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

Autor: Omar A. El-Khouly, Morkos A. Henen, Magda A.-A. El-Sayed, Shahenda M. El-Messery
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-17 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-21277-2
Popis: Abstract Design and synthesis of a new series of benzofuran derivatives has been performed. 1H-NMR, 13C-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 IC50 range of 11–17 µM. Compound 8 inhibited PI3K and VEGFR-2 with IC50 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.
Databáze: Directory of Open Access Journals
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