title: Targeting HER-2 over expressed breast cancer cells with 2-cyclohexyl-N-[(Z)-(substituted phenyl/furan-2-yl/thiophene-2-yl)methylidene]hydrazinecarbothioamide.
abstract: Cyclohexyl thiosemicarbazone derivatives (C1-14) were synthesized, characterized and evaluated against HER-2 over expressed breast cancer cells. The synthesized compounds were screened in vitro against four breast cancer cell lines; SKBr-3, MCF-7, MDA-MB-468 and MDA-MB-231. All the compounds showed activity against HER-2 over expressed SKBr-3 cells with (IC₅₀ = 25.6 ± 0.07 μM-61.6 ± 0.4 μM). The most active compounds inhibit ALDH⁺ breast cancer stem cells more effectively than the cancer stem cells specific agent Salinomycin. Immunohistochemistry staining also confirmed that these compounds inhibit the expression of HER-2 on SKBr-3 cells. Compound C2 significantly inhibited the cell migration and cell adhesion of breast cancer cell lines. Compound C2 was found to most active compound of this series targeting HER-2 over expressed breast cancer cells.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. mashooqbhat@rediffmail.com
authors.forename: Mashooq Ahmad
authors.initials: MA
authors.lastname: Bhat
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
authors.forename: Azmat Ali
authors.initials: AA
authors.lastname: Khan
authors.forename: Nouf
authors.initials: N
authors.lastname: Al-Harbi
authors.forename: P S
authors.initials: PS
authors.lastname: Manogaran
authors.forename: Amer M
authors.initials: AM
authors.lastname: Alanazi
authors.forename: Hoong-Kun
authors.initials: HK
authors.lastname: Fun
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Al-Omar
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013882:Thiosemicarbazones / Q000008:administration & dosage / Q000138:chemical synthesis*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D013882:Thiosemicarbazones; C508053:ERBB2 protein, human