and riboflavin showed a lower inhibitory effect with a higher IC₅₀ than captopril. However, when the inhibitory effect of thiamine and riboflavin vitamins is compared to captopril, it is concluded that they may be natural inhibitors with fewer side effects.

Keywords:

• Angiotensin-converting enzyme
• inhibition
• purification
• riboflavin
• thiamine

Ethical approval

This work involved the chemical analyses of animal sources. No approval of animal use protocols was required.

Author contributions

V.T.: Supervision, Conceptualisation, and Project Administration. V.T., M.H.C., Z.B., and F.C.C.: Data curation, Writing-original draft preparation. M.H.C., V.T., Z.B., and F.C.C.: Performed the experiments. V.T. and Z.B.: Visualisation, Investigation, Writing-review & editing.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work ­featured in this article.