TY - JOUR T1 - Structure–Activity Relationship of Niclosamide Derivatives JF - Anticancer Research JO - Anticancer Res SP - 2839 LP - 2843 VL - 37 IS - 6 AU - ZHONGHAI TANG AU - ULYANA MUÑOZ ACUÑA AU - NELSON FREITAS FERNANDES AU - SOMSUNDARAM CHETTIAR AU - PUI-KAI LI AU - ESPERANZA CARCACHE DE BLANCO Y1 - 2017/06/01 UR - http://ar.iiarjournals.org/content/37/6/2839.abstract N2 - 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. ER -