Design and synthesis of new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as VEGFR2 inhibitors affecting the Bax/Bcl-2 in the HepG2 cancer cells.
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| Title: | Design and synthesis of new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as VEGFR2 inhibitors affecting the Bax/Bcl-2 in the HepG2 cancer cells. |
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| Authors: | Youssef, Mohamed F.1 (AUTHOR) mohamed_gomma@science.suez.edu.eg, Eltamany, Elsayed H.1 (AUTHOR), Boraei, Ahmed T.A.1 (AUTHOR), Attia, Ahmed E.1 (AUTHOR), Nafie, Mohamed S.1,2 (AUTHOR) mohamed_nafie@science.suez.edu.eg |
| Source: | Journal of Molecular Structure. Mar2026, Vol. 1355, pN.PAG-N.PAG. 1p. |
| Subjects: | Vascular endothelial growth factor antagonists, Apoptosis, Antineoplastic agents, Hepatocellular carcinoma, Organonitrogen compounds, Cytotoxins, Chemical synthesis, Bcl-2 proteins |
| Abstract: | • Novel substituted Thieno[2,3-d]Pyrimidine derivatives were synthesized and fully characterized. • Interestingly, compound 7 exhibited the most potent cytotoxicity against MCF-7 and HepG-2 cells, with IC 50 values of 0.09 µM. • Compound 7 exhibited promising VEGFR2 inhibition, with an IC 50 value of 0.098 µM. • Compound 7 induced apoptosis in the HepG2 cancer cells by 30.74-fold, arresting the cell cycle at the G1-phase. • Compound 7 treatment affected the Bax/Bcl-2 in gene expression analysis. There is a need to synthesize new bioactive compounds to fight cancer. As a result, ethyl 2-amino-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate 1 used for the synthesis of 2-thioxo-thieno[2,3-d]pyrimidin-4-one 2 which benzylated to afford 2-(benzylthio)-thieno[2,3-d]pyrimidin-4-one 3. Chlorination of 3 yielded 2-(benzylthio)-4‑chloro-thieno[2,3- d ]pyrimidine 4 which thionated to furnish 2-(benzylthio)-thieno[2,3-d]pyrimidin-4-thione 5. Alkylation of 5 yielded the S-alkylated product 6 which on hydrazinolysis afforded 4-hydrazino-thienopyrimidine 7. Amination of 4‑chloro-thieno[2,3- d ]pyrimidine 4 yielded the 4-aminated products 8a-b. Reaction of 4-hydrazino-thienopyrimidine scaffold 7 with CS 2 , phthalic anhydride, succinic anhydride, acetyl acetone, chloroacetyl chloride, and benzoyl chloride, yielding products 10 – 17, respectively. The cytotoxicity of the synthesized compounds was assessed against MCF-7 and HepG2 cancer cell lines using the MTT assay. Approximately sixteen compounds showed promising antiproliferative potential with IC 50 in a range from 0.09 µM to 1.96 µM. Interestingly, compound 7 exhibited the most potent cytotoxicity against MCF-7 and HepG2 cells, with IC 50 values of 0.09 µM. Notably, compound 7 exhibited promising VEGFR2 inhibition, with an IC 50 value of 0.098 µM and an inhibition percentage of 86.8 %. Compound 7 treatment altered Bax/Bcl-2 gene expression in HepG2 cancer cells, inducing apoptosis by 30.74-fold and halting the cell cycle at the G1-phase. Accordingly, compound 7 can be further validated as a potent anticancer agent in an in vivo animal model. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Molecular Structure is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 190931817 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Design and synthesis of new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as VEGFR2 inhibitors affecting the Bax/Bcl-2 in the HepG2 cancer cells. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Youssef%2C+Mohamed+F%2E%22">Youssef, Mohamed F.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> mohamed_gomma@science.suez.edu.eg</i><br /><searchLink fieldCode="AR" term="%22Eltamany%2C+Elsayed+H%2E%22">Eltamany, Elsayed H.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Boraei%2C+Ahmed+T%2EA%2E%22">Boraei, Ahmed T.A.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Attia%2C+Ahmed+E%2E%22">Attia, Ahmed E.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nafie%2C+Mohamed+S%2E%22">Nafie, Mohamed S.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> mohamed_nafie@science.suez.edu.eg</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Molecular+Structure%22">Journal of Molecular Structure</searchLink>. Mar2026, Vol. 1355, pN.PAG-N.PAG. 1p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Vascular+endothelial+growth+factor+antagonists%22">Vascular endothelial growth factor antagonists</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink><br /><searchLink fieldCode="DE" term="%22Antineoplastic+agents%22">Antineoplastic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Hepatocellular+carcinoma%22">Hepatocellular carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Organonitrogen+compounds%22">Organonitrogen compounds</searchLink><br /><searchLink fieldCode="DE" term="%22Cytotoxins%22">Cytotoxins</searchLink><br /><searchLink fieldCode="DE" term="%22Chemical+synthesis%22">Chemical synthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Bcl-2+proteins%22">Bcl-2 proteins</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: • Novel substituted Thieno[2,3-d]Pyrimidine derivatives were synthesized and fully characterized. • Interestingly, compound 7 exhibited the most potent cytotoxicity against MCF-7 and HepG-2 cells, with IC 50 values of 0.09 µM. • Compound 7 exhibited promising VEGFR2 inhibition, with an IC 50 value of 0.098 µM. • Compound 7 induced apoptosis in the HepG2 cancer cells by 30.74-fold, arresting the cell cycle at the G1-phase. • Compound 7 treatment affected the Bax/Bcl-2 in gene expression analysis. There is a need to synthesize new bioactive compounds to fight cancer. As a result, ethyl 2-amino-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate 1 used for the synthesis of 2-thioxo-thieno[2,3-d]pyrimidin-4-one 2 which benzylated to afford 2-(benzylthio)-thieno[2,3-d]pyrimidin-4-one 3. Chlorination of 3 yielded 2-(benzylthio)-4‑chloro-thieno[2,3- d ]pyrimidine 4 which thionated to furnish 2-(benzylthio)-thieno[2,3-d]pyrimidin-4-thione 5. Alkylation of 5 yielded the S-alkylated product 6 which on hydrazinolysis afforded 4-hydrazino-thienopyrimidine 7. Amination of 4‑chloro-thieno[2,3- d ]pyrimidine 4 yielded the 4-aminated products 8a-b. Reaction of 4-hydrazino-thienopyrimidine scaffold 7 with CS 2 , phthalic anhydride, succinic anhydride, acetyl acetone, chloroacetyl chloride, and benzoyl chloride, yielding products 10 – 17, respectively. The cytotoxicity of the synthesized compounds was assessed against MCF-7 and HepG2 cancer cell lines using the MTT assay. Approximately sixteen compounds showed promising antiproliferative potential with IC 50 in a range from 0.09 µM to 1.96 µM. Interestingly, compound 7 exhibited the most potent cytotoxicity against MCF-7 and HepG2 cells, with IC 50 values of 0.09 µM. Notably, compound 7 exhibited promising VEGFR2 inhibition, with an IC 50 value of 0.098 µM and an inhibition percentage of 86.8 %. Compound 7 treatment altered Bax/Bcl-2 gene expression in HepG2 cancer cells, inducing apoptosis by 30.74-fold and halting the cell cycle at the G1-phase. Accordingly, compound 7 can be further validated as a potent anticancer agent in an in vivo animal model. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Molecular Structure is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.molstruc.2025.144780 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 1 StartPage: N.PAG Subjects: – SubjectFull: Vascular endothelial growth factor antagonists Type: general – SubjectFull: Apoptosis Type: general – SubjectFull: Antineoplastic agents Type: general – SubjectFull: Hepatocellular carcinoma Type: general – SubjectFull: Organonitrogen compounds Type: general – SubjectFull: Cytotoxins Type: general – SubjectFull: Chemical synthesis Type: general – SubjectFull: Bcl-2 proteins Type: general Titles: – TitleFull: Design and synthesis of new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as VEGFR2 inhibitors affecting the Bax/Bcl-2 in the HepG2 cancer cells. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Youssef, Mohamed F. – PersonEntity: Name: NameFull: Eltamany, Elsayed H. – PersonEntity: Name: NameFull: Boraei, Ahmed T.A. – PersonEntity: Name: NameFull: Attia, Ahmed E. – PersonEntity: Name: NameFull: Nafie, Mohamed S. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 03 Text: Mar2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 00222860 Numbering: – Type: volume Value: 1355 Titles: – TitleFull: Journal of Molecular Structure Type: main |
| ResultId | 1 |
