2. Academic Validation
  3. Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and In Vitro Cytotoxicity

Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and In Vitro Cytotoxicity

  • ACS Med Chem Lett. 2024 Nov 25;15(12):2150-2157. doi: 10.1021/acsmedchemlett.4c00438.
Akram H Abd El-Haleem 1,  Manar Abd El-Karim Kassem 1,  Mohamed R Elnagar 2 3,  Safinaz E-S Abbas 4,  Ahmed M El Kerdawy 4 5,  Ahmed K B A W Farouk 4
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Sixth of October City, Giza 77, Egypt.
  • 2 Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11823, Egypt.
  • 3 Department of Pharmacology, College of Pharmacy, The Islamic University, Najaf 54001, Iraq.
  • 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
  • 5 School of Health and Care Sciences, College of Health and Science, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln, Lincolnshire LN6 7DL, United Kingdom.
PMID: 39691520 DOI: 10.1021/acsmedchemlett.4c00438
Abstract

New derivatives 4a-d, 6, 7a-d, 8a-c, 9, 11a, 11b, 12a-f, 13a-c, and 14 were synthesized and evaluated for their VEGFR-2 inhibition. Compounds 4c, 7b, and 7c showed remarkable Enzyme inhibition (IC50 = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC50 = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 Cancer cell lines in addition to WI-38. Compound 7b displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC50 = 6.66 and 8.51 μM) compared to sorafenib (IC50 = 6.60 and 8.78 μM). Cell cycle analysis and apoptotic assay of 7b in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of Apoptosis. Western blot analysis of compound 7b revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of 7b showed inhibition of wound closure. Additionally, molecular modeling studies of compounds 4c, 7b, and 7c were carried out.

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