Trends Sci. 2026; 23(1): 11324

Bioactive Compounds from Trentepohlia aurea as Potential Antibacterial Agents Targeting DNA Gyrase: An In Vitro and In Silico Approach

Oky Kusuma Atni, Erman Munir^* and Nursahara Pasaribu

Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan 20155, North Sumatera, Indonesia

(^*Corresponding author’s e-mail: [email protected])

Received: 19 July 2025, Revised: 12 August 2025, Accepted: 19 August 2025, Published: 30 October 2025

Abstract

The global rise of antibiotic resistance underscores the urgent need for novel antibacterial agents with new mechanisms of action. Trentepohlia aurea, a carotenoid- and phenolic-rich subaerial green alga, remains largely unexplored for its therapeutic potential. This study evaluated the antibacterial activity of its methanol extract via in vitro disc diffusion assays and investigated the interaction of its bioactive constituents with bacterial DNA gyrase subunit B (PDB ID: 6KZZ) through in silico molecular docking. The extract produced inhibition zones of 11.3 ± 0.55 mm against Staphylococcus aureus, 10.9 ± 0.21 mm against Salmonella Typhii, and 10.8 ± 0.61 mm against Streptococcus mutans, indicating moderate antibacterial activity. GC-MS profiling identified 26 compounds, with Aphthosin exhibiting the strongest predicted gyrase-binding affinity (–7.4 kcal/mol), surpassing a native ligand. ADME-toxicity predictions suggested generally favorable pharmacokinetics with low toxicity, though some compounds displayed organ-specific risks. While MIC/MBC determinations and direct in vitro testing of individual compounds were not performed, this first report on T. aurea as a potential DNA gyrase inhibitor highlights its promise as a source of structurally diverse natural products for antibacterial drug discovery and warrants further mechanistic validation and potency optimization.

Keywords: Antibacterial, DNA gyrase, GC-MS, In silico, Molecular docking, Trentepohlia aurea

Introduction

Algae comprise a vast array of photosynthetic organisms, varying from unicellular microscopic species to large multicellular forms, encompassing both prokaryotic and eukaryotic types 1,2 . Algal organisms are prolific producers of structure ally unique and physiologically active compounds. A multitude of alleged bioactive compounds produced by these organisms as primary or secondary metabolites has attracted attention in the pharmaceutical sector 3 . Microalgal metabolism adapts to alterations in the external environment by modifying its internal conditions. Consequently, altering the cultural conditions or the availability of nutrients enhances the synthesis of specific compounds. Several research have been done to explore the products of microalgal metabolism, not only to better understand their nature, but also to look for chemicals with potential human

applications in a variety of disciplines. Extracts or metabolites from various microalgae are commonly screened to determine their biological activity. Microalgae have been recognized as abundant suppliers of numerous bio compounds with economic interest [4-6].

The family Trentepohliaceae and order Trentepohliales include Trentepohlia. The Ulvophyceae class of Chlorophyta includes this subaerial algae genus. Trentepohlia is the most abundant tropical and subtropical subaerial algae [7]. The diversity of Trentepohlia species is influenced by altitude and environmental factors, including humidity, temperature, and light intensity [8]. Trentepohlia species synthesize substantial quantities of carotenoids that provide protection against ultraviolet radiation and elevated irradiance. Their pigments give them a distinguishable yellow, orange, or red color in natural settings [9]. Important bioactive substances identified in the genus Trentepohlia include β-carotene, lutein, astaxanthin, microalgal pigments such as chlorophylls (a, b and c), phycocyanin, phycoerythrin, β-carotene, and phycobiliproteins [10]. Trentepohlia holds significant potential as a valuable resource in the pharmaceutical sector, particularly for its antimicrobial and antioxidant properties. Its bioactive compounds can be utilized to develop new antimicrobial agents to combat infections and antioxidants to protect against oxidative stress, thereby contributing to advancements in therapeutic and preventive healthcare solutions [11,12].

Schema of the PDB The DNA gyrase B complex with a 2-oxo-1,2-dihydroquinoline derivative is seen in the crystal structure of Escherichia coli at 6KZZ. One of the most important enzymes for DNA replication and transcription is DNA gyrase, which is produced by bacteria. It adds negative supercoils into DNA [13]. The 2 components of DNA gyrase, GyrA and GyrB, work together as a heterodimer. DNA cleavage and rejoining are carried out by GyrA, whereas the energy required for these processes is supplied by GyrB, which displays ATPase activity [14,15]. The GyrB subunit is targeted by many antibacterial agents due to its role in ATP hydrolysis. Competing in ATP GyrB inhibitors are made up of different chemical groups, such as coumarins, arylaminopyrimidines, ethyl ureas, tricyclic inhibitors, and pyrrolamides. They are good at killing both Gram-positive and Gram-negative bacteria [16]. The 6KZZ structure provides significant insights into the binding interactions and mechanisms of these inhibitors. Comprehending this structural information is essential for clarifying the impact of these compounds on DNA gyrase function, thereby facilitating the creation of novel antimicrobial agents and strategies to address bacterial resistance. Remarkably, metabolites derived from algae, such as those from T. aurea, have demonstrated the ability to inhibit DNA gyrase similarly to synthetic antibiotics. This provides new ways to improve treatment efficacy against resistant bacterial strains and emphasizes the possibility of chemicals derived from algae as natural alternatives to tackle the increasing problem of bacterial resistance.

Materials and methods

Preparation of the Trentepohlia aurea extracts

Trentepohlia aurea (Linnaeus) C. Martius, obtained from Bukit Barisan Grand Forest Park, North Sumatra, Indonesia, was initially cleaned and desiccated. The samples were desiccated in an oven (UN 55 Universal Oven, Memmert, Germany) at 35 °C for 4 - 5 days to eliminate residual moisture. The desiccated algal substance was subsequently pulverized into a fine powder utilizing a blender. Extraction was conducted via the maceration method utilizing 70% methanol for 3 successive cycles, each lasting 24 h, at ambient temperature on a shaker operating at 150 rpm. Following each cycle, the filtrate was extracted from the residue utilizing filter paper. The amalgamated filtrates were concentrated with a rotary evaporator to yield a viscous extract. Using Dimethyl Sulfoxide (DMSO) as the solvent, the concentrated extract was further diluted until it reached a final concentration of 50%. The crude extract yield was 2.78 g, corresponding to 2.78 %(w/w) of the initial dry biomass. No standardization or quantification of total phenolic, flavonoid, or carotenoid content was performed in this study, which is acknowledged as a limitation in interpreting the bioactivity results.

Antibacterial assays of Trentepohlia aurea extracts

Pathogens used for antibacterial activity

In this study, we employed 3 Gram-positive bacterial strains: Staphylococcus aureus ATCC 6538, Propionibacterium acnes ATCC 6919, and Streptococcus mutans ATCC 35668, alongside 3 Gram-negative strains: Salmonella enterica serovar Typhii IPBCC b 11 669, Escherichia coli ATCC 8739, and Pseudomonas aeruginosa ATCC 15442, to evaluate their antimicrobial activity.

Antibacterial activity

The evaluation of antibacterial efficacy was conducted using the disc diffusion method [17-19]. Twenty mL of Mueller-Hinton Agar (MHA) medium was dispensed into sterile Petri dishes and allowed to solidify. A bacterial suspension, adjusted to the turbidity of a 0.5 McFarland standard, was uniformly spread across the agar surface using a sterile cotton swab. Sterile 6 mm discs were impregnated with 100 µL of a 50% methanolic extract of T. aurea and placed onto the inoculated agar. Chloramphenicol served as the positive control and dimethyl sulfoxide (DMSO) as the negative control. The plates were incubated at room temperature for 24 h, and antibacterial activity was determined by measuring the inhibition zone diameters.

GC-MS analysis

A 1 μL volume of the filtered sample, obtained via a membrane filter, was injected into a Shimadzu GCMS-QP2010 Plus for volatile component profiling. Prior to injection, the crude 70% methanol extract obtained by maceration was concentrated and diluted using 2 mL of HPLC-grade methanol (99.5%). No derivatization was performed. The prepared sample was injected using a split ratio of 1:1 through a split-splitless injector maintained at 250 °C, with the mass spectrometer detector temperature set at 280 °C. Separation was achieved on a Restek Rtx®-50 column (Crossbond® 5% phenyl-50% methyl polysiloxane, 30 m×0.25 mm i.d., 0.25 μm film thickness). Helium was used as the carrier gas at 64.1 kPa, with a total flow of 4.9 mL/min, column flow of 0.99 mL/min, linear velocity of 36.6 cm/s, and purge flow of 3.0 mL/min. The oven temperature was programmed from 80 °C (held for 2 min) to 280 °C (held for 8 min). Peak identification was performed using the Wiley9.LIB and cross-validated with the NIST17 library, with a minimum similarity index (SI) threshold of 70 - 80 to confirm compound matches. Compound assignments were based on an internal method following established GC-MS identification criteria. Although the analysis was conducted on a crude methanol extract without preliminary fractionation, this approach was selected to capture the full spectrum of volatile and semi-volatile constituents present in the extract, in line with previous studies reporting reliable bioactive compound detection under similar conditions [18,19].

Protein-ligan preparation

The bioactive compounds from T. aurea used in this study are: Here is a paragraph that includes the compound names with their respective PubChem IDs: Morpholine, 2,6-dimethyl-4-tridecyl- (32518), Carbamic acid, monoammonium salt (517232), Oxiranemethanol (11164), Hexanal (6184), Heptanal (8130), Dianhydroglucitol, tbs 2x, Cyclohexanone, 2,2,6-trimethyl- (17000), 2 octenal (5283324), Cyclopentanone, 2-methyl-3-(1-methylethyl)- (41124), 1-methylcycloheptanol (77376), 1,2,3-propanetriol (753), 2-decenal, (e)- (5283345), 6-methyl-6-nitro-2-heptanone (537587), Isosorbide (12597), (2,2,6,6-tetramethylcyclohexylidene) methanone, 2-Benzofuranmethanol, 2,4,5,6,7,7a-hexahydro-4,4,7a-trimethyl-, cis- (21578471), Phenol, 2,6-dimethoxy- (7041), Trans-. Beta. -ionon-5,6-epoxide, 8-hydroxygeraniol (5363397), 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl- (27209), 1,2,3,4-tetrahydroxybutane (8998), Tetradecanoic acid (11005), Hexadecanoic acid, methyl ester (8181), Aphthosin (15595748), Hexadecanoic acid (985), 10,13-Eicosadienoic acid, methyl ester (5365687). Furthermore, the compound 4-[[8-(methylamino)-2-oxidanylidene-1~{H}-quinolin-3-yl]carbonylamino]benzoic acid9 (Control) (PubChem CID:) was employed as a reference control chemical to evaluate the inhibitory properties of the bioactive compounds obtained from T. aurea. The 2D and 3D structures of the active ingredients found in T. aurea and the control were acquired from the appropriate chemical databases on PubChem. Subsequently, these structures were optimized for energy and transformed into the .pdb file format using Open Babel in PyRx software.

Biological activities prediction using the PASS online

The biological activity prediction of the bioactive compounds from T. aurea was performed using the Prediction of Activity Spectra for Substances (PASS) server on the Way2drug platform (http://way2drug.com/PassOnline/). The SMILES structures of each GC-MS-identified compound were retrieved from the PubChem database (http://pubchem.ncbi.nlm.nih.gov) and submitted individually to the PASS Online server. The prediction results provided probability of activity (Pa) and inactivity (Pi) values for various biological functions. In this study, a Pa value > 0.70 was considered to indicate high potential biological activity, 0.50 ≤ Pa ≤ 0.70 indicated moderate activity, and Pa < 0.50 suggested low activity. Twenty-two compounds with available SMILES data were evaluated, with details presented in Table 2. The combination of high Pa values and low Pi values was used to prioritize compounds for further docking and ADME-toxicity analyses.

Prediction drug-likeness

Lipinski’s rule of 5 was utilized to assess the degree to which the compounds mimicked the properties of drugs. All the compounds were evaluated using SwissADME (http://www.swissadme.ch/), which is a drug-likeness evaluation framework. The number of hydrogen bond acceptors and donors, the molecular weight, and the bioavailability of the molecule are some of the parameters that are included in this resource. It is possible to determine the oral bioavailability of a compound with the help of Lipinski’s rule of 5.

Pharmacokinetics predictions

Pharmacokinetics predictions were evaluated by assessing each compound’s ability to penetrate the blood-brain barrier (BBB) using the pkcSM webserver (http://biosig.lab.uq.edu.au/pkcsm/prediction). Additionally, both BBB permeability and human intestinal absorption (HIA) patterns were analyzed using the BOILED-Egg predictive model.

Molecular docking analysis

Molecular docking was performed to evaluate the binding affinities of the identified compounds toward DNA Gyrase subunit B (PDB ID: 6KZZ). Protein and ligand preparations were conducted using BIOVIA Discovery Studio 2024 for visualization, removal of water molecules and co-crystallized ligands, and the addition of polar hydrogen atoms when necessary. Ligand structures were retrieved from the PubChem database (http://pubchem.ncbi.nlm.nih.gov) in .sdf format, optimized, and converted into .pdbqt format using Open Babel integrated in PyRx v.0.8. DNA Gyrase was selected as it plays a crucial role in bacterial DNA replication and is a well-established target for antibacterial drug development.

Docking simulations were carried out using AutoDock Vina within PyRx 8.0.0, treating the protein as the macromolecule and the bioactive compounds as ligands. The docking grid box was set with center coordinates at (1.3057×1.4901×0.3121) and dimensions of (36.7569×19.5379×18.1727 ų) to encompass the active site. Binding affinity values (kcal/mol) were used to rank ligand–protein interactions, and the interaction profiles were analyzed to identify hydrogen bonds, hydrophobic interactions, and electrostatic contacts. Visualization and identification of key amino acid residues at the binding site were performed using both PyMOL and BIOVIA Discovery Studio 2024.

Results and discussion

T. aurea morphology

T. aurea, a terrestrial filamentous green alga gathered in Bukit Barisan Grand Forest Park, North Sumatra, Indonesia, as illustrated in Figure 1, is a cosmopolitan species with an extensive distribution range. This wide distribution highlights its strong ecological adaptability and ability to occupy diverse ecological niche.

Trentepohlia aurea (L.) C.F.P. Martius, Family: Ulvophyceae. Filamentous form: Fine filaments growing upright in very large numbers, capable of covering extensive surfaces in golden-yellow, yellow-orange, and orange colors. Habitat: Humid, shaded environments, adhering to tree bark, rocks, and moist cement walls. Distribution: Widespread throughout the study area at altitudes ranging from 867 to 978 masl. Characterized by carotenoid pigments that mask green chlorophyll and contribute to its striking yellow-orange coloration. This green alga often symbiotically associates with lichenized fungi, acting as a photobiont in such cases. Identification was based solely on morphological characteristics following relevant taxonomic keys, without voucher specimen deposition or molecular confirmation, which is acknowledged as a limitation given the morphological similarity among members of the order Trentepohliales.

Figure 1 Morphology of T. aurea: (A) Trees covered with massive growth of T. aurea; (B) Population of T. aurea on the tree bark; (C) T. aurea filaments observed under 100× magnification; (D) Carotenoid pigments in T. aurea filaments observed under 400× magnification. (C) and (D) were captured using an Olympus CX43 microscope equipped with a DP75 camera and CellSens Dimensions software.

Antimicrobial activity Trentepohlia aurea

The subsequent table displays the outcomes of antimicrobial activity assays utilizing methanol extracts of T. aurea, assessed against various pathogenic microorganisms. Chloramphenicol (10 µg/disk) was used as a standard antibiotic positive control, and DMSO as a negative control, to enable comparison of the extract’s relative efficacy. Table 1 presents the results of antimicrobial activity testing utilizing methanol extract from T. aurea algae against diverse pathogenic microorganisms. The highest activity is observed against S. aureus, a Gram-positive bacterium, with an inhibition zone 11.3 ± 0.55 mm. Additionally, the methanol extract also exhibits significant antimicrobial activity against S. enterica serovar Typhii 10.9 ± 0.21 mm (Figure 2) and S. mutans 10.8 ± 0.61 mm. However, lower activity is observed against E. coli and P. aeruginosa with inhibition zone 10.0 ± 1.22 mm and 9.8 ± 0.70 mm, respectively. The data suggest that the methanol extract from T. aurea possesses potential as an antimicrobial agent against various bacteria, particularly exhibiting the highest efficacy against Gram-positive bacteria like S. aureus.

Table 1 Antimicrobial efficacy of methanol extract from aerial microalgae T. aurea.

The green alga Trentepohlia umbrina has been previously studied for antimicrobial activity by Simic et al. 20 , whereas studies on the antimicrobial activity of T. aurea are currently being investigated for the first time. Consistent with results from studies on other algae, we observed that the methanol extract of T. aurea exhibited relatively strong antimicrobial activity, more so than Gram-negative bacteria, especially when it comes to Gram-positive bacteria. These differences in antimicrobial activity are attributed to variations in the cell walls of both gram-positive and gram-negative bacteria. Gram-negative bacteria feature 2 lipid membranes with peptidoglycan and lipopolysaccharides (LPS), along with a periplasmic space containing degrading enzymes 21 . The cell walls of Gram-positive bacteria are thick and made of cross-linked peptidoglycan. They also have a single lipid membrane. The structural differences between Gram-positive and Gram-negative bacteria explain why antibacterial agents are more effective against the former 22 .

In addition, carotenoids, including β-carotene, are key compounds found in T. aurea, contributing to its hues ranging from golden-yellow to orange tones [23]. Although research on the antibacterial properties of microalgal β-carotene is limited, recent findings by Jaber and Majeed [24], highlight its potent β-carotene antibacterial activity against various bacteria, particularly Gram-positive strains. These results emphasize β-carotene’s potential as a promising antimicrobial agent.

Figure 2 Inhibition zones of methanol extract of T. aurea against bacteria: (A) Gram-positive bacteria S. aureus (a) - (c). Replicates of methanol extract of T. aurea; (d) Positive control (Chloramphenicol); (e) Negative control (Dimethyl sulfoxide)), and (B) Gram-negative bacteria S. enterica serovar Typhii (a) - (c). Replicates of methanol extract of T. aurea; (d) Positive control (Chloramphenicol); (e) Negative control (Dimethyl sulfoxide).

Gas chromatograpy-mass spectrometry analysis

Raw data from GC-MS and individual chromatograms were processed using Origin software. The GC-MS analysis revealed 26 bioactive compounds in T. aurea. These compounds include Morpholine, 2,6-dimethyl-4-tridecyl-, Carbamic acid, monoammonium salt, Oxiranemethanol, Hexanal, Heptanal, Dianhydroglucitol, tbs 2x, Cyclohexanone, 2,2,6-trimethyl-, 2 octenal, Cyclopentanone, 2-methyl-3-(1-methylethyl)-, 1-methylcycloheptanol, 1,2,3-propanetriol, 2-decenal, (e)-, 6-methyl-6-nitro-2-heptanone, Isosorbide, (2,2,6,6-tetramethylcyclohexylidene) methanone, 2-Benzofuranmethanol, 2,4,5,6,7,7a-hexahydro-4,4,7a-trimethyl-, cis-, Phenol, 2,6-dimethoxy-, Trans-. Beta. -ionon-5,6-epoxide, 8-hydroxygeraniol, 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, 1,2,3,4-tetrahydroxybutane, Tetradecanoic acid, Hexadecanoic acid, methyl ester, Aphthosin, Hexadecanoic acid, 10,13-Eicosadienoic acid, methyl ester. Retention times are presented in Table 2, and the chromatogram is depicted in Figure 3. Based on a screening in PubChem, certain compounds do not possess available 3D structures; therefore, 22 of these compounds catalogued in the database will be employed for docking analysis.

Figure 3 GC-MS Chromatogram of T. Aurea.

Table 2 Compounds of T. aurea (linnaeus) C. martius.

Prediction of compound biological activities

The predicted antimicrobial potential of various compounds from T. aurea, based on their inhibition of key microbial targets, is presented in Table 3. For instance, Morpholine, 2,6-dimethyl-4-tridecyl- shows high activity as a membrane integrity antagonist (Pa = 0.886, Pi = 0.003) and sphinganine kinase inhibitor (Pa = 0.789, Pi = 0.015), both of which can disrupt microbial cell functions. Oxiranemethanol exhibits relatively strong inhibitory potential against glucan endo-1,3-beta-D-glucosidase (Pa = 0.940, Pi = 0.002) and saccharopepsin (Pa = 0.960, Pi = 0.002), which are crucial for microbial cell wall and protein synthesis. Tetradecanoic acid has high inhibitory activity against saccharopepsin (Pa = 0.961, Pi = 0.002) and glucan endo-1,3-beta-D-glucosidase (Pa = 0.945, Pi = 0.002). Similarly, Hexadecanoic acid, methyl ester shows relatively strong potential as a saccharopepsin inhibitor (Pa = 0.962, Pi = 0.002) and chymosin inhibitor (Pa = 0.962, Pi = 0.002). Heptanal is predicted to inhibit exoribonuclease II (Pa = 0.846, Pi = 0.004) and chymosin (Pa = 0.909, Pi = 0.004), while 2-Decenal, (E)- is shown to be an antieczematic agent (Pa = 0.903, Pi = 0.005) and TRPA1 agonist (Pa = 0.705, Pi = 0.002), potentially disrupting microbial integrity. The elevated Pa and diminished Pi values suggest a significant probability of antimicrobial effectiveness, rendering these compounds viable candidates for additional investigation in antimicrobial drug development.

Table 3 Prediction biological activity compounds of T. aurea.

Prediction of drug-likeness

According to Lipinski’s rule of 5, which assesses a compound’s drug-likeness based on molecular weight (MW ≤ 500), lipophilicity (MlogP ≤ 4.15), number of hydrogen bond donors (NHorOH ≤ 5), and acceptors (NorO ≤ 10), Table 4 lists the physicochemical properties of different compounds from T. aurea. Compounds like Carbamic acid, monoammonium salt (MW = 61, MlogP = −6.14, 0 violations), Oxiranemethanol (MW = 74, MlogP = −1.03, 0 violations), Hexanal (MW = 100, MlogP = 1.39, 0 violations), Heptanal (MW = 114, MlogP = 1.74, 0 violations), and 1,2,3-Propanetriol (MW = 92, MlogP = −1.51, 0 violations) show no violations, indicating good drug-like properties and potential oral bioavailability. Others, such as Hexadecanoic acid, methyl ester (MW = 270, MlogP = 4.44, 1 violation) and Hexadecanoic acid (MW = 256, MlogP = 4.19, 1 violation) have slightly higher lipophilicity, leading to one violation, which could affect their absorption or permeability. Aphthosin (MW = 646, MlogP = 2.83, 2 violations) has a high molecular weight and multiple hydrogen bond acceptors, suggesting it may have poor absorption and limited oral bioavailability. Overall, most compounds adhere to Lipinski’s criteria, indicating favorable pharmacokinetic properties, making them promising candidates for further drug development research.

To estimate the likelihood that a chemical molecule with a given pharmacological or biological action will have an oral effect on humans, the Rule of Five (ROF) is used as a general guideline [25]. The ROF rating for an orally active medicine ranges from “0” to “4”, indicating no more than one violation of the exposed criterion. Lipinski cautions against dismissing these molecules entirely, as many medicines do not undergo ROF [26]. Although the rule of 5 has a broad application, there are certain flaws. The 2 key drawbacks are the equal weight given to each rule and the sharp boundary that signals a breach of a specific rule. Another problem of this approach is that it does not consider natural and biological compounds. ROF excludes metabolic-related criteria.

Table 4 Physicochemical properties of compounds from T. aurea.

Pharmacokinetics prediction

The pharmacokinetic evaluation of T. aurea compounds, shown in Table 5, reveals diverse absorption, distribution, and metabolic characteristics. HIA rates range from 51.7% to 97.5%, with most compounds exceeding 90%, indicating efficient gastrointestinal absorption. Caco-2 permeability values for all compounds are greater than 1, suggesting effective traversal of the intestinal epithelial barrier, a critical factor for oral bioavailability. Among the compounds, Morpholine, 2,6-dimethyl-4-tridecyl-, stands out as both a substrate and inhibitor of the CYP2D6 enzyme and interacts with the OCT2 transporter, hinting at potential metabolic and renal transport complexities. In contrast, most compounds, including Hexanal, Heptanal, and Cyclopentanone derivatives, do not exhibit CYP2D6 or OCT2 interactions, suggesting stable metabolic and renal profiles. Water solubility varies significantly, with compounds like Oxiranemethanol and 1,2,3-propanetriol demonstrating high solubility, supporting their absorption. Conversely, lipophilic compounds such as Hexadecanoic acid and its methyl ester exhibit poor solubility (log mol/L < −6), which may influence their bioavailability despite favorable absorption rates. BBB permeability analysis reveals that most compounds, such as Hexadecanoic acid and its methyl ester, possess moderate to high permeability (log BB values between 0.5 and 0.7), indicating their potential to reach the central nervous system (CNS). Compounds like Carbamic acid, monoammonium salt, show limited BBB penetration (log BB < 0), restricting their CNS access. These findings highlight the varied pharmacokinetic potential of T. aurea compounds, with most demonstrating effective gastrointestinal absorption, some capable of CNS permeation, and others maintaining metabolic stability. This diversity suggests promising applications for these compounds in pharmacological development.

Table 5 Pharmacokinetic characteristics of compounds from T. Aurea.