Synthesis, and potent dual bioactivity of quinazoline–1,2,4-triazole hybrids: Novel anticancer and antimicrobial agents

Abdel-Rahman, Adel A.-H.; Nagy, Ibrahim M.; Shallan, Yasmeen A.; Swelam, Samira; Soliman, Abdelmohsen; Wahba, Nancy E.; Hawata, Mohamed Abdallah

doi:10.21608/ejchem.2025.413524.12180

Synthesis, and potent dual bioactivity of quinazoline–1,2,4-triazole hybrids: Novel anticancer and antimicrobial agents

Articles in Press

Document Type : Original Article

Authors

¹ Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, EGYPT.

² Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, 32511 Egypt

³ Photochemistry Department, National Research Centre, 33 El-Bohouth St., Dokki - 12622, Giza, Egypt

⁴ Therapeutic Chemistry dept. National Research Centre, Dokki, Giza, Egypt

⁵ Faculty of science menoufia university shebien ElKoom Egypt

10.21608/ejchem.2025.413524.12180

Abstract

A novel series of quinazoline–1,2,4-triazole hybrids was synthesized via modified synthetic methodologies, incorporating structural motifs such as triazolothiadiazole, glycosyl, Schiff base, and Mannich derivatives. These compounds were evaluated for dual anticancer and antimicrobial activities. The anticancer potential of the synthesized hybrids was evaluated against MCF7, HCT116, and DU145 human cancer cell lines. Among the tested compounds, 14 and 11a exhibited the most pronounced cytotoxicity, comparable to doxorubicin, through the induction of apoptosis confirmed by Annexin V/PI flow cytometry and a significant rise in caspase-3 activity (2.9- and 2.5-fold, respectively). Cellular target engagement assays demonstrated that compound 14 enhanced Myc protein thermal stability (+3.5 °C) and reduced Myc-dependent luciferase activity by 65 ± 8%, indicating inhibition of Myc-driven transcriptional activity. In antimicrobial assays, both 14 and 11a displayed broad-spectrum efficacy against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus, with inhibition zones of 27–29 mm and MIC values of 4–6 µg/mL. Furthermore, they strongly inhibited Dihydrofolate Reductase (DHFR) from bacterial and fungal sources (up to 68.4 ± 2.3%), consistent with molecular docking findings (ΔG = −9.5 to −11.0 kcal/mol) showing key hydrogen bonding and π–π interactions within the DHFR active site. Overall, compounds 14 and 11a demonstrated excellent multitarget activity by simultaneously modulating Myc oncogenic signaling and DHFR-mediated microbial metabolism, representing promising scaffolds for further drug development.

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