Essential oils, those liquids redolent of lavender, peppermint, and other plants, have seldom been taken seriously as therapeutics. The seeming lack of respect, a research team in Belgium suggests, has less to do with scientific snobbery than it does with practical difficulties in the laboratory. Specifically, essential oil components have been deemed too volatile and too hydrophobic to be easily processed by today’s high-throughput screening techniques.

Essential oils, however, may be overdue for a closer look. The plant metabolites they contain are readily obtained by dry or steam distillation, or by citrus peel pressing. And these compounds possess physicochemical properties that are, in the estimation of the Belgian scientists, compatible with “current-day requirements of medicinal chemistry for good drug candidates.”

The scientists, led by Prof. Patrick Van Dijck (VIB-KU Leuven Center for Microbiology) and Prof. Walter Luyten (KU Leuven Department of Biology), published their findings February 18 in Science Advances, in an article entitled, “Striking essential oil: tapping into a largely unexplored source for drug discovery.” The article describes how the drug discovery parameters (DDPs) of essential oil compounds (EOCs) obtained from a set of commercially available essential oils were calculated, analyzed, and summarized.

After this work was accomplished, the lead- and drug-likeness of the EOCs were evaluated using all the drug discovery filters (DDFs) available in JChem (for Office) from ChemAxon, a widely accepted cheminformatics software package in drug discovery. Additionally, the Rule of Three (Ro3) DDF was used to test if some EOCs would be potential candidates for fragment-based drug discovery

“Here we evaluate selected physicochemical parameters, used in conventional drug discovery, of essential oil components present in a range of commercially available essential oils,” the article’s authors wrote. “We show that, contrary to generally held belief, most essential oil components … offer attractive opportunities for lead optimization or even fragment-based drug discovery. Because their therapeutic potential is still under-scrutinized, we propose that this be explored more vigorously with present-day methods.”

The analysis established a key metric: u-cmc, or unique core molecular constitution. Then it compared umcEOCs, the unique Core Molecular Constitution of EOCs to u-cmcADs, the unique Core Molecular Constitution of Approved Drugs. (The “cmc” of a molecule describes, among other things, its chemical formula, connectivity, and hydrogen positions. The “u” indicates that overlaps in the constitution of different compounds have been eliminated.)

The articles authors noted that EOCs have unusual properties. “However, when these properties are benchmarked against various measures of drug-likeness,” they continued, “most EOCs pass with flying colors. For example, all u-cmcEOCs passed the Ro5 when only three of the four criteria had to be met. In addition, almost 94% of the EOCs passed at least any four out of six standard DDFs.”

The current study is rooted in the observation that in the past decades, drug discovery has mainly shifted to high-throughput screening of large, synthetically produced chemical libraries, while natural product drug research has diminished. However, recent technical developments combined with restrictions on the use of chemicals led to a renewed interest in natural product drug discovery.

Some of the new methods to study essential oils and their components were developed in the laboratory of Prof. Van Dijck under the coordination of Dr. Adam Feyaerts, mainly with the aim of finding new antimicrobials, for example antifungal drugs.

“Nowadays, a relatively large number of essential oils and their components are already available as dietary supplements, but only a few have made the transition to drugs,” said Feyaerts. “As most technical barriers were removed, I wondered whether avoiding essential oils and their components in drug discovery was still justified. So, we evaluated certain parameters used in conventional drug discovery for more than 600 essential oil components to assess their potential as drug candidates.”

“The discovery and development of a new drug takes a long time and is very expensive, not in the least because so many initial candidates turn out not to be suitable,” noted Luyten. “In other words, the earlier in the drug discovery process non-promising molecules can be eliminated, the better. Many candidate drug molecules fail when they are tested in animals.”

Could EOCs represent a treasure trove of potential drugs? Fortunately, in silico drug discovery filters have been developed that can predict drug disposition based on combinations of specific calculated parameters, which reduced the rate at which potential drugs failed later in the drug development pipeline. This study shows that essential oil components can be assessed using the filters implemented by the pharmaceutical industry.

“EOCs,” the authors of the current study concluded, “are promising (sources of) new drugs and deserve more attention in the future. EOCs also have unique properties that might be useful for some therapeutic applications.” They noted that conditions that could benefit from EOCs include lung or airway diseases and diseases of the central nervous system.

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