Antimicrobial Action Mechanisms of Natural Compounds Isolated from Endophytic Microorganisms.

Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites.

Evaluation of the Local Anesthetic Activity, Acute Toxicity, and Structure-Toxicity Relationship in Series of Synthesized 1-Aryltetrahydroisoquinoline Alkaloid Derivatives In Vivo and In Silico.

Isoquinoline alkaloids constitute one of the most common classes of alkaloids that have shown a pronounced role in curing various diseases. Finding ways to reduce the toxicity of these molecules and to increase their therapeutic margin is an urgent matter. Here, a one-step method for the synthesis of a series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines was performed in 85-98% yield by the Pictet-Spengler reaction. This was accomplished using the reaction between 3,4-dimethoxyphenylethylamine and substituted benzaldehydes boiling in trifluoroacetic acid. Furthermore, 1-(3'-amino-, 4'-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were obtained in 94% and 97% yield by reduction in 1-(3'-nitro-, 4'-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl2 × 2H2O. The structures of the substances obtained were confirmed by infrared (IR) and nuclear magnetic resonance (1H and 13C NMR) spectra. ADMET/TOPKAT in silico study concluded that the synthesized compounds exhibited acceptable pharmacodynamic and pharmacokinetic properties without carcinogenic or mutagenic potential but with variable hepatotoxicity. The acute toxicity and structure-toxicity relationship (STR) in the series of 20 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (3a-r, 4a, b) was studied via determination of acute toxicity and resorptive action in white mice employing intragastric step-by-step administration. The first compound, 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3a), showed the highest toxicity with LD50 of 280 mg/kg in contrast to 1-(3'-bromo -4'-hydroxyphenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3e) which proved to be the safest of the compounds studied. Its toxicity was 13.75 times lower than that of the parent compound 3a. All compounds investigated showed high local anesthetic activity on rabbit eyes in the concentrations studied. Only 3r, 3n, and 4a caused eye irritation and redness. All investigated derivatives (except 4b) in 1% concentration were more active than lidocaine, providing longer duration of complete anesthesia. Therefore, based on the obtained results of in silico tests, local anesthesia, and acute toxicity, a conclusion can be drawn that the experimental compounds need further extensive future investigations and possible modifications so that they can act as promising drug candidates.

Lehmanniaside, a new cycloartane triterpene glycoside from Astragalus lehmannianus.

Chemical investigation of the aerial parts of Astragalus lehmannianus Bunge (Leguminosae) led to the isolation and identification of a new cycloartane triterpene glycoside - lehmanniaside (2'-O-acetyl-3-ß-O-D-xylopyranosyl-3ß,6α,16ß,24α-tetrahydroxy-20,25-epoxycycloartane). Its structure was elucidated by means of spectroscopic analysis (HR-MS, 1D and 2D NMR). Bioassays showed that lehmanniaside exhibits weak anthelmintic, antifungal, and cytotoxic activities.

Silviridoside: A New Triterpene Glycoside from Silene viridiflora with Promising Antioxidant and Enzyme Inhibitory Potential.

A new triterpene glycoside, silviridoside, was isolated from the aerial parts of Silene viridiflora (Caryophyllaceae) using different chromatographic techniques. The structure of silviridoside was comprehensively elucidated as 3-O-ß-D-galacturonopyranosyl-quillaic acid 28-O-ß-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-fucopyranosyl ester by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Silviridoside showed promising antioxidant activity in different antioxidant assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) (2.32 mg TE/g), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (1.24 mg TE/g), cupric-reducing antioxidant capacity (CUPRAC) (9.59 mg TE/g), ferric-reducing antioxidant power (FRAP) (5.13 mg TE/g), phosphomolybdenum (PHD) (0.28 mmol TE/g), and metal-chelating (MCA) (6.62 mg EDTA/g) assays. It exhibited a good inhibitory potential on acetylcholinesterase (AChE) (2.52 mg GALAE/g), butyrylcholinesterase (BChE) (7.16 mg GALAE/g), α-amylase (0.19 mmol ACAE/g), α-glucosidase (1.21 mmol ACAE/g), and tyrosinase (38.83 mg KAE/g). An in silico evaluation of the pharmacodynamic, pharmacokinetic, and toxicity properties of silviridoside showed that the new compound exhibited reasonable pharmacodynamic and pharmacokinetic properties without any mutagenic effect, but slight toxicity. Thus, it could be concluded that silviridoside could act as a promising lead drug for pharmaceutical and nutraceutical developments to combat oxidative stress and various disorders, but a future optimization is necessary.

GC-MS Chemical Profiling, Biological Investigation of Three Salvia Species Growing in Uzbekistan.

Salvia is a potentially valuable aromatic herb that has been used since ancient times. The present work studied the chemical profile of three Salvia species essential oils (EO): S. officinalis, S. virgata and S. sclarea, as well as assessing their antioxidant and enzyme inhibitory activities. A total of 144 compounds were detected by GC-MS analysis, representing 91.1, 84.7 and 78.1% in S. officinalis, S. virgata and S. sclarea EOs, respectively. The major constituents were cis-thujone, 2,4-hexadienal and 9-octadecenoic acid, respectively. The principal component analysis (PCA) score plot revealed significant discrimination between the three species. The antioxidant activity of the EOs was evaluated using in vitro assays. Only S. virgata EO showed antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay (26.6 ± 1.60 mg Trolox equivalent (TE)/g oil). Moreover, this oil exhibited the highest antioxidant activity in 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing power (FRAP) assays in comparison with the other two EOs (190.1 ± 2.04 vs. 275.2 ± 8.50 and 155.9 ± 1.33 mg TE/g oil, respectively). However, S. virgata oil did not show any effect in the chelating ability assay, while in the PBD assay, S. officinalis had the best antioxidant activity (26.4 ± 0.16 mmol TE/g oil). Enzyme inhibitory effect of the EOs was assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, α-glucosidase and α-amylase. AChE enzyme was more sensitive to S. officinalis EO (4.2 ± 0.01 mg galantamine equivalent (GALAE)/g oil), rather than S. virgata EO, which was ineffective. However, S. virgata had the highest BChE effect (12.1 ± 0.16 mg GALAE/g oil). All studied oils showed good tyrosinase inhibitory activity, ranging between 66.1 ± 0.61 and 128.4 ± 4.35 mg kojic acid equivalent (KAE)/g oil). Moreover, the EOs did not exhibit any glucosidase inhibition and were weak or inefficient on amylase enzyme. Partial least squares regression (PLS-R) models showed that there is an excellent correlation between the antioxidant activity and the volatile profile when being compared to that of enzyme inhibitory activity. Thus, the studied Salvia essential oils are interesting candidates that could be used in drug discovery for the management of Alzheimer's and hyperpigmentation conditions.

Ecdysteroids as Potent Enzyme Inhibitors and Verification of Their Activity Using In Vitro and In Silico Docking Studies.

Ecdysteroids represent arthropods' steroidal hormones, and they exist in about 5-6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri-O-acetate (4) showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E (7) with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide (18) (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E (7) showed the best ranking score with a docking score of -5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential.

Fruit Peels: Food Waste as a Valuable Source of Bioactive Natural Products for Drug Discovery.

Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications.

Chemometric Analysis Based on GC-MS Chemical Profiles of Three Stachys Species from Uzbekistan and Their Biological Activity.

The chemical composition of the essential oils (EOs) of Stachys byzantina, S. hissarica and S. betoniciflora growing in Uzbekistan were determined, and their antioxidant and enzyme inhibitory activity were assessed. A gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of 143 metabolites accounting for 70.34, 76.78 and 88.63% of the total identified components of S. byzantina, S. hissarica and S. betoniciflora, respectively. Octadecanal (9.37%) was the most predominant in S. betoniciflora. However, n-butyl octadecenoate (4.92%) was the major volatile in S. byzantina. Benzaldehyde (5.01%) was present at a higher percentage in S. hissarica. A chemometric analysis revealed the ability of volatile profiling to discriminate between the studied Stachys species. The principal component analysis plot displayed a clear diversity of Stachys species where the octadecanal and benzaldehyde were the main discriminating markers. The antioxidant activity was evaluated in vitro using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP), chelating and phosphomolybdenum (PBD). Moreover, the ability of the essential oils to inhibit both acetyl/butyrylcholinesterases (AChE and BChE), α-amylase, α-glucosidase and tyrosinase was assessed. The volatiles from S. hissarica exhibited the highest activity in both the ABTS (226.48 ± 1.75 mg Trolox equivalent (TE)/g oil) and FRAP (109.55 ± 3.24 mg TE/g oil) assays. However, S. betoniciflora displayed the strongest activity in the other assays (174.94 ± 0.20 mg TE/g oil for CUPRAC, 60.11 ± 0.36 mg EDTA equivalent (EDTAE)/g oil for chelating and 28.24 ± 1.00 (mmol TE/g oil) for PBD. Regarding the enzyme inhibitory activity, S. byzantina demonstrated the strongest AChE (5.64 ± 0.04 mg galantamine equivalent (GALAE)/g oil) and tyrosinase inhibitory (101.07 ± 0.60 mg kojic acid equivalent (KAE)/g) activity. The highest activity for BChE (11.18 ± 0.19 mg GALAE/g oil), amylase inhibition (0.76 ± 0.02 mmol acarbose equivalent (ACAE)/g oil) and glucosidase inhibition (24.11 ± 0.06 mmol ACAE/g oil) was observed in S. betoniciflora. These results showed that EOs of Stachys species could be used as antioxidant, hypoglycemic and skincare agents.

Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies, and the Evaluation of Their ADMET Properties.

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes' potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 2',3',4',7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (-7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.

Discrimination of the Essential Oils Obtained from Four Apiaceae Species Using Multivariate Analysis Based on the Chemical Compositions and Their Biological Activity.

The chemical composition of the essential oils obtained from the aerial parts of four Apiaceae species, namely Elaeosticta allioides (EA), E. polycarpa (EP), Ferula clematidifolia (FC), and Hyalolaena intermedia (HI), were determined using gas chromatography. Altogether, 100 volatile metabolites representing 78.97, 81.03, 85.78, and 84.49% of the total components present in EA, EP, FC, and HI oils, respectively, were reported. allo-Ocimene (14.55%) was the major component in FC, followed by D-limonene (9.42%). However, in EA, germacrene D (16.09%) was present in a high amount, while heptanal (36.89%) was the predominant compound in HI. The gas chromatographic data were subjected to principal component analysis (PCA) to explore the correlations between these species. Fortunately, the PCA score plot could differentiate between the species and correlate Ferula to Elaeosticta species. Additionally, the antioxidant activity was evaluated in vitro using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and the ferric reducing power (FRAP) assays. In addition, the antimicrobial activity using the agar diffusion method was assessed, and the minimum inhibitory concentrations (MICs) were determined. Furthermore, the cell viability MTT assay was performed to evaluate the cytotoxicity of the essential oils against hepatic (HepG-2) and cervical (HeLa) cancer cell lines. In the DPPH assay, FC exhibited the maximum activity against all the antioxidant assays with IC50 values of 19.8 and 23.0 µg/mL for the DPPH and ABTS assays, respectively. Ferula showed superior antimicrobial and cytotoxic activities as well. Finally, a partial least square regression model was constructed to predict the antioxidant capacity by utilizing the metabolite profiling data. The model showed excellent predictive ability by applying the ABTS assay.

Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology.

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

Sugar Containing Compounds and Biological Activities of Lagochilus setulosus.

Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-ß-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-ß-glucoside (2), stigmasterol-3-O-ß-glucoside (3), pinitol (4), 6ß-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.

GC-MS Based Identification of the Volatile Components of Six Astragalus Species from Uzbekistan and Their Biological Activity.

The compositions of volatile components in the aerial parts of six Astragalus species, namely A. campylotrichus (Aca), A. chiwensis (Ach), A. lehmannianus (Ale), A. macronyx (Ama), A. mucidus (Amu) and A. sieversianus (Asi), were investigated using gas chromatograph-mass spectrometry (GC-MS) analysis. Ninety-seven metabolites were identified, accounting for 73.28, 87.03, 74.38, 87.93, 85.83, and 91.39% of Aca, Ach, Ale, Ama, Amu and Asi whole oils, respectively. Sylvestrene was the most predominant component in Asi, Amu and Ama, with highest concentration in Asi (64.64%). In addition, (E)-2-hexenal was present in a high percentage in both Ale and Ach (9.97 and 10.1%, respectively). GC-MS based metabolites were subjected to principal component analysis (PCA) and hierarchal cluster analysis (HCA) to explore the correlations between the six species. The PCA score plot displayed clear differentiation of all Astragalus species and a high correlation between the Amu and Ama species. The antioxidant activity was evaluated in vitro using various assays, phosphomolybdenum (PM), 2,2 diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP) and ferrous ion chelation (FIC) assays. In addition, the potential for the volatile samples to inhibit both acetyl/butyrylcholinesterases (AChE, BChE), α- amylase, α-glucosidase and tyrosinase was assessed. Most of the species showed considerable antioxidant potential in the performed assays. In the DPPH assay, Ama exhibited the maximum activity (24.12 ± 2.24 mg TE/g sample), and the volatiles from Amu exhibited the highest activity (91.54 mgTE/g oil) in the ABTS radical scavenging assay. The effect was more evident in both CUPRAC and FRAP assays, where both Ale and Ama showed the strongest activity in comparison with the other tested species (84.06, 80.28 mgTE/g oil for CUPRAC and 49.47, 49.02 mgTE/g oil for FRAP, respectively). Asi demonstrated the strongest AChE (4.55 mg GALAE/g oil) and BChE (3.61 mg GALAE/g oil) inhibitory effect. Furthermore, the best tyrosinase inhibitory potential was observed for Ale (138.42 mg KAE/g). Accordingly, Astragalus species can be utilized as promising natural sources for many medicinally important components that could be tested as drug candidates for treating illnesses such as Alzheimer's disease, diabetes mellitus and oxidative stress-related diseases.

The Genus Lagochilus (Lamiaceae): A Review of Its Diversity, Ethnobotany, Phytochemistry, and Pharmacology.

The genus Lagochilus (Lamiaceae) is native to Central, South-Central, and Eastern Asia. It comprises 44 species, which have been commonly used as herbal medicines for the treatments of various ailments for thousands of years, especially in Asian countries. This review aims to summarize the chemical constituents and pharmacological activities of species from the genus Lagochilus to unveil opportunities for future research. In addition, we provide some information about their traditional uses, botany, and diversity. More than 150 secondary metabolites have been reported from Lagochilus, including diterpenes, flavonoids, phenolic compounds, triterpenoids, iridoid glycosides, lignans, steroids, alkaloids, polysaccharides, volatile, non-volatile and aromatic compounds, lipids, carbohydrates, minerals, vitamins, and other secondary metabolites. In vitro and in vivo pharmacological studies on the crude extracts, fractions, and isolated compounds from Lagochilus species showed hemostatic, antibacterial, anti-inflammatory, anti-allergic, cytotoxic, enzyme inhibitory, antispasmodic, hypotensive, sedative, psychoactive, and other activities.

Diterpenes from an Uzbek medicinal plant Perovskia scrophulariifolia: Their structures and anti-neuroinflammatory activity.

Phytochemical investigation on the aerial parts of a Lamiaceous medicinal plant Perovskia scrophulariifolia collected in Uzbekistan resulted in the isolation of two new 20-norabietane diterpenes, along with thirteen known diterpenes including one 20-norabietane, eight abietanes, one 6,7-secoabietane, and three icetexanes. The structures of new 20-norabietane diterpenes, perovsfolins C (1) and D (2), were elucidated by spectroscopic analyses aided with calculations of ECD spectra. Perovsfolin C (1) is the first 20-norabietane diterpene possessing a 1,11-epoxy moiety, while perovsfolin D (2) is a 20-norabitetane diterpene with a 2-hydroxy-1,4-quinone moiety as C-ring. Anti-neuroinflammatory activity of the isolated diterpenes on microglial cells was evaluated.

A comparative study on chemical composition and antimicrobial activity of essential oils from three Phlomis species from Uzbekistan.

Essential oils obtained from the aerial parts of Phlomis bucharica, P. salicifolia and P. sewerzowii were determined using GC-FID and GC-MS methods. A total of 76 components were identified in the three species representing 97.12, 88.34, and 96.41% of the whole oil, respectively. High percentages of thymol (20.41%) and camphor (14.46%) exist in P. bucharica oil. Methyl palmitate predominates in P. salicifolia oil representing 51.15% whereas thymol (35.76%) is the major constituent in P. sewerzowii essential oil. GC-MS analyses showed that P. bucharica and P. sewerzowii are more closely related comparable to P. salicifolia. The antimicrobial activity of the essential oils was assessed against different microorganisms using agar-disc diffusion and broth microdilution assay. Among the three tested species, the essential oil of P. salicifolia showed the highest antibacterial activity.

Comparative study on the chemical composition and biological activities of the essential oils of three Lagochilus species collected from Uzbekistan.

Lagochilus species are mainly distributed in Central Asia and widely used in folk medicine as a sedative and haemostatic. The present investigation reports on the extraction by hydrodistillation and the chemical composition of three Lagochilus species (L. gypsaceus, L. inebrians and L. setulosus) essential oils from Uzbekistan. The chemical composition of these essential oils was determined by GC-MS. The results showed that the studied essential oils are made up mainly of linalool (11.97%), ß-ionone (11.75%), trans-chrysanthenyl acetate (7.15%), α-terpineol (7.40%) for L. gypsaceus; trans-chrysanthenyl acetate (9.40%), eugenol (7.01%), trans-verbenol (3.85%), bicyclo[3.1.1]hept-3-en-2-one (3.76%), pinocarvone (3.43%) for L. inebrians; and finally 2,4-bis(1,1-dimethylethyl)phenol (19.78%), bicyclo[3.1.1]hept-2-en-4-ol (5.43%), hexadecanoic acid (5.39%), limonene (5.19%), 2-hexenal (5.03%) for L. setulosus. The best antioxidant and tyrosinase inhibitory activity was observed for the essential oil of L. inebrians. However, L. setulosus essential oil exhibited the strongest inhibitory effect against amylase.

4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects.

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), ß-sitosterol (6), and ß-sitosterol ß-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki' of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).

C28 Terpenoids from Lamiaceous Plant Perovskia scrophulariifolia: Their Structures and Anti-neuroinflammatory Activity.

Structurally unique C28 terpenoids, perovsfolins A (1) and B (2), were isolated from the aerial parts of an Uzbek medicinal plant, Perovskia scrophulariifolia (Lamiaceae). Their chemical structures including an unprecedented 6/8/6/6/6 pentacyclic carbon skeleton with a C6-C3 ester moiety were elucidated on the basis of spectroscopic analyses aided by density functional theory calculations as well as chemical evidence. Perovsfolin B (2) exhibited an anti-neuroinflammatory activity.