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

Autor: El-Khouly OA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.; Faculty of Pharmacy, New Mansoura University, P.O. Box 35712, New Mansoura, Egypt., Henen MA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.; Department of Biochemistry and Molecular Genetics, University of Colorado, Denver, USA., El-Sayed MA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, P.O. Box 34518, New Damietta, Egypt., El-Messery SM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt. habib2001@mans.edu.eg.; Faculty of Pharmacy, New Mansoura University, P.O. Box 35712, New Mansoura, Egypt. habib2001@mans.edu.eg.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Oct 12; Vol. 12 (1), pp. 17104. Date of Electronic Publication: 2022 Oct 12.
DOI: 10.1038/s41598-022-21277-2
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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