Structure-Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors.

Approved and potent reported dipeptidyl peptidase-4 (DPP-4) inhibitors with gliptin-like structures are classified here according to their structures and mechanisms of the inhibition in three groups: (i) those with pyrrolidine or analogs as P1 fragment with α-aminoacyl linker, (ii) structures with trifluorophenyl moiety or analogs as P1 fragment with ß-aminobutanoyl linker, and (iii) DPP-4 inhibitors with pyrimidine-2,4-dione or analogs as P1' fragment. The structure-activity relationship analysis was performed for those whose cocrystallized structures with the enzyme were published. While inhibitors with pyrrolidine and trifluorophenyl moiety or analogs as P1 fragment bind in a similar way in S1, S2 and S2 extensive domains of the enzyme, the binding mode of pyrimidine-2,4-dione derivatives/analogs differs with additional interactions in S1' and S2' pockets. Three general schemes of fragmented gliptins and gliptin-like structures with the enzyme and protein-ligand interaction fingerprints were made, which might be useful in the creation of DPP-4 inhibitor's design strategies.

1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors.

Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 µM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50 =134.35±11.38 µM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50 =147.51±14.87 µM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50 =149.07±2.98 µM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50 =148.31±2.96 µM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.

Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase.

In this study, seven new 4-oxothiazolidine derivatives were synthesized and assayed, along 7 known derivatives, for inhibitory properties against deoxyribonuclease I (DNase I) and xanthine oxidase (XO) in vitro. Among tested compounds, (5Z)-Ethyl-2-(2-(cyanomethylene)-4-oxothiazolidin-5-yliden)acetate (6) exhibited inhibitory activity against both enzymes (DNase I IC50 = 67.94 ± 5.99 µM; XO IC50 = 98.98 ± 13.47 µM), therefore being the first reported dual inhibitor of DNase I and XO. Observed DNase I inhibition qualifies compound 6 as the most potent small organic DNase I inhibitor reported so far. Derivatives of 2-alkyliden-4-oxothiazolidinone (1) inhibited DNase I below 200 µM, while the other tested 4-oxothiazolidine derivatives remained inactive against both enzymes. The molecular docking and molecular dynamics simulations into the binding sites of DNase I and XO enzyme allowed us to clarify the binding modes of this 4-oxothiazolidine derivative, which might aid future development of dual DNase I and XO.

Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives.

Deoxyribonuclease I (DNase I) inhibitory properties of two 1-(pyrrolidin-2-yl)propan-2-one derivatives were examined in vitro. Determined IC50 values of 1-[1-(4-methoxyphenyl)pyrrolidin-2-yl]propan-2-one (1) (192.13±16.95 µM) and 1-[1-(3,4,5-trimethoxyphenyl)pyrrolidin-2-yl]propan-2-one (2) (132.62±9.92 µM) exceed IC50 value of crystal violet, used as a positive control, 1.89- and 2.73-times, respectively. Compounds are predicted to be nontoxic and to have favorable pharmacokinetic profiles, with high gastrointestinal absorption and blood-brain barrier permeability. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, Glu 78, Arg 111, Pro 137, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Determined inhibitory properties along with predicted ADMET profiles and observed interactions would be beneficial for the discovery of new active 1-(pyrrolidin-2-yl)propan-2-one-based inhibitors of DNase I.

4-(4-Chlorophenyl)thiazol-2-amines as pioneers of potential neurodegenerative therapeutics with anti-inflammatory properties based on dual DNase I and 5-LO inhibition.

Eleven new 4-(4-chlorophenyl)thiazol-2-amines were synthesized and, together with nine known derivatives, evaluated in vitro for inhibitory properties towards bovine pancreatic DNase I. Three compounds (18-20) inhibited DNase I with IC50 values below 100 µM, with compound 19 being the most potent (IC50 = 79.79 µM). Crystal violet, used as a positive control in the absence of a "golden standard", exhibited almost 5-fold weaker DNase I inhibition. Pharma/E-State RQSAR models clarified critical structural fragments relevant for DNase I inhibition. Molecular docking and molecular dynamics simulation defined the 4-(4-chlorophenyl)thiazol-2-amines interactions with the most important catalytic residues of DNase I. Ligand-based pharmacophore modeling and virtual screening confirmed the chemical features of 4-(4-chlorophenyl)thiazol-2-amines required for DNase I inhibition and proved the absence of structurally similar molecules in available databases. Compounds 18-20 have been shown as very potent 5-LO inhibitors with nanomolar IC50 values obtained in cell-free assay, with compound 20 being the most potent (IC50 = 50 nM). Molecular docking and molecular dynamics simulations into the binding site of 5-LO enzyme allowed us to clarify the binding mode of these dual DNase I/5-LO inhibitors. It was shown that compounds 18-20 uniquely show interactions with histidine residues in the catalytic site of DNase I and 5-LO enzyme. In the absence of potent organic DNase I inhibitors, compounds 18-20 represent a good starting point for the development of novel Alzheimer's therapeutics based on dual 5-LO and DNase I inhibition, which also have anti-inflammatory properties.

Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors.

Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo[3,2-a]benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 µM, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 µM. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.

Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4.

A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14) as the most effective inhibitor (IC50 = 34.17 ± 5.11 µM). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 µM. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme-inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.

Synthesis and DNase I inhibitory properties of some 4-thiazolidinone derivatives.

Twelve new thiazolidinones were synthesized and, together with 41 previously synthesized thiazolidinones, evaluated for inhibitory activity against deoxyribonuclease I (DNase I) in vitro. Ten compounds inhibited commercial bovine pancreatic DNase I with an IC50 below 200 µM and showed to be more potent DNase I inhibitors than crystal violet (IC50 = 365.90 ± 47.33 µM), used as a positive control. Moreover, three compounds were active against DNase I in rat liver homogenate, having an IC50 below 200 µM. (3-Methyl-1,4-dioxothiazolidin-2-ylidene)-N-(2-phenylethyl)ethanamide (41) exhibited the most potent DNase I inhibition against both commercial and rat liver DNase I with IC50 values of 115.96 ± 11.70 and 151.36 ± 15.85 µM, respectively. Site Finder and molecular docking defined the thiazolidinones interactions with the most important catalytic residues of DNase I, including the H-acceptor interaction with residues His 134 and His 252 and/or H-donor interaction with residues Glu 39 and Asp 168. The three most active compounds against both commercial and rat liver DNase I (31, 38, and 41) exhibited favorable physico-chemical, pharmacokinetic, and toxicological properties. These observations could be utilized to guide the rational design and optimization of novel thiazolidinone inhibitors. Thiazolidinones as novel DNase I inhibitors could have potential therapeutic applications due to the significant involvement of DNase I in the pathophysiology of many disease conditions.

Synthesis and DNase I inhibitory properties of some 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines.

A series of six novel and six known thieno[2,3-d]pyrimidin-4-amines 2-13 were synthesized, and further were used as a starting material for preparation of a small series of eight novel thieno[2,3-d]pyrimidin-4-phthalimides 14-21. Eight compounds, five amine and three phthalimide derivatives, inhibited bovine pancreatic DNase I with an IC50 below 200 µM, being more effective than referent inhibitor crystal violet. Phthalimide derivatives 16, 18 and 19 exhibited higher DNase I inhibitory activity compared to their amine precursors 7, 10 and 11. Compound 19, as the most potent (IC50 = 106 ±â€¯16 µM), offers a good starting point for a design of new DNase I inhibitors. The Pharma RQSAR model showed a significant enhancement of thieno[2,3-d]pyrimidines activity using aryl substituents at R1 position. The E-State RQSAR model clarified the most important structural fragments relevant for DNase I inhibition. Molecular docking and Site Finder module defined the thieno[2,3-d]pyrimidines interactions with the most important catalytic residues of DNase I, including Glu 39, His 134, Asp 168 and His 252. We also found that steric effects and increase of molecular volume play a vital role in DNase I inhibition.

Benzimidazoles as novel deoxyribonuclease I inhibitors.

Inhibitory potential of 19 benzimidazoles against bovine pancreatic deoxyribonuclease I (DNase I) was investigated in vitro. Three compounds inhibited DNase I with IC50 below 100 µM and proved to be more potent DNase I inhibitors than crystal violet (IC50 = 351.82 ± 29.41 µM), used as a positive control. Compound 9 showed the most potent DNase I inhibition with an IC 50 value of 79.46 ± 11.75 µM. To further explore the relationship between inhibitory activity and 2D pharmacophore features, Pharma/E-State R-group quantitative structure-activity relationship (RQSAR) models were generated and validated using Schrödinger Suite. RQSAR models showed a significant enhancement of benzimidazoles activity using hydrogen-bond acceptor substituents at the R2, R3, and R4 positions, or aryl substituents at the R4 position. The Site Finder module and molecular docking defined the benzimidazoles interactions with the most important catalytic residues of DNase I, including H-acceptor interaction with residue His 134 and His 252 and/or H-donor interaction with residue Glu 39. We also found a positive correlation between IC50 inhibition values and relative binding free energies of the most active benzimidazoles. In addition, a molecular dynamics simulation was performed for DNase I-compound 9 docking complex in Desmond. Trajectory analysis showed that docking complex and intermolecular interactions were stable throughout the entire production part of simulations. Furthermore, the results of protein structure alignment module suggested the potential translational impact of benzimidazoles against human DNase I. Due to the significant involvement of DNase I in the pathophysiology of many disease conditions, benzimidazoles as DNase I inhibitors could have potential therapeutic applications.

Ascorbic acid as DNase I inhibitor in prevention of male infertility.

Apoptotic and/or ROS-induced DNA fragmentation in sperm cells may contribute to the development of male infertility. As the known dietary antioxidant, ascorbic acid prevents ROS production and protects sperm cells from DNA damage. Here, we found that ascorbic acid has the ability to inhibit DNase I, one of the main endonucleases involved in DNA fragmentation during apoptosis. Site Finder and Molecular docking defined the ascorbic acid interactions with the most important residues of DNase I, including H-donor interactions with Asp 168 and Asn 170, and H-acceptor interaction with Asn 170. As a furan derivative, ascorbic acid could be considered a pioneer of substrate-based DNase I inhibitors. The results indicate to another possible mechanism for prevention of male infertility by ascorbic acid.

In Vitro Trials of Dittrichia graveolens Essential Oil Combined with Antibiotics.

The chemical composition and antibacterial activity of Dittrichia graveolens (L.) Greuter essential oil were examined. Gas chromatography and gas chromatography/mass spectrometry were used to analyze the chemical composition of the essential oil. The antibacterial activity was investigated by the broth microdilution method against thirteen bacterial strains. The interactions of the essential oil and three standard antibiotics: chloramphenicol, tetracycline and streptomycin toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods: principal components analysis and hierarchical cluster analysis. Oxygenated monoterpenes were the most abundant compound class in the essential oil (40.6%), with bomyl acetate (21.7%) as the major compound. The essential oil exhibited slight antibacterial activity against the tested bacterial strains in vitro, but the combinations D. graveolens essential oil-chloramphenicol and D. graveolens-tetracycline exhibited mostly synergistic or additive interactions. These combinations reduced the minimum effective dose of the antibiotics and, consequently, minimized their adverse side effects. In contrast, the association of D. graveolens essential oil and streptomycin was characterized by strong antagonistic interactions against E. coli ATCC 25922, S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. In the principal components analysis (PCA) and hierarchical cluster analysis (HCA), streptomycin against these bacterial strains stood out and formed a separate group.

Chemoinformatics Approach to Antibacterial Studies of Essential Oils.

The chemical composition and antibacterial activity of Nepeta nuda (Lamiaceae) essential oil were examined, as well as the association between it and standard antibiotics: tetracycline and streptomycin. The antibacterial activities of 1,8-cineole, the main constituent of N. nuda oil, individually and in combination with standard antibiotics were also determined. The interactions of the essential oil and 1,8-cineole with antibiotics toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemoinformatics methods. Oxygenated monoterpenes were the most abundant compound class in the oil (57.8%), with 1,8-cineole (46.0%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antibiotics. The combinations N. nuda oil-antibiotic and 1,8-cineole-antibiotic produced a predominantly antagonistic interactions. Chemoinformatics survey confirms the antagonistic interactions as a consequence of membrane potential/proton motive force dissipation. These data indicate cytochrome c oxidase as a target for 1.8-cineole toxicity action mechanisms.

Antibacterial Investigation of Thyme Essential Oil and Its Main Constituents in Combination with Tetracycline.

The chemical composition and antibacterial activity of Thymus glabrescens Willd. (thyme) essential oil were examined, as well as its association with tetracycline. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, were also determined. Gas chromatography and gas chromatography/mass spectrometry were used to analyze the chemical composition of the oil. The antibacterial activities of the oil, geraniol, and thymol were investigated by the broth microdilution method. The interactions of the essential oil, geraniol, and thymol with tetracycline, toward five selected strains, were evaluated using the microdilution checkerboard assay. Oxygenated monoterpenes were the most abundant compound class in the oil (57.14%), with geraniol (22.33%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains. The combinations, essential oil-tetracycline and thymol-tetracycline, produced synergistic interaction to a greater extent compared with geraniol-tetracycline association. All synergistic combinations reduced the minimum effective dose of the antibiotic and, consequently, minimized its adverse side effects.

In vitro interactions of Peucedanum officinale essential oil with antibiotics.

The chemical composition and antibacterial activity of Peucedanum officinale L. (Apiaceae) essential oil were examined, as well as the association between it and antibiotics: tetracycline, streptomycin and chloramphenicol. The interactions of the essential oil with antibiotics were evaluated using the microdilution checkerboard assay. Monoterpene hydrocarbons, with α-phellandrene as the dominant constituent, were the most abundant compound class of the essential oil of P. officinale. The researched essential oil exhibited slight antibacterial activity against the tested bacterial strains in vitro. On the contrary, essential oil of P. officinale possesses a great synergistic potential with chloramphenicol and tetracycline. Their combinations reduced the minimum effective dose of the antibiotic and, consequently, minimised its adverse side effects. In addition, investigated interactions are especially successful against Gram-negative bacteria, the pharmacological treatment of which is very difficult nowadays.

An in vitro antibacterial study of savory essential oil and geraniol in combination with standard antimicrobials.

The chemical composition and antibacterial activity of Satureja kitaibelii Wierzb. ex Heuff. (savory) essential oil were examined, as well as the association between it and standard antimicrobials: tetracycline and chloramphenicol. The antibacterial activities of geraniol, the main constituent of S. kitaibelii oil, individually and in combination with standard antimicrobials were also determined. The interactions of the essential oil and geraniol with antimicrobials toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil (59.7%), with geraniol (50.4%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antimicrobials. The combinations savory oil-chloramphenicol, savory oil-tetracycline and geraniol-chloramphenicol produced predominantly synergistic interactions (FIC indices in the range 0.21-0.87) and substantial reductions in the MIC values of antimicrobials against Gram-negative bacteria, the pharmacological treatment of which is very difficult nowadays. In the PCA and HCA analyses these combinations form a separate group.

In vitro antibacterial activity of Libanotis montana essential oil in combination with conventional antibiotics.

The chemical composition and antibacterial activity were examined of Libanotis montana Crantz subsp. leiocarpa (Heuff.) Soó. (Apiaceae) essential oil. Gas chromatography and gas chromatography/mass spectrometry were used to analyze the chemical composition of the oil. The antibacterial activity was investigated by the broth microdilution method against thirteen bacterial strains. The interactions of the essential oil and three standard antibiotics: tetracycline, streptomycin and chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods: principal components analysis and hierarchical cluster analysis. Sesquiterpene hydrocarbons were the most abundant compound class in the oil (67.2%), with beta-elemene (40.4%) as the major compound. The essential oil exhibited slight antibacterial activity against the tested bacterial strains in vitro, but the combinations L. montana oil-chloramphenicol and L. montana oil-tetracycline exhibited mostly either synergistic or additive interactions. These combinations reduced the minimum effective dose of the antibiotics and, consequently, minimized their adverse side effects. In contrast, the association of L. montana essential oil and streptomycin was characterized by strong antagonistic interactions against Escherichia coli ATCC 25922. In the PCA and HCA analyses, streptomycin stood out and formed a separate group.

An in vitro synergistic interaction of combinations of Thymus glabrescens essential oil and its main constituents with chloramphenicol.

The chemical composition and antibacterial activity of Thymus glabrescens Willd. (Lamiaceae) essential oil were examined, as well as the association between it and chloramphenicol. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, individually and in combination with chloramphenicol, were also determined. The interactions of the essential oil, geraniol, and thymol with chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil, with geraniol (22.33%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antibiotic and thymol. A combination of T. glabrescens oil and chloramphenicol produced a strong synergistic interaction (FIC indices in the range 0.21-0.87) and a substantial reduction of the MIC value of chloramphenicol, thus minimizing its adverse side effects. The combinations geraniol-chloramphenicol and thymol-chloramphenicol produced synergistic interaction to a greater extent, compared with essential oil-chloramphenicol association, which may indicate that the activity of the thyme oil could be attributed to the presence of significant concentrations of geraniol and thymol.

Antibacterial activity of the essential oil of Heracleum sibiricum.

The composition and antimicrobial activity of the essential oil of Heracleum sibiricum L. (Apiaceae) was studied. The aerial part of plant was hydro-distilled and chemical composition of the essential oil was analyzed by GC and GC-MS. Forty-six compounds, corresponding to 95.12% of the total oil, were identified. Esters represented the major chemical class (69.55%) while the main constituents were octyl butanoate (36.82%), hexyl butanoate (16.08%), 1-octanol (13.62%) and octyl hexanoate (8.10%). Antibacterial activity of the essential oil and reference antibiotics against nine bacterial strains was tested by the broth microdilution method. The results of the bioassays showed that essential oil had slight antimicrobial activities against all tested microorganisms (MIC and MBC values were in the range of 2431.2 to 9724.8 microg/mL). Reference antibiotics were active in concentrations between 0.5 and 16.0 microg/mL. The results confirm that Gram-positive bacteria were more susceptible to the essential oil of H. sibiricum, in comparison with Gram-negative bacteria.

Investigation of the chemical composition-antibacterial activity relationship of essential oils by chemometric methods.

The antibacterial effects of Thymus vulgaris (Lamiaceae), Lavandula angustifolia (Lamiaceae), and Calamintha nepeta (Lamiaceae) Savi subsp. nepeta var. subisodonda (Borb.) Hayek essential oils on five different bacteria were estimated. Laboratory control strain and clinical isolates from different pathogenic media were researched by broth microdilution method, with an emphasis on a chemical composition-antibacterial activity relationship. The main constituents of thyme oil were thymol (59.95%) and p-cymene (18.34%). Linalool acetate (38.23%) and ß-linalool (35.01%) were main compounds in lavender oil. C. nepeta essential oil was characterized by a high percentage of piperitone oxide (59.07%) and limonene (9.05%). Essential oils have been found to have antimicrobial activity against all tested microorganisms. Classification and comparison of essential oils on the basis of their chemical composition and antibacterial activity were made by utilization of appropriate chemometric methods. The chemical principal component analysis (PCA) and hierachical cluster analysis (HCA) separated essential oils into two groups and two sub-groups. Thyme essential oil forms separate chemical HCA group and exhibits highest antibacterial activity, similar to tetracycline. Essential oils of lavender and C. nepeta in the same chemical HCA group were classified in different groups, within antibacterial PCA and HCA analyses. Lavender oil exhibits higher antibacterial ability in comparison with C. nepeta essential oil, probably based on the concept of synergistic activity of essential oil components.