Lead Optimization of 2-Cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides for Targeting the HER-2 Overexpressed Breast Cancer Cell Line SKBr-3
Mashooq A. Bhat,
Abdullah Al-Dhfyan,
Ahmed M. Naglah,
Azmat Ali Khan,
Mohamed A. Al-Omar
Affiliations
Mashooq A. Bhat
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
Abdullah Al-Dhfyan
Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, P. O. Box 3354, Riyadh 11211, Saudi Arabia
Ahmed M. Naglah
Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Azmat Ali Khan
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
Mohamed A. Al-Omar
Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1–18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC50 = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation.
