Scaffold hopping and redesign approaches for quinazoline based urea derivatives as potent VEGFR-2 inhibitors

Hadi, Soha R. Abd El; Lasheen, Deena S.; Soliman, Dalia H.; Elrazaz, Eman Z.; Abouzid, Khaled A. M.

doi:10.1016/j.bioorg.2020.103961

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…Abd El Hadi et al (2020) lately generated an extreme of quinazoline compounds containing urea that operate as effective VEGFR-2 inhibitors. The amide derivative 9 (Z = H, X = NH, R = Me, R 1 = 3-Me) demonstrated significant nanomolar VEGFR-2 suppression with an IC 50 value of 12.1 nm, which was more potent than the reference sorafenib (IC 50 = 78.9 nm).…”

Section: Anticancer Quinazolinesmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of quinazolines

Gomaa

2022

Chem Biol Drug Des

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Quinazoline heterocycles are critical in the development of medications.Quinazoline derivatives have been intensively researched, providing a wide range of compounds with diverse biological roles. The quinazoline nucleus has garnered a lot of attention in medical chemistry in recent years. It was assumed to be a pharmacophore component in the development of physiologically interesting drugs. This review is an attempt to increase the potential of quinazoline by highlighting a wide range of advancements demonstrated by numerous derivatives of the quinazoline moiety, as well as focusing on diverse pharmacological actions of the quinazoline moiety. This review compiles recent studies on the quinazoline moiety described in the literature by researchers.

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Section: Anticancer Quinazolinesmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of quinazolines

Gomaa

2022

Chem Biol Drug Des

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“…[14,32,33] Furthermore, several studies reported the use of diaryl urea moiety-based frameworks for targeting VEGFR-2 kinase and subsequently reducing angiogenesis. [23,[34][35][36] Patterson et al, [37] reported the diaryl urea pyrimidine derivative (VIII) which demonstrated VEGFR-2 and p38α inhibitory activities with IC 50 of 0.40 and 0.80 µM, respectively. The diaryl urea ethylpiperazine derivative (IX) was reported as a VEGFR-2 inhibitor showing an IC 50 of 0.25 µM.…”

Section: Introductionmentioning

confidence: 99%

“…The diaryl urea quinazoline derivatives (XIII and XIV) were reported as VEGFR-2 inhibitors with IC 50 of 0.12 and 0.15 µM, respectively. [36] Azimian et al, [42] synthesized the diaryl urea derivative (XV) that inhibited both the VEGFR-2 phosphorylation and RAF/MEK/ERK pathway at 10 µM (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Novel 2‐oxo‐2‐phenylethoxy and benzyloxy diaryl urea hybrids as VEGFR‐2 inhibitors: Design, synthesis, and anticancer evaluation

Ghannam

Kerdawy

Mounier

et al. 2022

Archiv der Pharmazie

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Two series of diaryl urea derivatives, 6a-k and 7a-n, were synthesized. All the newly synthesized compounds were tested against the NCI (US) cancer cell lines via SRB assay. The p-chloro-m-trifluoromethyl phenyl derivatives 6e-g and 7e-g showed the most potent cytotoxic activity with a GI 50 value range of 1.2-15.9 µM. Furthermore, the p-fluorobenzyloxy diaryl urea derivative 7g revealed the most potent cytotoxicity against eight cancer cell lines in the MTT assay with IC 50 values below 5 µM. Compounds 6a-k and 7a-n were tested for their vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitory activities. The p-chloro-mtrifluoromethyl diaryl urea benzyloxy derivatives 7e-i and the p-methoxydiaryl urea benzyloxy derivatives 7k, 7l, and 7n were found to be the most active compounds as VEGFR-2 inhibitors in the benzyloxy series 7, with an IC 50 range of 0.09-4.15 µM. In the 2-oxo-2-phenylethoxy series 6, compounds 6e-g and 6i were reported with IC 50 values of 0.94, 0.54, 2.71, and 4.81 µM, respectively. Moreover, compounds 7e and 7g induced apoptosis, causing cell cycle arrest in the G2/M phase. In addition, 7gshowed an antimigratory effect in A-375 cells and inhibited the VEGFR-2 expression in an immunohistofluorescence study. Molecular docking simulations on VEGFR-2 as well as ADME properties prediction were also performed.

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“…Vascular endothelial growth factor (VEGFR) has been defined as a member of tyrosine kinases and is considered a suitable tool for cancer treatment because of its predominant function in tumor angiogenesis. [6,7] Angiogenesis is a physiological formation of new blood vessels from already existing ones involving (i) endothelial cell proliferation, (ii) migration, (iii) basement membrane degeneration, and (iv) new tube formation. [8] Due to the role of angiogenesis in physiological processes including embryogenesis, inflammation, and wound healing, angiogenesis inhibitors have been clinically used for the treatment of several diseases such as cancer, autoimmune disorders, retinopathy, obesity, and macular degeneration.…”

Section: Introductionmentioning

confidence: 99%

Thienopyrimidine‐based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity

Mohammadian

Bakhshaiesh

Jouyban

et al. 2022

Archiv der Pharmazie

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An important role has been considered for the vascular endothelial growth factor receptor 2 (VEGFR‐2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5–15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR‐2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h.

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Scaffold hopping and redesign approaches for quinazoline based urea derivatives as potent VEGFR-2 inhibitors

Cited by 17 publications

References 30 publications

A comprehensive review of recent advances in the biological activities of quinazolines

A comprehensive review of recent advances in the biological activities of quinazolines

Novel 2‐oxo‐2‐phenylethoxy and benzyloxy diaryl urea hybrids as VEGFR‐2 inhibitors: Design, synthesis, and anticancer evaluation

Thienopyrimidine‐based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity

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