New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors
Abstract A new series of glycosyl heterocyclic scaffolds, 5a-10b with N-glycosidic linkage, were synthesized, starting with 2-acetyl-1H-benzimidazole as a precursor of the propargyl-derived substrates (2) and (3), which were then converted to the target 1,2,3-triazole glycosides (8a-10b) bearing unp...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-96675-3 |
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| author | Aladdin M. Srour Mohamed N. El-Bayaa Ahmed Temirak Asmaa L. Alanzy Hanem M. Awad Asmaa Saleh Mahmoud G. Saleh Wael A. El-Sayed |
| author_facet | Aladdin M. Srour Mohamed N. El-Bayaa Ahmed Temirak Asmaa L. Alanzy Hanem M. Awad Asmaa Saleh Mahmoud G. Saleh Wael A. El-Sayed |
| author_sort | Aladdin M. Srour |
| collection | DOAJ |
| description | Abstract A new series of glycosyl heterocyclic scaffolds, 5a-10b with N-glycosidic linkage, were synthesized, starting with 2-acetyl-1H-benzimidazole as a precursor of the propargyl-derived substrates (2) and (3), which were then converted to the target 1,2,3-triazole glycosides (8a-10b) bearing unprotected hydroxyl groups. The new chemical entities have been assessed for their cytotoxic properties on diverse human cancer cell lines, namely HepG-2 (human liver cancer), HCT-116 (human colorectal), and MCF-7 (human breast cancer), in addition to a human normal cell line (BJ-1), following the LDH assay and with erlotinib and doxorubicin as the standard references. Most of the tested compounds demonstrated potent activity, particularly the triazole glycosides 6b, 7b, 8b, 9a, 9b, 10a, and 10b. Compound 9a was the best against all targeted cell lines, particularly HepG-2 and HCT-116, by IC50 values of 1.64 ± 0.11 and 5.00 ± 0.51 µM, superior to that of erlotinib, IC50 = 2.07 ± 0.07 and 5.14 ± 0.33 µM, respectively. Furthermore, it showed a safe profile against the tested normal cell line BJ-1. The triazole glycosides 8a-10b were investigated to assess their capability to inhibit EGFR. Remarkably, 9a and 9b exhibited noteworthy inhibitory activity against EGFR (IC50 = 0.069 ± 0.003 and 0.075 ± 0.003 µM, respectively) in comparison with erlotinib, the reference drug (0.048 ± 0.002 µM). Molecular docking confirmed these findings, suggesting that the incorporation of the α,β-unsaturated ketone function enhances compounds’ stability within the EGFR active site. Thus, these results indicate that compounds 9a and 9b disclosed potential anti-cancer agents targeting EGFR kinase. |
| format | Article |
| id | doaj-art-dbc3efcbeeaf4adfbef53e403d68b29b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dbc3efcbeeaf4adfbef53e403d68b29b2025-08-20T03:42:29ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-96675-3New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitorsAladdin M. Srour0Mohamed N. El-Bayaa1Ahmed Temirak2Asmaa L. Alanzy3Hanem M. Awad4Asmaa Saleh5Mahmoud G. Saleh6Wael A. El-Sayed7Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research CentreDepartment of Chemistry, College of Science, Qassim UniversityChemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research CentreDepartment of Chemistry, College of Science, Qassim UniversityTanning Materials and Leather Technology Department, National Research CentreDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman UniversityDepartment of Chemistry, College of Science, Northern Border UniversityPhotochemistry Department, National Research CentreAbstract A new series of glycosyl heterocyclic scaffolds, 5a-10b with N-glycosidic linkage, were synthesized, starting with 2-acetyl-1H-benzimidazole as a precursor of the propargyl-derived substrates (2) and (3), which were then converted to the target 1,2,3-triazole glycosides (8a-10b) bearing unprotected hydroxyl groups. The new chemical entities have been assessed for their cytotoxic properties on diverse human cancer cell lines, namely HepG-2 (human liver cancer), HCT-116 (human colorectal), and MCF-7 (human breast cancer), in addition to a human normal cell line (BJ-1), following the LDH assay and with erlotinib and doxorubicin as the standard references. Most of the tested compounds demonstrated potent activity, particularly the triazole glycosides 6b, 7b, 8b, 9a, 9b, 10a, and 10b. Compound 9a was the best against all targeted cell lines, particularly HepG-2 and HCT-116, by IC50 values of 1.64 ± 0.11 and 5.00 ± 0.51 µM, superior to that of erlotinib, IC50 = 2.07 ± 0.07 and 5.14 ± 0.33 µM, respectively. Furthermore, it showed a safe profile against the tested normal cell line BJ-1. The triazole glycosides 8a-10b were investigated to assess their capability to inhibit EGFR. Remarkably, 9a and 9b exhibited noteworthy inhibitory activity against EGFR (IC50 = 0.069 ± 0.003 and 0.075 ± 0.003 µM, respectively) in comparison with erlotinib, the reference drug (0.048 ± 0.002 µM). Molecular docking confirmed these findings, suggesting that the incorporation of the α,β-unsaturated ketone function enhances compounds’ stability within the EGFR active site. Thus, these results indicate that compounds 9a and 9b disclosed potential anti-cancer agents targeting EGFR kinase.https://doi.org/10.1038/s41598-025-96675-3Benzimidazole1,2,3-TriazoleAnti-cancerLDF assayEGFRCytotoxicity |
| spellingShingle | Aladdin M. Srour Mohamed N. El-Bayaa Ahmed Temirak Asmaa L. Alanzy Hanem M. Awad Asmaa Saleh Mahmoud G. Saleh Wael A. El-Sayed New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors Scientific Reports Benzimidazole 1,2,3-Triazole Anti-cancer LDF assay EGFR Cytotoxicity |
| title | New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors |
| title_full | New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors |
| title_fullStr | New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors |
| title_full_unstemmed | New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors |
| title_short | New benzimidazole-triazole glycoconjugates as anti-cancer agents and EGFR inhibitors |
| title_sort | new benzimidazole triazole glycoconjugates as anti cancer agents and egfr inhibitors |
| topic | Benzimidazole 1,2,3-Triazole Anti-cancer LDF assay EGFR Cytotoxicity |
| url | https://doi.org/10.1038/s41598-025-96675-3 |
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