Delving into the Latest Updates on Terpinen-4-ol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target-

Action-

Mechanism-

Therapeutic Areas

Infectious DiseasesEye DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

BlepharitisInfestation by DemodexUnspecified blepharoconjunctivitis

Originator Organization

Tissue Technologies, Inc.

Active Organization-

Inactive Organization

BioTissue Holdings, Inc.

License Organization-

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

Login to view timeline

Background:SARS-CoV-2's remarkable capacity for genetic mutation enables it to swiftly adapt to environmental changes, influencing critical attributes, such as antigenicity and transmissibility. Thus, multi-target inhibitors capable of effectively combating various viral mutants concurrently are of great interest.Objective:This study aimed to investigate natural compounds that could unitedly inhibit spike glycoproteins of various Omicron mutants. Implementation of various in silico approaches allows us to scan a library of compounds against a variety of mutants in order to find the ones that would inhibit the viral entry disregard of occurred mutations.Methods:An extensive analysis of relevant literature was conducted to compile a library of chemical compounds sourced from citrus essential oils. Ten homology models representing mutants of the Omicron variant were generated, including the latest 23F clade (EG.5.1), and the compound library was screened against them. Subsequently, employing comprehensive molecular docking and molecular dynamics simulations, we successfully identified promising compounds that exhibited sufficient binding efficacy towards the receptor binding domains (RBDs) of the mutant viral strains. The scoring of ligands was based on their average potency against all models generated herein, in addition to a reference Omicron RBD structure. Furthermore, the toxicity profile of the highest-scoring compounds was predicted.Results:Out of ten built homology models, seven were successfully validated and showed to be reliable for in silico studies. Three models of clades 22C, 22D, and 22E had major deviations in their secondary structure and needed further refinement. Notably, through a 100 nanosecond molecular dynamics simulation, terpinen-4-ol emerged as a potent inhibitor of the Omicron SARS-CoV-2 RBD from the 21K clade (BA.1); however, it did not show high stability in complexes with other mutants. This suggests the need for the utilization of a larger library of chemical compounds as potential inhibitors.Conclusion:The outcomes of this investigation hold significant potential for the utilization of a homology modeling approach for the prediction of RBD’s secondary structure based on its sequence when the 3D structure of a mutated protein is not available. This opens the opportunities for further advancing the drug discovery process, offering novel avenues for the development of multifunctional, non-toxic natural medications.

01 May 2025·Current Microbiology

Synergistic Antimicrobial Effects of Melaleuca alternifolia Essential Oil and Kojic Acid Combinations

Article

Author: Kırcı, Damla ; Demirci, Betül ; Demirci, Fatih ; Batur, Özge Özşen

Melaleuca alternifolia (tea tree) essential oil (TTO) is widely recognized for its anti-inflammatory and antimicrobial properties, attributed primarily to its major constituent, terpinen-4-ol. Kojic acid, a well-established compound used mainly in cosmetic formulations, exhibits potent antioxidant and broad-spectrum antimicrobial activities. In this study, the antimicrobial potential of commercial Pharmacopoeia-grade TTO was evaluated with kojic acid and terpinen-4-ol combinations. The quality of TTO was confirmed through GC-FID and GC/MS analyses, where terpinen-4-ol was the major component (44.4%). In vitro antimicrobial assays were performed against human pathogens including Candida utilis, Candida albicans, Candida krusei, Candida tropicalis, Candida parapsilosis, Escherichia coli, and Salmonella Typhimurium. Notably, all tested samples demonstrated activity against S. Typhimurium. Kojic acid combined with TTO showed a synergistic effect, with a fractional inhibitory concentration index (FICI) of 0.266, while the combination of kojic acid and terpinen-4-ol showed an even stronger synergistic effect (FICI: 0.039). The combination of TTO and terpinen-4-ol produced an additive effect (FICI: 0.508). To the best of our knowledge, this study is the first to demonstrate the combined effectiveness of TTO and kojic acid against S. Typhimurium. The synergistic activity observed with the combination of terpinen-4-ol and kojic acid highlights its potential as an antimicrobial for a therapeutic strategy, after safety evaluations.

12 Mar 2025·Journal of Agricultural and Food Chemistry

Functional Characterization of an Antenna-Biased Odorant Receptor AaOr96 Involved in Tea Tree Oil Repellency Against Aedes aegypti

Article

Author: Chen, Mengli ; Chen, Guoxing ; Chen, Peitong ; Yan, Ru ; Song, Tiefeng ; Tian, Chunxia ; Xu, Zhanyi ; Zhu, Guonian ; Qian, Jiali ; Jin, Yongfeng

Numerous essential oils have been well acknowledged as eco-friendly alternatives to combat insect pests due to synthetic insecticide-induced pest resistance and environment pollution. As a highly commercial essential oil, tea tree oil exhibits excellent insecticidal and repellent activities. However, the molecular mechanism of the olfactory system mediating the tea tree oil-induced repellency against insect pests remains unknown. In our study, mosquito was used as a suitable model to examine the molecular mechanism of tea tree oil-induced repellency against insect pests. The results showed that tea tree oil exhibited excellent spatial and oviposition repellency against Aedes aegypti adults and outstanding repellency against larvae, which were conferred by the main constituent terpinen-4-ol. The reduced repellency in the Orco^-/- mutant strain revealed that tea tree oil-induced repellency against mosquitoes was dependent on odorant receptor(s). Moreover, we identified one antenna-biased odorant receptor, AaOr96, that was involved in detecting constituents of tea tree oil to elicit repellency, and the predicted protein-ligand complex indicated that AaOr96 interacted with terpinen-4-ol via van der Waals forces from five key residues. Finally, knocking out AaOr96 resulted in a reduced spatial repellency against A. aegypti by tea tree oil and terpinen-4-ol, and a reduced oviposition repellency by terpinen-4-ol, but not by tea tree oil. Our study not only reveals that tea tree oil has great potential in pest management but also provides more insights into the molecular basis of repellency of essential oils.

100 Deals associated with Terpinen-4-ol

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Unspecified blepharoconjunctivitis	Phase 1	United States	BioTissue Holdings, Inc.	28 Feb 2014
Blepharitis	Phase 1	United States	BioTissue Holdings, Inc.	01 Feb 2014
Infestation by Demodex	Phase 1	United States	BioTissue Holdings, Inc.	01 Feb 2014

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01647217 (DBTS, CTgov)	Phase 1	Infestation by Demodex \| Blepharitis	17	Terpinen-4-ol (Terpinen-4-ol Treatment Arm)	wekzrlmvdg(szptbfqmxp) = dfyylxanfz tdwzhrjljs (nanbpetlah, jofumdbdeo - isirgdweoc) View more	-	26 Jul 2017
NCT01647217 (DBTS, CTgov)	Phase 1	Infestation by Demodex \| Blepharitis	17	Placebo (Placepo Pads Contol Arm)	wekzrlmvdg(szptbfqmxp) = ysvdrpoxxv tdwzhrjljs (nanbpetlah, uzrpccacjo - wfnpsvflxx) View more	-	26 Jul 2017
UEGW2015	Not Applicable	Colorectal Cancer	-	Terpinen-4-ol	xiriugtgct(sdzugcfilg) = ovhjhskzys dpcbiyfvcu (aqirkbyofl )	Positive	01 Oct 2015