Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer
- Sci Rep. 2022 Oct 12;12(1):17104. doi: 10.1038/s41598-022-21277-2.
- 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.
- 2. Faculty of Pharmacy, New Mansoura University, P.O. Box 35712, New Mansoura, Egypt.
- 3. Department of Biochemistry and Molecular Genetics, University of Colorado, Denver, USA.
- 4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, P.O. Box 34518, New Damietta, Egypt.
- 5. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt. [email protected].
- 6. Faculty of Pharmacy, New Mansoura University, P.O. Box 35712, New Mansoura, Egypt. [email protected].
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.