New derivatives of a natural nordentatin

Abstract

New derivatives were obtained from natural nordentatin (1) previously isolated from the methanol fraction of Clausena excavata by an acylation method. Herein, we report ten new pyranocoumarin derivatives 1a–1j. Their structures were elucidated based on UV-vis, FT-IR, NMR, and DART-MS data. The α-glucosidase inhibition and anticancer activities of nordentatin (1) and its derivatives were also evaluated. The α-glucosidase inhibition assay exhibited that the derivatives 1b, 1d, 1e, 1f, 1h, 1i, and 1j possess higher inhibitory activity for α-glucosidase with IC50 values of 1.54, 9.05, 4.87, 20.25, 12.34, 5.67, and 2.43 mM, whereas acarbose was used as the positive control, IC50 = 7.57 mM. All derivatives exhibited a weak cytotoxicity against a cervical cancer (HeLa) cell line with the IC50 between 0.25 and 1.25 mM. They also showed moderate to low growth inhibition of a breast cancer (T47D) cell line with IC50 values between 0.043 and 1.5 mM, but their activity was lower than that of the parent compound, nordentatin (1) (IC50 = 0.041 mM).

Structure-based approach: molecular insight of pyranocumarins against α-glucosidase through computational studies

“…In particular, E vdW shows a significant energy contribution (>−60.00 kcal mol −1 ) to the interaction energy of pyranocoumarins against α-glucosidase. Overall, the grid score analysis showed an inhibitory activity (IC 50 ) which is similar to the results of the in vitro test that we previously reported, 14 PC1 > PC3 > PC2 > AC1. We assume that the contribution of E vdW has a significant contributor to the interaction energy between pyranocumarins and α-glucosidase, thermodynamically.…”

“…Meanwhile, the pyranocoumarin derivatives (PC1, PC2, and PC3) modeled in this study have been successfully synthesized and characterized by previous studies. 14 For the preparation of pyranocoumarins, the electrostatic potential (ESP) charges were calculated using semiempirical quantum parametric method-3 (SQM-PM3) via Gaussian 16 package. 18 Additionally, the addition of hydrogen atoms, AMBER FF14SB force field, and AM1-BCC aims to calculate missing parameters, such as bonded, non-bonded, and charge.…”

“…Previous studies showed that coumarin derivatives played a promising role in inhibiting the activity of aglucosidase. [12][13][14] One of them is nordentatin, where nordentatin is the majority secondary metabolite compound of Clausena excavata. This compound was modied using a semi-synthetic method into ester derivatives to develop anti-diabetic candidates.…”

“…This compound was modified using a semi-synthetic method into ester derivatives to develop anti-diabetic candidates. 14 The availability of nordentatin from natural products has advantages in anti-diabetic development. Therefore, the study of structural modification becomes crucial in developing anti-diabetic candidates.…”

“…Some of them, namely PC1 (IC 50 : 1.54 mM), PC2 (IC 50 : 4.87 mM), and PC3 (IC 50 : 2.43 mM). 14 Based on the report, three semi-synthetic pyranocoumarin derivatives ( Fig. 1 ) are selected as the main focus in this study for further study of the mechanism of α-glucosidase inhibition at the molecular level.…”