New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies

Synthesis, antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues

“…The crystal structure of V600E-BRAF kinase in complex with PLX4032 (PDB code: 3OG7) 28,32,33 was obtained from protein data bank (PDB). The binding energies of compound 11 and PLX4032 docked into the active site of V600E-BRAF kinase were À30.65 and À36.11 kcal/mol, respectively ( Figure 5).…”

Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues

“…It was approved by the U.S. Food and Drug Administration (FDA) for treatment of late-stage melanoma, so inhibition of B-RAFV600E kinase is a very potential avenue for the treatment of melanoma [14][15][16][17][18] . On the other hand, several heterocyclic compounds are intensively studied to enhance the range of anticancer agents [17][18][19][20][21][22][23][24] . During the last decade, lots of pyrazole anticancer agents were discovered, and such pyrazole core has increasingly attracted the attention of synthetic medicinal chemists 17,18,[20][21][22][23][24] .…”

“…Moreover, B-RAF mutations are found in all melanoma subtypes but are most common in melanomas derived from skin without chronic sun-induced damage. Melanoma is the most aggressive type of skin cancer in which B-RAFV600E kinase is over-expressed in 63% of all malignant melanomas [14][15][16][17][18] . Vemurafenib (PLX4032) is a drug which targets inhibition of B-RAFV600E kinase [14][15][16][17][18] .…”

“…Melanoma is the most aggressive type of skin cancer in which B-RAFV600E kinase is over-expressed in 63% of all malignant melanomas [14][15][16][17][18] . Vemurafenib (PLX4032) is a drug which targets inhibition of B-RAFV600E kinase [14][15][16][17][18] . It was approved by the U.S. Food and Drug Administration (FDA) for treatment of late-stage melanoma, so inhibition of B-RAFV600E kinase is a very potential avenue for the treatment of melanoma [14][15][16][17][18] .…”

“…Vemurafenib (PLX4032) is a drug which targets inhibition of B-RAFV600E kinase [14][15][16][17][18] . It was approved by the U.S. Food and Drug Administration (FDA) for treatment of late-stage melanoma, so inhibition of B-RAFV600E kinase is a very potential avenue for the treatment of melanoma [14][15][16][17][18] . On the other hand, several heterocyclic compounds are intensively studied to enhance the range of anticancer agents [17][18][19][20][21][22][23][24] .…”