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7157641 
Journal Article 
Synthesis, anticancer evaluation and molecular docking studies of methotrexate's novel Schiff base derivatives against malignant glioma cell lines 
Nemat, A; Khan, IN; Kalsoom, S; Malik, SA; Ayub, S; Adnan, F; Kamal, MA; Iqbal, M; , 
2020 
Yes 
Journal of Biomolecular Structure & Dynamics
ISSN: 0739-1102 
TAYLOR & FRANCIS INC 
PHILADELPHIA 
33183168 
WOS:000588820200001 
Recent 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 mu M, 100 mu M, 50 mu M, 25 mu M, 12.5 mu m, 6.25 mu m and 0 mu M. MTX derivatives with 2-Chlorobenzaldehyde (IC50 similar to 100 mu M), 2-Thiocarboxyaldehyde (IC50 <200 mu M) and 2- Pentenal (IC50 similar to 250 mu M) showed much better activity at 100 mu M compared to 400 mu M concentration of MTX. Molecular docking studies were performed that showed a good correlation with the results obtained from in vitro experiments. 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