Enzyme Inhibitory, Antioxidant And Antibacterial Potentials Of Synthetic Symmetrical And Unsymmetrical Thioureas

Abstract

Background

In this study, 2 symmetrical and 3 unsymmetrical thioureas were synthesized to evaluate their antioxidant, antibacterial, antidiabetic, and anticholinesterase potentials.

Methods

The symmetrical thioureas were synthesized in aqueous media in the presence of sunlight, using amines and CS₂ as starting material. The unsymmetrical thioureas were synthesized using amines as a nucleophile to attack the phenyl isothiocyanate (electrophile). The structures of synthesized compounds were confirmed through H¹ NMR. The antioxidant potential was determined using DPPH and ABTS assays. The inhibition of glucose-6-phosphatase, alpha amylase, and alpha glucosidase by synthesized compounds was used as an indication of antidiabetic potential. Anticholinesterase potential was determined from the inhibition of acetylcholinesterase and butyrylcholinesterase by the synthesized compounds.

Results

The highest inhibition of glucose-6-phosphatase was shown by compound V (03.12 mg of phosphate released). Alpha amylase was most potently inhibited by compound IV with IC₅₀ value of 62 µg/mL while alpha glucosidase by compound III with IC₅₀ value of 75 µg/mL. The enzymes, acetylcholinesterase, and butyrylcholinesterase were potently inhibited by compound III with IC₅₀ of 63 µg/mL and 80 µg/mL respectively. Against DPPH free radical, compound IV was more potent (IC₅₀ = 64 µg/mL) while ABTS was more potently scavenged by compound I with IC₅₀ of 66 µg/mL. The antibacterial spectrum of synthesized compounds was determined against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Agrobacterium tumefaction and Proteus vulgaris). Compound I and compound II showed maximum activity against A. tumefaction with MIC values of 4.02 and 4.04 µg/mL respectively. Against P. vulgaris, compound V was more active (MIC = 8.94 µg/mL) while against S. aureus, compound IV was more potent with MIC of 4.03 µg/mL.

Conclusion

From the results, it was concluded that these compounds could be used as antibacterial, antioxidant, and antidiabetic agents. However, further in vivo studies are needed to determine the toxicological effect of these compounds in living bodies. The compounds also have potential to treat neurodegenerative diseases.

Keywords:

• picolylamine
• symmetrical thioureas
• enzyme inhibition
• anti-diabetic
• antioxidant
• Alzheimer’s disease
• antibacterial

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group no RG-1440-100.

Availability Of Data And Material

The data in the form of the thesis will be provided on demand.

Author Contributions

S.N. and M.Z. conceived and designed the experiments; M.N.U., B.A., R.U. and M.U.K.S. performed the experiments; M.Z., A.A.S and H.M.M. analyzed the data; M.Z., and M.U.K.S contributed reagents and materials. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.