From Nature to Synthesis and Vice Versa: Costic Acid Analogs with Acaricidal Activity Against the Bee Parasite Varroa destructor

TL;DR

This study explores natural and synthetic compounds from Inula helenium that show acaricidal activity against the bee parasite Varroa destructor.

Contribution

The paper introduces new synthetic analogs of costic acid with acaricidal activity and identifies key pharmacophore groups.

Findings

Natural eudesmanolides from Inula helenium showed strong antioxidant activity in the methanolic extract.

Synthetic analogs of costic acid demonstrated acaricidal activity against Varroa destructor.

Structure–activity relationship studies identified important pharmacophore groups for acaricidal activity.

Abstract

The species Inula helenium belongs to the genus Inula (Asteraceae) and exhibits antibacterial and anti-inflammatory properties. It is used in respiratory and skin diseases. Its bioactivity is attributed to its eudesmanolide components, mainly to alantolactone and isoalantolactone. These components were isolated in high purity from the plant’s dried roots, either via multiple column chromatography separations or via repeated recrystallization. Two more eudesmanolides structurally similar to their parent compounds were isolated, namely 11,13-dihydro-alantolactone and 11,13-dihydro-isoalantolactone. The secondary metabolites and their derivatives were characterized in detail, for the first time, via NMR spectroscopy, GC-MS, and HRMS. Synthetic modification of the natural component structure was considered necessary for structure–activity relationship studies and biological tests. Thus, each compound was converted to its nitrile and then to the corresponding acid, or to its azide derivative and then corresponding amine. Antioxidant studies were conducted on the parent compounds, their derivatives, and the methanolic and hexane plant extracts using the DPPH radical method. The study revealed a strong antioxidant capacity of the methanolic extract. Acaricidal studies of both natural products and synthetic analogs against Varroa destructor and the comparison of their activity with the parent natural product costic acid, as well as one of its synthetic congeners, indicated that the “from nature to synthesis and vice versa” approach led to active compounds as well as to meaningful conclusions regarding the “pharmacophore” groups in the structural framework of the acaricides.

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