Zhonghai Tang1,2, Ulyana Muñoz Acuña1,3, Nelson Freitas Fernandes1,3, Somsundaram Chettiar3, Pui-Kai Li3, Esperanza Carcache DE Blanco3,4. 1. Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A. 2. Department of Food Quality and Safety, College of Food Science and Technology,zzm321990Hunan Agricultural University, Changsha, P.R. China 3. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A. 4. Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A. carcache-de-blan.1@osu.edu.
Abstract
BACKGROUND/AIM: Cancer is a leading cause of death. Hence, this study aimed at the optimization of niclosamide derivatives for the development of new potential anticancer agents. MATERIALS AND METHODS: Niclosamide derivatives were synthesized and tested against a panel of human cancer cells: MDA and MCF7 breast cancer cells, PC3 and DU-145 prostate cancer cells, Hela cervical cancer cells, and HL-60 acute promyelocytic leukemia cells. They were also tested in nuclear factor-ĸappa B (NFĸB), V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and mitochondria transmembrane potential (MTP) assays. RESULTS: N-(3,5-Bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide exhibited the most significant cytotoxicity against HL-60 cells, while 5-chloro-N-(2-chlorophenyl)-2-hydroxybenzamide was the most active in the NFĸB assay and 5-chloro-N-(3,5-difluorophenyl)-2-hydroxybenzamide in the MTP assay. 5-chloro-N-(2-chloro-4-(trifluoromethyl) phenyl)-2-hydroxybenzamide and 5-chloro-2-hydroxy-N-(4-hydroxyphenyl)benzamide inhibited both HL-60 cell proliferation and NFĸB. CONCLUSION: In-depth study of the most promising compounds is highly encouraged to further develop into potential anticancer agents those derivatives found to be significantly active. Copyright
BACKGROUND/AIM: Cancer is a leading cause of death. Hence, this study aimed at the optimization of niclosamide derivatives for the development of new potential anticancer agents. MATERIALS AND METHODS:Niclosamide derivatives were synthesized and tested against a panel of humancancer cells: MDA and MCF7 breast cancer cells, PC3 and DU-145 prostate cancer cells, Hela cervical cancer cells, and HL-60 acute promyelocytic leukemia cells. They were also tested in nuclear factor-ĸappa B (NFĸB), V-Ki-ras2 Kirsten ratsarcoma viral oncogene (KRAS), and mitochondria transmembrane potential (MTP) assays. RESULTS:N-(3,5-Bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide exhibited the most significant cytotoxicity against HL-60 cells, while 5-chloro-N-(2-chlorophenyl)-2-hydroxybenzamide was the most active in the NFĸB assay and 5-chloro-N-(3,5-difluorophenyl)-2-hydroxybenzamide in the MTP assay. 5-chloro-N-(2-chloro-4-(trifluoromethyl) phenyl)-2-hydroxybenzamide and 5-chloro-2-hydroxy-N-(4-hydroxyphenyl)benzamide inhibited both HL-60 cell proliferation and NFĸB. CONCLUSION: In-depth study of the most promising compounds is highly encouraged to further develop into potential anticancer agents those derivatives found to be significantly active. Copyright
Authors: Hee-Don Chae; Nick Cox; Gary V Dahl; Norman J Lacayo; Kara L Davis; Samanta Capolicchio; Mark Smith; Kathleen M Sakamoto Journal: Oncotarget Date: 2017-12-31