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
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...
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| Format: | Article |
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MDPI AG
2015-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/10/18246 |
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| author | Mashooq A. Bhat Abdullah Al-Dhfyan Ahmed M. Naglah Azmat Ali Khan Mohamed A. Al-Omar |
| author_facet | Mashooq A. Bhat Abdullah Al-Dhfyan Ahmed M. Naglah Azmat Ali Khan Mohamed A. Al-Omar |
| author_sort | Mashooq A. Bhat |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:33:15Z |
| format | Article |
| id | doaj.art-168aadf10f8c4464817de8c23884f852 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T21:33:15Z |
| publishDate | 2015-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-168aadf10f8c4464817de8c23884f8522022-12-22T03:15:58ZengMDPI AGMolecules1420-30492015-10-012010182461826310.3390/molecules201018246molecules201018246Lead Optimization of 2-Cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides for Targeting the HER-2 Overexpressed Breast Cancer Cell Line SKBr-3Mashooq A. Bhat0Abdullah Al-Dhfyan1Ahmed M. Naglah2Azmat Ali Khan3Mohamed A. Al-Omar4Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaStem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, P. O. Box 3354, Riyadh 11211, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaLead 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.http://www.mdpi.com/1420-3049/20/10/18246thiosemicarbazonesHER-2SKBr-3 cellsBT-474 cellscancer stem cells |
| spellingShingle | Mashooq A. Bhat Abdullah Al-Dhfyan Ahmed M. Naglah Azmat Ali Khan Mohamed A. Al-Omar 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 Molecules thiosemicarbazones HER-2 SKBr-3 cells BT-474 cells cancer stem cells |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | thiosemicarbazones HER-2 SKBr-3 cells BT-474 cells cancer stem cells |
| url | http://www.mdpi.com/1420-3049/20/10/18246 |
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