Drug Design, Development and Therapy (Oct 2019)
Enzyme Inhibitory, Antioxidant And Antibacterial Potentials Of Synthetic Symmetrical And Unsymmetrical Thioureas
Abstract
Sumaira Naz,1 Muhammad Zahoor,1 Muhammad Naveed Umar,1 Barkat Ali,1,2 Riaz Ullah,3 Abdelaaty A Shahat,3,4 Hafiz Majid Mahmood,5 Muhammad Umar Khayam Sahibzada6 1Department of Chemistry, University of Malakand Chakdara, Dir Lower, Kpk 18800, Pakistan; 2Department of Chemistry, GC University Faisalabad, Faisalabad, Punjab, Pakistan; 3Medicinal, Aromatic and Poisonous Plants Research Center (MAPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 4Phytochemistry Department, National Research Centre, Giza, Egypt; 5Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 6Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Kpk 25000, PakistanCorrespondence: Muhammad Umar Khayam SahibzadaDepartment of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK 25000, PakistanEmail [email protected] ZahoorDepartment of Chemistry, University of Malakand Chakdara, Dir Lower, KPK 18800, PakistanEmail [email protected]: 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
