Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking
Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides (2−13) were synthesized and character...
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Elsevier
2025-09-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625005995 |
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| author | Basharat Ali Muhammad Riaz Ajmal Khan Nadir Rasheed Muhammad Masood Ali Iftikhar Amir Faisal Sobia Ahsan Halim Jalal Uddin Afnan Jan Ahmed Al-Harrasi |
| author_facet | Basharat Ali Muhammad Riaz Ajmal Khan Nadir Rasheed Muhammad Masood Ali Iftikhar Amir Faisal Sobia Ahsan Halim Jalal Uddin Afnan Jan Ahmed Al-Harrasi |
| author_sort | Basharat Ali |
| collection | DOAJ |
| description | Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides (2−13) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance (HNMR, and 13C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives (2–13) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds (2, 4, 11, and 12) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide (11) as the most potent compound with IC50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents. |
| format | Article |
| id | doaj-art-d0e27678c6a6469fa9d3c30cd90d8ef7 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-d0e27678c6a6469fa9d3c30cd90d8ef72025-08-22T04:56:15ZengElsevierResults in Chemistry2211-71562025-09-011710261610.1016/j.rechem.2025.102616Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular dockingBasharat Ali0Muhammad Riaz1Ajmal Khan2Nadir Rasheed3Muhammad Masood4Ali Iftikhar5Amir Faisal6Sobia Ahsan Halim7Jalal Uddin8Afnan Jan9Ahmed Al-Harrasi10Sulaiman Bin Abdullah Aba Al-Khail – Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad, Pakistan; Department of Chemistry, University of Baltistan, Skardu, Pakistan; Corresponding author at: Sulaiman Bin Abdullah Aba Al-Khail – Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad, Pakistan.Sulaiman Bin Abdullah Aba Al-Khail – Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad, PakistanNatural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman; Department of Chemical and Biological Engineering, College of Engineering, Korea University, Seoul 02841, Republic of KoreaSulaiman Bin Abdullah Aba Al-Khail – Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad, PakistanSulaiman Bin Abdullah Aba Al-Khail – Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad, PakistanDepartment of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, PakistanDepartment of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan; Corresponding authors at: Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman.Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, OmanDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia.Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman; Corresponding authors at: Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman.Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides (2−13) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance (HNMR, and 13C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives (2–13) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds (2, 4, 11, and 12) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide (11) as the most potent compound with IC50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents.http://www.sciencedirect.com/science/article/pii/S2211715625005995SynthesisThiosemicarbazidesCarbothioamidesAnticancer activitiesMolecular dockingADMET prediction |
| spellingShingle | Basharat Ali Muhammad Riaz Ajmal Khan Nadir Rasheed Muhammad Masood Ali Iftikhar Amir Faisal Sobia Ahsan Halim Jalal Uddin Afnan Jan Ahmed Al-Harrasi Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking Results in Chemistry Synthesis Thiosemicarbazides Carbothioamides Anticancer activities Molecular docking ADMET prediction |
| title | Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking |
| title_full | Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking |
| title_fullStr | Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking |
| title_full_unstemmed | Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking |
| title_short | Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking |
| title_sort | carbothioamides as anticancer agents synthesis in vitro activity structure activity relationship evaluations and molecular docking |
| topic | Synthesis Thiosemicarbazides Carbothioamides Anticancer activities Molecular docking ADMET prediction |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625005995 |
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