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- ISSN: 1570-1786
- E-ISSN: 1875-6255
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Synthesis and Anticancer Activity Evaluation of N-(3,4,5-Trimethoxycinnamoyl)anthranilic Acid Derivatives
- Source: Letters in Organic Chemistry, Volume 22, Issue 7, Jul 2025, p. 580 - 590
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- 03 Oct 2024
- 08 Nov 2024
- 23 Jan 2025
Abstract
There is an urgent need to search for more efficient, better-tolerated anticancer drugs. Tranilast, a synthetic analog of tryptophan metabolite, has been shown to inhibit the growth of various cancer cells. In our previous study, the tranilast analog TRA01 [N-(3,4,5-trimethoxycinnamoyl) anthranilic acid] was identified as a promising agent against the proliferation of MCF-7 and HepG2 cell lines along with good binding affinity on the transforming growth factor beta 1 (TGFβ1) target. To further explore the structure-activity relationship, a series of N-(3,4,5-trimethoxycinnamoyl) anthranilic acid derivatives 5a–i were successfully synthesized via a two-step synthetic procedure based on N-acylation and Knoevenagel-Doebner reactions and their structures were determined using 1H-NMR, 13C-NMR, and MS spectra. The derivatives (5a–i) were evaluated for in vitro activity using MTT assay and in silico docking on TGFβ1 target by AutoDockTools–1.5.6 software. The bioactivity results of 5a–i showed 12.30–27.04% and 19.13–46.23% inhibition on proliferation of MCF-7 and HepG2 cell lines at 100 µM concentration, respectively, with the fluorinated derivatives (5a and 5e) possessing the strongest inhibitory activities. The molecular docking also found the best binding affinity of 5a (-8.70 Kcal/mol) and 5e (-8.71 Kcal/mol) on the TGFβ1 target. The SAR result revealed that substituents on the benzene ring of anthranilic acid were not favored for anticancer activity. Although these derivatives exhibited weak anticancer properties, the good binding affinity to the TGFβ1 target suggested certain potential of this scaffold for further study on this target.
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