Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study
Some hydantoin derivatives have been explored for their potential as anticancer agents by inhibiting receptor tyrosine kinases (RTKs). Benzalhydantoin derivatives were obtained from a two-step reaction: condensation and alkylation reaction. The benzalhydantoin activities were obtained from the enzym...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Penerbit Universiti Kebangsaan Malaysia
2025
|
| Online Access: | http://journalarticle.ukm.my/25066/ http://journalarticle.ukm.my/25066/1/SSB%2016.pdf |
| _version_ | 1848816259436642304 |
|---|---|
| author | Muhammad Naufal, Hidayat, Ika Wiani Hermawati, Elvira Syah, Yana Maolana Al-Anshori, Jamaludin |
| author_facet | Muhammad Naufal, Hidayat, Ika Wiani Hermawati, Elvira Syah, Yana Maolana Al-Anshori, Jamaludin |
| author_sort | Muhammad Naufal, |
| building | UKM Institutional Repository |
| collection | Online Access |
| description | Some hydantoin derivatives have been explored for their potential as anticancer agents by inhibiting receptor tyrosine kinases (RTKs). Benzalhydantoin derivatives were obtained from a two-step reaction: condensation and alkylation reaction. The benzalhydantoin activities were obtained from the enzymatic assay, while the molecular interaction was simulated with molecular docking. Five known compounds (5-9) and two new benzalhydantoin derivatives 10-11 have been synthesized from the appropriate precursors with 4-71% yields. The structures of the compounds were determined mainly by NMR and mass spectral data. From the chemical shift of the H-7’, the configuration of the products 5, 7, 9-11 were determined as Z-isomer, while 6 and 8 were defined as E-isomer. A bioassay of the seven derivatives at 10 μM against eight receptor tyrosine kinases (EGFR, HER2, HER4, IGF1R, InsR, VEGFR-2, and PDGFR-α and -β) showed that 8:(Z)-5-(4'-hydroxy-3'methoxybenzylidene)imidazolidine-2,4-dione and 10: (Z)-5-(4'-methoxybenzylidene) imidazolidine-2,4-dione were moderately active against VEGFR-2, with inhibition of 46 and 56%, respectively. In addition, 8 was also active against PDGFR-α and -β, with a 57% inhibition. Further evaluation of 8 and 10 using AutoDock4 showed their binding energy interactions with VEGFR2 (PDB ID: 4AG8) around -6.96 and -7.32 kcal/mol, respectively. Thus, both compounds are potential candidates to be optimized further as inhibitors of angiogenesis blood vessel development. |
| first_indexed | 2025-11-15T01:03:02Z |
| format | Article |
| id | oai:generic.eprints.org:25066 |
| institution | Universiti Kebangasaan Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T01:03:02Z |
| publishDate | 2025 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | oai:generic.eprints.org:250662025-04-14T05:39:41Z http://journalarticle.ukm.my/25066/ Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study Muhammad Naufal, Hidayat, Ika Wiani Hermawati, Elvira Syah, Yana Maolana Al-Anshori, Jamaludin Some hydantoin derivatives have been explored for their potential as anticancer agents by inhibiting receptor tyrosine kinases (RTKs). Benzalhydantoin derivatives were obtained from a two-step reaction: condensation and alkylation reaction. The benzalhydantoin activities were obtained from the enzymatic assay, while the molecular interaction was simulated with molecular docking. Five known compounds (5-9) and two new benzalhydantoin derivatives 10-11 have been synthesized from the appropriate precursors with 4-71% yields. The structures of the compounds were determined mainly by NMR and mass spectral data. From the chemical shift of the H-7’, the configuration of the products 5, 7, 9-11 were determined as Z-isomer, while 6 and 8 were defined as E-isomer. A bioassay of the seven derivatives at 10 μM against eight receptor tyrosine kinases (EGFR, HER2, HER4, IGF1R, InsR, VEGFR-2, and PDGFR-α and -β) showed that 8:(Z)-5-(4'-hydroxy-3'methoxybenzylidene)imidazolidine-2,4-dione and 10: (Z)-5-(4'-methoxybenzylidene) imidazolidine-2,4-dione were moderately active against VEGFR-2, with inhibition of 46 and 56%, respectively. In addition, 8 was also active against PDGFR-α and -β, with a 57% inhibition. Further evaluation of 8 and 10 using AutoDock4 showed their binding energy interactions with VEGFR2 (PDB ID: 4AG8) around -6.96 and -7.32 kcal/mol, respectively. Thus, both compounds are potential candidates to be optimized further as inhibitors of angiogenesis blood vessel development. Penerbit Universiti Kebangsaan Malaysia 2025 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/25066/1/SSB%2016.pdf Muhammad Naufal, and Hidayat, Ika Wiani and Hermawati, Elvira and Syah, Yana Maolana and Al-Anshori, Jamaludin (2025) Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study. Sains Malaysiana, 54 (1). pp. 199-210. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol54num1_2025/contentsVol54num1_2025.html |
| spellingShingle | Muhammad Naufal, Hidayat, Ika Wiani Hermawati, Elvira Syah, Yana Maolana Al-Anshori, Jamaludin Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title | Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title_full | Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title_fullStr | Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title_full_unstemmed | Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title_short | Benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| title_sort | benzalhydantoin derivative-based inhibitors of eight receptor tyrosine kinases: synthesis, in-vitro, and in-silico study |
| url | http://journalarticle.ukm.my/25066/ http://journalarticle.ukm.my/25066/ http://journalarticle.ukm.my/25066/1/SSB%2016.pdf |