Synthesis and activity of N-(o-tolyl)caffeamide and N-(o-tolyl)-p-coumaramide against P388 leukemia murine cells

Abstract

Ester derivatives of p-hydroxycinnamic compounds have high anticancer activity. However, the ester compounds usually easier to be decomposed than their amide derivates, so the ester compounds have a low potential to be applied as anticancer. In this research, the amide derivatives of caffeic and p-coumaric acids have been synthesized using o-tolylamine to give trans-N-(o-tolyl)caffeamide (5a) and trans-N-(o-tolyl)-p-coumaramide (5b), respectively. The products were characterized by FT-IR, 13C-NMR, and 1H-NMR methods. In the FT-IR spectrum, compound 5a showed absorption bands of N-H bond at 3236.55 cm−1 and 1533.41 cm−1 as stretching and bending vibrations, respectively; and compound 5b had absorption bands at 3267.41 cm−1 and 1527.82 cm−1. In the 13C-NMR spectrum, compound 5a gave 15 of peaks that representing 16 of carbons, and compound 5b gave 14 of peaks that were also representing 16 of carbons. In the 1H-NMR spectrum, the peak of N-H of compound 5a and compound 5b appeared at 8.57 ppm and 8.87 ppm, respectively. Activity assay results of both compounds against P388 leukemia murine cells indicated that both compounds have a high potential as anticancer, especially compound 5a. The compound 5a was more active than the analogous compounds which the previous synthezised.

Novel hydroxycinnamamide from morpholine and pyrrolidine: Synthesis, characterization, docking study, and anticancer activity against P388 leukemia murine cells

“…As shown in the docking study, it is due to the presence of an intramolecular hydrogen bond between the adjacent hydroxyl groups, which can stabilize the structure after releasing hydrogen radicals. This result is consistent with the previous report related to the comparison of anticancer activity between caffeamide and p-coumaramide (Firdaus et al, 2019). Meanwhile, compared to the activity of p-coumaramide that was isolated from Kleinhovia Hospita L. (IC 50 of 44.00 μg/ml) (Firdaus et al, 2014) and N-feruloyl morpholine which previously synthesized (IC 50 of 46.67) (Firdaus et al, 2017), compound 6a was considerably more active.…”

Synthesis of 3-(3,4-diacetoxyphenyl)acrylic acid and 4-(oxo-3-(piperidin-1-yl)pro-1-en-1-yl)-1,2-phenylendiacetate from 3-(3,4-dihydroxyphenyl)acrylic acid and their toxicity test by Brine Shrimp Lethality Test method

“…The absorption band is also supported by the absorption band at wavenumbers 1213.23 cm -1 and 1114.86 cm -1 from C-O. The absorption bands at 2835.36-2981.95 cm -1 and 1431.18 and 1373.32 cm -1 originated from the CH3 group (Firdaus et al, 2019). All absorption bands correspond to the structure of compound 1b shown in Figure 6.…”

“…), 1602.85 dan 1508.41 cm -1 (C=C Ar), 2943.37 dan 2858.51 cm -1 (C-H sat. ), 1369.46 dan 1444.68 cm -1 (methyl) (Firdaus et al, 2019). This explanation is in accordance with the structure of compound 3c in Figure 6.…”

“…One method used to convert acid groups into amide groups is through an indirect conversion method with four stages of synthesis, namely the acetylation, chlorination, amidation and deacetylation stages (Firdaus et al, 2018). This method has successfully synthesized amide derivatives from hydroxycinnamic acid such as phenethyl trans-3-(4-hydroxy-3-methoxyphenyl) acrylate, trans-3-(4-hydroxy-3-methoxyphenyl)-N-phenethyl acrylamide, N-(o-tolyl) caffe amide, and N-(o-tolyl) p-coumaramide which have bioactivity to murine leukemia P-388 cells with IC50 values of 10.79 μg/mL, 29.14 μg/mL, 0.91 μg/mL and 16.97 μg/mL, respectively (Firdaus et al, 2019). This method has been used in this research to obtain compound 1 and compound 3.…”

Synthesis of <i>N</i>-phenethyl-<i>p</i>-methoxycinnamamide and <i>N</i>-morpholinyl-<i>p</i>-methoxycinnamamide, <i>In Vitro</i> and <i>In Silico</i> Study as α-Glucosidase Inhibitor

“…The two most abundant compounds in the aromatic ginger essential oil were trans-ethyl-pmethoxycinnamate and trans-ethyl cinnamate [1][2]5]. Ethyl-p-methoxycinnamate and its derivatives had many benefits, including as anticancer [6][7][8], anti-inflammatory [9][10], anti-tuberculosis [11], anti-neoplastic [12], antimicrobe [13], and antidiabetic [14] agents. The study of K. galanga L. extract as an antidiabetic using the Gavage method every day for one month found that diabetic rats before and after treatment with K. galanga L. extract showed a significant difference in reducing the amount of blood glucose [15].…”