Biological approach of anticancer activity of new benzimidazole derivatives |
| |
| Affiliation: | 1. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia;2. New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar 301030, Rajasthan, India;3. New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar 301030, Rajasthan, India;4. School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia;5. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States;1. Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India;2. Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India;1. Department of Chemistry, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia;2. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;3. Cancer Pharmacology Division, Indian Institute of Integrative Medicine, CSIR, Canal Road, Jammu 180001, India;4. Department of Ag. Microbiology, Faculty of Ag. Sciences, Aligarh Muslim University, Aligarh, India;5. Institute of General and Ecological Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland;1. Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;2. IICT – RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;3. Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Applied Sciences, RMIT University, Melbourne 3000, Australia;4. Health Innovations Research Institute, RMIT University, Melbourne 3083, Australia;5. Centre for Advanced Materials and Industrial Chemistry, RMIT University, Melbourne 3000, Australia |
| |
| Abstract: | BackgroundA series of new benzimidazole derivatives, earlier synthesized, was tested in vitro as new bioreductive prodrugs with the potential anticancer activity. Their effect on the DNA destruction and growth inhibition into selected tumor cell lines at normoxia and hypoxia conditions was determined.MethodsThe human lung adenocarcinoma A549 cell line was used to determine the anticancer activity of the analyzed compounds by using WST-1 assay. The apoptosis test (caspase 3/7 assay) was used to define the cytotoxic way of tumor cells death. Additionally test In situ DNA Damage Assay Kit was applied to recognize the DNA destruction.ResultsFour of the examined compounds (1, 3, 7, 9) show a very good antiproliferative effect and three of them are specific for hypoxia conditions (2, 4, 8).ConclusionCompound 8 is the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/normoxia cytotoxic coefficient of compound 8 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) – reference substance in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). The screening test of the caspase-dependent apoptosis proved that the exposure of compounds 1–2 and 7–8 against A549 cells for a 48 h promote apoptotic cell death. Additionally, the test of the DNA damage established that compounds 1, 2, 7, 8 are specific agents for the hypoxia-selective cytotoxicity of nitrobenzimidazoles [6], [26]. |
| |
| Keywords: | Anticancer activity Benzmidazole Bioreductive prodrugs Hypoxia Nitrobenzimidazole |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
