Azizah M Malebari1, Rakia Abd Alhameed2, Zainab Almarhoon2, Muhammad Farooq3, Mohammad A M Wadaan3,4, Anamika Sharma5,6, Beatriz G de la Torre5,6, Fernando Albericio2,6,7,8, Ayman El-Faham2,9. 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. 2. Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. 3. Bio-Products Research Chair, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. 4. Deanship of Postgraduate Studies and Scientific Research, Almaarefa University, Riyadh 11597, Saudi Arabia. 5. KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa. 6. Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa. 7. CIBER-BBN (Networking Centre on Bioengineering, Biomaterials and Nanomedicine) and Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain. 8. Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain. 9. Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 12321, Egypt.
Abstract
Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a-which contains morpholine, aniline, and glycylglycinate methyl ester-showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.
Several derivatives containing class="Chemical">morpholine/n class="Chemical">piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two humanbreast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a-which contains morpholine, aniline, and glycylglycinate methyl ester-showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.
Authors: John A Katzenellenbogen; Christopher G Mayne; Benita S Katzenellenbogen; Geoffrey L Greene; Sarat Chandarlapaty Journal: Nat Rev Cancer Date: 2018-06 Impact factor: 60.716
Authors: Ihab Shawish; Assem Barakat; Ali Aldalbahi; Azizah M Malebari; Mohamed S Nafie; Adnan A Bekhit; Amgad Albohy; Alamgir Khan; Zaheer Ul-Haq; Matti Haukka; Beatriz G de la Torre; Fernando Albericio; Ayman El-Faham Journal: ACS Omega Date: 2022-07-07