Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent
Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English English |
| Published: |
Elsevier B.V.
2024
|
| Subjects: | |
| Online Access: | http://umpir.ump.edu.my/id/eprint/39980/1/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe.pdf http://umpir.ump.edu.my/id/eprint/39980/2/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe%20inhibitor%20of%20mushroom%20tyrosinase%20and%20antibrowning%20agent_ABS.pdf |
| _version_ | 1796996161485144064 |
|---|---|
| author | Nur Amanina, Hassanuddin Erna, Normaya Hakimah, Ismail Anwar, Iqbal Mohd Bijarimi, Mat Piah Shafida, Abd Hamid Mohammad Norazmi, Ahmad |
| author_facet | Nur Amanina, Hassanuddin Erna, Normaya Hakimah, Ismail Anwar, Iqbal Mohd Bijarimi, Mat Piah Shafida, Abd Hamid Mohammad Norazmi, Ahmad |
| author_sort | Nur Amanina, Hassanuddin |
| collection | UMP |
| description | Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS elemental analysis, and proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The vibrational frequencies of 4-PT were studied theoretically using vibrational energy distribution analysis (VEDA). Density functional theory (DFT) was applied to elucidate its chemical properties, including the Mulliken atomic charges, molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM) and reduced density gradient non-covalent interactions (RDG-NCIs). Moreover, 4-PT was compared with kojic acid in terms of its effectiveness as a tyrosinase inhibitor and anti-browning agent. The toxicity and physicochemical properties of 4-PT were predicted via ADME evaluation, which proved that 4-PT is safer than kojic acid. Experimentally, 4-PT (IC50 = 5.82 μM, browning index (10 days) = 0.292 ± 0.002) was proven to be an effective tyrosinase inhibitor and anti-browning agent compared to kojic acid (IC50 = 128.17 μM, browning index (10 days) = 0.332 ± 0.002). Furthermore, kinetic analyses indicated that the type of tyrosinase inhibition is a mixed inhibition, with Km and Vmax values of 0.85 mM and 2.78 E-09 μM/s, respectively. Finally, the mechanism of 4-PT for tyrosinase inhibition was proven by 1D, second derivative and 2D IR spectroscopy, molecular docking and molecular dynamic simulation approaches. |
| first_indexed | 2024-03-06T13:12:53Z |
| format | Article |
| id | UMPir39980 |
| institution | Universiti Malaysia Pahang |
| language | English English |
| last_indexed | 2024-03-06T13:12:53Z |
| publishDate | 2024 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | UMPir399802024-01-12T02:05:36Z http://umpir.ump.edu.my/id/eprint/39980/ Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent Nur Amanina, Hassanuddin Erna, Normaya Hakimah, Ismail Anwar, Iqbal Mohd Bijarimi, Mat Piah Shafida, Abd Hamid Mohammad Norazmi, Ahmad QD Chemistry T Technology (General) TA Engineering (General). Civil engineering (General) TP Chemical technology Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS elemental analysis, and proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The vibrational frequencies of 4-PT were studied theoretically using vibrational energy distribution analysis (VEDA). Density functional theory (DFT) was applied to elucidate its chemical properties, including the Mulliken atomic charges, molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM) and reduced density gradient non-covalent interactions (RDG-NCIs). Moreover, 4-PT was compared with kojic acid in terms of its effectiveness as a tyrosinase inhibitor and anti-browning agent. The toxicity and physicochemical properties of 4-PT were predicted via ADME evaluation, which proved that 4-PT is safer than kojic acid. Experimentally, 4-PT (IC50 = 5.82 μM, browning index (10 days) = 0.292 ± 0.002) was proven to be an effective tyrosinase inhibitor and anti-browning agent compared to kojic acid (IC50 = 128.17 μM, browning index (10 days) = 0.332 ± 0.002). Furthermore, kinetic analyses indicated that the type of tyrosinase inhibition is a mixed inhibition, with Km and Vmax values of 0.85 mM and 2.78 E-09 μM/s, respectively. Finally, the mechanism of 4-PT for tyrosinase inhibition was proven by 1D, second derivative and 2D IR spectroscopy, molecular docking and molecular dynamic simulation approaches. Elsevier B.V. 2024-01 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/39980/1/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe.pdf pdf en http://umpir.ump.edu.my/id/eprint/39980/2/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe%20inhibitor%20of%20mushroom%20tyrosinase%20and%20antibrowning%20agent_ABS.pdf Nur Amanina, Hassanuddin and Erna, Normaya and Hakimah, Ismail and Anwar, Iqbal and Mohd Bijarimi, Mat Piah and Shafida, Abd Hamid and Mohammad Norazmi, Ahmad (2024) Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent. International Journal of Biological Macromolecules, 255 (128229). pp. 1-16. ISSN 0141-8130. (Published) https://doi.org/10.1016/j.ijbiomac.2023.128229 https://doi.org/10.1016/j.ijbiomac.2023.128229 |
| spellingShingle | QD Chemistry T Technology (General) TA Engineering (General). Civil engineering (General) TP Chemical technology Nur Amanina, Hassanuddin Erna, Normaya Hakimah, Ismail Anwar, Iqbal Mohd Bijarimi, Mat Piah Shafida, Abd Hamid Mohammad Norazmi, Ahmad Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title | Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title_full | Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title_fullStr | Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title_full_unstemmed | Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title_short | Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| title_sort | methyl 4 pyridyl ketone thiosemicarbazone 4 pt as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent |
| topic | QD Chemistry T Technology (General) TA Engineering (General). Civil engineering (General) TP Chemical technology |
| url | http://umpir.ump.edu.my/id/eprint/39980/1/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe.pdf http://umpir.ump.edu.my/id/eprint/39980/2/Methyl%204-pyridyl%20ketone%20thiosemicarbazone%20%284-PT%29%20as%20an%20effective%20and%20safe%20inhibitor%20of%20mushroom%20tyrosinase%20and%20antibrowning%20agent_ABS.pdf |
| work_keys_str_mv | AT nuramaninahassanuddin methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT ernanormaya methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT hakimahismail methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT anwariqbal methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT mohdbijarimimatpiah methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT shafidaabdhamid methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent AT mohammadnorazmiahmad methyl4pyridylketonethiosemicarbazone4ptasaneffectiveandsafeinhibitorofmushroomtyrosinaseandantibrowningagent |