دورية
Synthesis, anticancer evaluation and molecular docking studies of methotrexate’s novel Schiff base derivatives against malignant glioma cell lines
| العنوان: | Synthesis, anticancer evaluation and molecular docking studies of methotrexate’s novel Schiff base derivatives against malignant glioma cell lines |
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| المؤلفون: | Nemat, Aifa, Khan, Ishaq N., Kalsoom, Saima, Malik, Shoaib Ahmad, Ayub, Shahid, Adnan, Fazal, Kamal, Mohammad Amjad, Iqbal, Mudassir |
| المصدر: | Journal of Biomolecular Structure and Dynamics; May 2022, Vol. 40 Issue: 7 p2865-2877, 13p |
| مستخلص: | AbstractRecent years have witnessed advancement in cancer research that has led to the development of improved cytotoxic therapies with reduced side effects. Methotrexate (MTX) is a commonly used anticancer drug having robust activity, but with serious side effects. Several derivatives of MTX have been reported by modification at different sites to reduce its side effects and enhance efficacy. The current work describes the development of active MTX Schiff base derivatives by treating MTX with several aldehydes viz 2-chlorobenzaldehyde, 3-nitrobenzaldehyde, 5-chloro-2-hydroxybenz-aldehyde, 2-hydroxy-5-nitrobenzaldehyde, 2-thiocarboxyaldehyde, trans-2-pentenal and glutaraldehyde. Newly synthesized derivatives were evaluated for their anticancer potential against human malignant glioma U87 (MG-U87) cell lines at different concentrations of 200 μM, 100 μM, 50 μM, 25 μM, 12.5 μm, 6.25 μm and 0 μM. MTX derivatives with 2-Chlorobenzaldehyde (IC50∼100 μM), 2-Thiocarboxyaldehyde (IC50<200 μM) and 2- Pentenal (IC50∼250 μM) showed much better activity at 100 µM compared to 400 µM concentration of MTX. Molecular docking studies were performed that showed a good correlation with the results obtained from in vitroexperiments. The excellent agreement between molecular modeling and growth inhibition assay shows that the binding mode hypothesis is justly close to the experimentally biological values, therefore, may prove helpful for further lead optimization and clinical trials.Communicated by Ramaswamy H. Sarma |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 07391102 15380254 |
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| DOI: | 10.1080/07391102.2020.1844053 |