In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone
2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is an important molecule found in Melicope pteleifolia and has been reported to exhibit numerous pharmacological activities including LOX inhibition. As part of our continuing efort to search for new 15-sLOX inhibitor with better in vitro efcacies, a C...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media Deutschland GmbH
2025
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| Online Access: | http://umpir.ump.edu.my/id/eprint/44496/ http://umpir.ump.edu.my/id/eprint/44496/1/In%20vitro%20and%20in%20silico%20insights%20into%20the%20soybean.pdf |
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| author | Segaran, Raaginie Tamil Mohd Fadhlizil Fasihi, Mohd Aluwi Lam, Kok Wai Siti Nur Aisyah, Mohd Hashim Syahrul, Imran Ng, Chean Hui |
| author_facet | Segaran, Raaginie Tamil Mohd Fadhlizil Fasihi, Mohd Aluwi Lam, Kok Wai Siti Nur Aisyah, Mohd Hashim Syahrul, Imran Ng, Chean Hui |
| author_sort | Segaran, Raaginie Tamil |
| building | UMP Institutional Repository |
| collection | Online Access |
| description | 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is an important molecule found in Melicope pteleifolia and has been reported
to exhibit numerous pharmacological activities including LOX inhibition. As part of our continuing efort to search for new
15-sLOX inhibitor with better in vitro efcacies, a C-geranylated chalcone-based favanone (8) was synthesized via facile
Friedel–Crafts acylation followed by direct C-alkylation. The synthesized favanone was assayed for its in-vitro inhibition
against soybean 15-lipoxygenase (15-sLOX); and predicted for its pharmacodynamic and pharmacokinetic properties using
docking simulation, SwissADME and PreADMET server. Results indicated that direct C-alkylation on chalcone intermediate using potassium carbonate as base catalyst was possible to establish the conditions that favor the isomerization of
chalcone into favanone. The synthesized favanone (8) showed better LOX inhibitory activity (IC50: 1.02±0.15 µM) when
compared to our previously reported parent compound tHGA (1, IC50: 23.6±1.7 µM) and its chalcone-based analogue (2,
IC50: 15.2±1.2 µM). The (R) enantiomer of favanone (8) showed a good dock score (−9.97 kcal/mol) which interacts with
the target enzyme through one hydrogen bonding, and one hydrophobic interaction with iron-binding amino acid (His 499).
Molecular dynamics simulation with 100 ns refned and confrmed the docking study result, and the stability of the complex was verifed based on root-mean-square deviation (RMSD), root-mean-square-fuctuation (RMSF), and protein–ligand
interaction analyses. The (R) enantiomer of favanone (8) showed stable hydrophobic and hydrophilic contacts in the active
site. This study provides insights into the 15-sLOX inhibitory profle of a C-geranylated chalcone-based favanone with an
electron withdrawing substituents (-F-) at ring B as potent lead. |
| first_indexed | 2025-11-15T03:55:36Z |
| format | Article |
| id | ump-44496 |
| institution | Universiti Malaysia Pahang |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T03:55:36Z |
| publishDate | 2025 |
| publisher | Springer Science and Business Media Deutschland GmbH |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | ump-444962025-05-05T08:46:33Z http://umpir.ump.edu.my/id/eprint/44496/ In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone Segaran, Raaginie Tamil Mohd Fadhlizil Fasihi, Mohd Aluwi Lam, Kok Wai Siti Nur Aisyah, Mohd Hashim Syahrul, Imran Ng, Chean Hui QD Chemistry QP Physiology RS Pharmacy and materia medica 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is an important molecule found in Melicope pteleifolia and has been reported to exhibit numerous pharmacological activities including LOX inhibition. As part of our continuing efort to search for new 15-sLOX inhibitor with better in vitro efcacies, a C-geranylated chalcone-based favanone (8) was synthesized via facile Friedel–Crafts acylation followed by direct C-alkylation. The synthesized favanone was assayed for its in-vitro inhibition against soybean 15-lipoxygenase (15-sLOX); and predicted for its pharmacodynamic and pharmacokinetic properties using docking simulation, SwissADME and PreADMET server. Results indicated that direct C-alkylation on chalcone intermediate using potassium carbonate as base catalyst was possible to establish the conditions that favor the isomerization of chalcone into favanone. The synthesized favanone (8) showed better LOX inhibitory activity (IC50: 1.02±0.15 µM) when compared to our previously reported parent compound tHGA (1, IC50: 23.6±1.7 µM) and its chalcone-based analogue (2, IC50: 15.2±1.2 µM). The (R) enantiomer of favanone (8) showed a good dock score (−9.97 kcal/mol) which interacts with the target enzyme through one hydrogen bonding, and one hydrophobic interaction with iron-binding amino acid (His 499). Molecular dynamics simulation with 100 ns refned and confrmed the docking study result, and the stability of the complex was verifed based on root-mean-square deviation (RMSD), root-mean-square-fuctuation (RMSF), and protein–ligand interaction analyses. The (R) enantiomer of favanone (8) showed stable hydrophobic and hydrophilic contacts in the active site. This study provides insights into the 15-sLOX inhibitory profle of a C-geranylated chalcone-based favanone with an electron withdrawing substituents (-F-) at ring B as potent lead. Springer Science and Business Media Deutschland GmbH 2025 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/44496/1/In%20vitro%20and%20in%20silico%20insights%20into%20the%20soybean.pdf Segaran, Raaginie Tamil and Mohd Fadhlizil Fasihi, Mohd Aluwi and Lam, Kok Wai and Siti Nur Aisyah, Mohd Hashim and Syahrul, Imran and Ng, Chean Hui (2025) In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone. Chemical Papers, 79 (1). pp. 583-591. ISSN 0366-6352. (Published) https://doi.org/10.1007/s11696-024-03820-9 https://doi.org/10.1007/s11696-024-03820-9 |
| spellingShingle | QD Chemistry QP Physiology RS Pharmacy and materia medica Segaran, Raaginie Tamil Mohd Fadhlizil Fasihi, Mohd Aluwi Lam, Kok Wai Siti Nur Aisyah, Mohd Hashim Syahrul, Imran Ng, Chean Hui In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title | In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title_full | In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title_fullStr | In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title_full_unstemmed | In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title_short | In vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new C-geranylated chalcone-based flavanone |
| title_sort | in vitro and in silico insights into the soybean 15-lipoxygenase inhibition with a new c-geranylated chalcone-based flavanone |
| topic | QD Chemistry QP Physiology RS Pharmacy and materia medica |
| url | http://umpir.ump.edu.my/id/eprint/44496/ http://umpir.ump.edu.my/id/eprint/44496/ http://umpir.ump.edu.my/id/eprint/44496/ http://umpir.ump.edu.my/id/eprint/44496/1/In%20vitro%20and%20in%20silico%20insights%20into%20the%20soybean.pdf |