Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer

Design and synthesis of a new series of benzofuran derivatives has been performed. 1 H-NMR, 13 C-NMR, elemental analysis, and IR were used to confirm the structures of the produced compounds. Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), epithelioid carcinoma cervical cancer...

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Vydáno v:Scientific reports Ročník 12; číslo 1; s. 17104 - 17
Hlavní autoři: El-Khouly, Omar A., Henen, Morkos A., El-Sayed, Magda A.-A., El-Messery, Shahenda M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 12.10.2022
Nature Publishing Group
Nature Portfolio
Témata:
1-Phosphatidylinositol 3-kinase
631/114
631/154
631/1647
631/535
631/67
639/638
692/4028
692/699
Antineoplastic Agents - chemistry
Antitumor activity
Benzofuran
Benzofurans - pharmacology
Benzofurans - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Cell Proliferation
Cervical cancer
Cervix
Computer applications
Drug Design
Drug Screening Assays, Antitumor
Female
Hepatocellular carcinoma
Humanities and Social Sciences
Humans
Hybrids
Inhibitor drugs
Liver cancer
Mammary gland
MCF-7 Cells
Molecular Docking Simulation
Molecular Structure
multidisciplinary
NMR
Nuclear magnetic resonance
Phosphatidylinositol 3-Kinases - metabolism
Prostate cancer
Protein Kinase Inhibitors - chemistry
Science
Science (multidisciplinary)
Sorafenib - pharmacology
Structure-Activity Relationship
Tumor cell lines
Uterine Cervical Neoplasms
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Vascular endothelial growth factor receptors
ISSN:2045-2322, 2045-2322
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Shrnutí:Design and synthesis of a new series of benzofuran derivatives has been performed. 1 H-NMR, 13 C-NMR, elemental analysis, and IR were used to confirm the structures of the produced compounds. Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), epithelioid carcinoma cervical cancer (Hela), and human prostate cancer are used to test anticancer activity (PC3). In compared to DOX (4.17–8.87 µM), Compound 8 demonstrated the highest activity against HePG and PC3 cell lines, with an IC 50 range of 11–17 µM. Compound 8 inhibited PI3K and VEGFR-2 with IC 50 values of 2.21 and 68 nM, respectively, compared to 6.18 nM for compound LY294002 and 31.2 nM for compound sorafenib as PI3K and VEGFR-2 reference inhibitors, selectively. The molecular docking and binding affinity of the generated compounds were estimated and studied computationally utilizing molecular operating environment software as a PI3K and VEGFR-2 inhibitor (MOE). In conclusion, compound 8 exhibited significant action against hepatocellular and cervical cancer cell lines. Mechanistic study showed that it had a dual inhibitory effect against PI3K and VEGFR-2.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-21277-2