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Synthesis, Molecular Docking, and Cytotoxic Evaluation of Some Novel 1H-Pyrazole Derivatives from Pentoxifylline
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| Author:
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JESSICA SHLIMOON HANNA, AYAD KAREEM KHAN, HAYDER JAFER ESSA
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| Abstract:
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New Methylxanthine-based derivatives were designed synthesized and primarily screened for their cytotoxic activity against human A549 (lung) cancer cell line. Pentoxifylline (PTX) is a synthetic Methylxanthine derivative act as a nonselective phosphodiesterase inhibitor (PDEI). The new derivatives were designed by incorporating pyrazoline pharmacophore into Pentoxifylline. The Claisen-Schmidt condensation reaction were used to synthesize intermediates chalcone derivatives [1, 2, 3, 4, and 5]. The pyrazole derivatives [1a, and 1b] in the second step synthesized and all compounds were characterized by melting points, Rf values, and confirmed by FT-IR and 1H-NMR spectroscopy. The computational methods done before synthesis including ADME studies were performed using the SwissADME server to predict the pharmacokinetics of the designed compounds. The results showed that all compounds expected passively and highly absorbed from The GIT. Besides, all synthesized compounds satisfied the Rule of five (RO5) except compound [1b]. The designed compounds checked for their selectivity towards EGFR by using GOLD suite software. All the designed compounds exhibit good binding energies with receptor active pocket and having promising activity with these proteins. The IC50 values of the tested compounds exhibit that compounds [3, 4, 5, and 1b] have potent to moderate cytotoxic activity. Among them, the most potent was compound [5] with an IC50 value of 11.44 µM compared to the standard drug Erlotinib with an IC50 value of 25.23 µM. while the percentage of cell death was 81.21% for compound [5]; appear to be slightly lower than erlotinib with 82.40% of cell death.
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| Keyword:
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Pentoxifylline, Pyrazole, Docking Study, ADME Evaluation.
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2020.12.02.424
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| Download:
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