Rare 2,3-Naphthalides and Anti-Proliferative Hirsutinolides from Vernonia amygdalina as Dual Inhibitors of Progesterone and Estrogen Receptors: Integrated In-vitro and In-silico Approaches

Aboelmagd, Mohamed; Elgahamy, Abdelhalim Adel; AbdEl-Razek, Mohamed H

doi:10.21608/ejchem.2024.336529.10827

Rare 2,3-Naphthalides and Anti-Proliferative Hirsutinolides from Vernonia amygdalina as Dual Inhibitors of Progesterone and Estrogen Receptors: Integrated In-vitro and In-silico Approaches

Document Type : Original Article

Authors

¹ researcher at pharmacognosy department the national research center

² Chemistry of Natural and Microbial Products Department, National Research Centre

³ Institute of Pharmaceutical Industries Research, Chemistry of Natural Compounds Department, National Research Center, , 33 El-Buhouth St., Dokki, Giza 12622, Cairo, Egypt.

10.21608/ejchem.2024.336529.10827

Abstract

Two unusual 2,3-naphthalides (1 & 2) characterized as 3-hydroxymethyl-2-naphthoic acid lactones, have been documented for the first time from natural sources, alongside three previously identified sesquiterpene lactones hirsutinolide-type (3-5) which were extracted from the chloroform partition of a methanol extract of Vernonia amygdalina Dil. aerial parts. The structural elucidation was accomplished through 1D and 2D NMR spectroscopic analysis and comparing the results with the documented literature data. In the in-vitro anticancer study against MCF-7 cancer cell line, (1&2) exhibited weak cytotoxic properties, while the metabolites 3, 4, and 5 revealed pronounced inhibitory potency with IC50 values of 16.9, 18.8, and 17.6 μg/mL, respectively, which is comparable to the IC50 value of colchicine at 12.2 μg/mL.
Hirsutinolides (3, 4, and 5) are documented for the first time from the plant of V. amygdalina. A tentative structure-activity relationship for hirsutinolides 3–5's anti-proliferative properties is examined. To predict the potential interactions between the hirsutinolides (3, 4, and 5) and the estrogen receptor (ER) as well as the progesterone receptor (PGR), the in-silico studies were assessed. Additionally, the Molinspiration tool is applied for the prediction of the bioactivity scores and the Drug-like properties.

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