| Autor: |
Mohamed AH; Chemistry Department, Faculty of Science, Minia University, El-Minia, Egypt., Alshammari MB; Chemistry Department, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, Al-Kharij, Saudi Arabia., Aly AA; Chemistry Department, Faculty of Science, Minia University, El-Minia, Egypt., Sadek KU; Chemistry Department, Faculty of Science, Minia University, El-Minia, Egypt., Ahmad A; Chemistry Department, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, Al-Kharij, Saudi Arabia., Aziz EA; Chemistry Department, Faculty of Science, Minia University, El-Minia, Egypt., El-Yazbi AF; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., El-Agroudy EJ; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Abdelaziz ME; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. |
| Abstrakt: |
In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2 H )-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin , respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors. |
