| Autor: |
Eldehna WM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt., Salem R; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt., Elsayed ZM; Scientific Research and Innovation Support Unit, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt., Al-Warhi T; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Knany HR; Department of Pharmacognosy, College of Pharmacy, Mansoura University, Mansoura, Egypt., Ayyad RR; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt., Traiki TB; Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh, Saudi Arabia., Abdulla MH; Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh, Saudi Arabia., Ahmad R; Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh, Saudi Arabia., Abdel-Aziz HA; Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, Egypt., El-Haggar R; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt. |
| Abstrakt: |
In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates ( 5a-e and 7a-i ) was designed and synthesised. The anticancer activity for compounds ( 5b-d , 7a, 7b, 7d and 7g ) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates ( 5a-e and 7a-i ) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC 50 = 8.7 and 9.4 µM ( 5a ), and 6.5 and 9.8 µM for ( 5d ), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis. |
