2. Academic Validation
  3. Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies

Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies

  • Future Med Chem. 2025 Mar;17(5):529-541. doi: 10.1080/17568919.2025.2468146.
Reda R Mabrouk 1 2,  Hazem A Mahdy 1,  Abdallah E Abdallah 1,  Ismail Celik 3,  Abdelsalam Mohamed Abdelsalam Ouf 4,  Mariam K Alamoudi 5,  Aisha Alnami 6 7,  Maged Mohammed Saleh Al Ward 1 8,  Ahmed B M Mehany 9,  Mohamed Ayman El-Zahabi 1
Affiliations

Affiliations

  • 1 Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
  • 2 Directorate of Health Affairs in Buhaira-Clinical Research Department, Ministry of Health and Population, Damanhour, Egypt.
  • 3 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
  • 4 Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Assiut, Egypt.
  • 5 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 7 Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 8 Medicinal Chemistry Department, Faculty of Pharmacy, Al Razi University, Sana'a, Yemen.
  • 9 Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt.
PMID: 39995350 DOI: 10.1080/17568919.2025.2468146
Abstract

Background: New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various Cancer cell lines, prompted by the need for effective Anticancer agents.

Research design and methods: All synthesized compounds were confirmed by spectroscopic methods and tested in vitro for their inhibitory activities against hepatocellular carcinoma (HepG-2), breast Cancer (MCF-7), and prostate Cancer (PC3) cell lines. Ten compounds were tested in vitro to explore their inhibitory activity against the VEGFR-2. Additionally, various studies were investigated for the most active compound 6, including cell cycle analysis, apoptotic activity assessment, effect on gene expression, safety profiling, molecular docking, MD simulation, and ADMET analysis.

Results: Compounds 3a, 3c, and 6 exhibited higher cytotoxic activity against MCF-7 than doxorubicin. Compound 6 was most potent, arresting the cell cycle at G1 phase and showing proapoptotic action. It significantly inhibited VEGFR-2 and altered gene expression, promoting Bax, P21, and P53 while downregulating Bcl-2. Docking and MD simulations indicated stable interaction with VEGFR-2, safety, and ADMET profiles suggested favorable drug-likeness and safety.

Conclusions: Compound 6 has shown promising Anticancer potential, particularly against breast Cancer, but further research is needed to confirm these findings and address long-term safety.

Keywords

ADMET; MCF7; Piperazine; Triazoloquinazoline; VEGFR2; angiogenesis; breast cancer.

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