Solvent System-Guided Extraction of Centaurium spicatum (L.) Fritch Provides Optimized Conditions for the Biological and Chemical Characteristics of the Herbal Extracts.

Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.

Plant Flavonoids as Reservoirs of Therapeutics against Microbial Virulence Traits: A Comprehensive Review Update.

Flavonoids are secondary metabolites abundantly present in plants and, in most cases, essential contributors to plants bioactivity. They have been studied so far for a range of possible health-beneficial effects, including antioxidant, cardioprotective, and cytotoxic. Therefore, there are data on the antimicrobial potential of a significant number of flavonoids. However, less is known regarding their antivirulence traits. Trending antimicrobial research worldwide has pointed out the promising effects of antimicrobial strategies based on the antivirulence principle, so this review aims to present the newest research regarding the antivirulence effects of flavonoids. Articles on antivirulence flavonoids published from 2015 until now were selected. A range of molecules from this class has been studied up to date, with the most abundant data for quercetin and myricetin, while the most studied organism is Pseudomonas aeruginosa. The antivirulence attributes studied included antibiofilm assessment, followed by data on the inhibition of virulence pigments (pyocyanin, violacein, and staphyloxanthin) and virulence enzyme production (such as sortase A and elastase). Less information is collected on the inhibition of morphological transition, motility, and molecular mechanisms underlying the antivirulence properties of flavonoids and in vivo research. Flavonoids are a group of compounds with a wide range of antivirulence traits and might be further developed into essential parts of novel antimicrobial strategies.

Purple tea: chemical characterization and evaluation as inhibitor of pancreatic lipase and fat digestion in mice.

A variety of the classic green tea plant, Camellia sinensis, was developed and is exclusive to Kenya. Due to high content of anthocyanin polyphenols in its leaves, the beverage obtained from this variety is purple in color and is the origin of the name purple tea. This work had two main purposes. The first one was to identify and quantify the major anthocyanin polyphenols in a hot water aqueous extract of the purple tea leaves. The second one was to test the hypothesis if this extract is capable of inhibiting triglyceride absorption considering that anthocyanin polyphenolics have been frequently associated to antilipidemic effects. Parallel experiments were always done with a similar green tea extract for comparison purposes. The antioxidant, anti-inflammatory, and cytotoxic activities of both tea varieties are similar. The purple tea extract, however, was strongly inhibitory toward the pancreatic lipase (minimal IC50 = 67.4 µg mL-1), whereas the green tea preparation was a weak inhibitor. Triglyceride digestion in mice was inhibited by the purple tea extract starting at 100 mg kg-1 dose and with a well-defined dose dependence. Green tea had no effect on triglyceride digestion at doses up to 500 mg kg-1. The latter effect is probably caused by several components in the purple tea extract including non-anthocyanin and anthocyanin polyphenols, the first ones acting solely via the inhibition of the pancreatic lipase and the latter by inhibiting both the lipase and the transport of free fatty acids from the intestinal lumen into the circulating blood. The results suggest that the regular consumption of Kenyan purple tea can be useful in the control of obesity.

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents-In Silico and In Vitro Evaluation.

Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate derivatives. All tested compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin as well as streptomycin by 10-50 fold. The most sensitive bacterium was En. Cloacae, while E. coli was the most resistant one, followed by M. flavus. The most active compound appeared to be compound 8 with MIC at 0.004-0.03 mg/mL and MBC at 0.008-0.06 mg/mL. The antifungal activity of tested compounds was good to excellent with MIC in the range of 0.004-0.06 mg/mL, with compound 15 being the most potent. T. viride was the most sensitive fungal, while A. fumigatus was the most resistant one. Docking studies revealed that the inhibition of E. coli MurB is probably responsible for their antibacterial activity, while 14a-lanosterol demethylase of CYP51Ca is involved in the mechanism of antifungal activity. Furthermore, drug-likeness and ADMET profile prediction were performed. Finally, the cytotoxicity studies were performed for the most active compounds using MTT assay against normal MRC5 cells.

A Comparative Study of Lactarius Mushrooms: Chemical Characterization, Antibacterial, Antibiofilm, Antioxidant and Cytotoxic Activity.

Mushrooms are valued worldwide for their nutritional, organoleptic and chemical properties. The aim of this study was to determine the chemical composition (free sugars, organic acids, fatty acids, tocopherols and phenolic compounds) and bioactivity of three wild mushrooms (Lactarius piperatus, Lactarius quietus and Lactarius vellereus) from Serbia. Chemical analysis was performed with HPLC-RI and UFLC-PDA (for hydrophilic compounds) and with GC-FID and HPLC-FP (for lipophilic compounds). The analysis of phenolic compounds was performed by UFLC-DAD. Biological activities were evaluated using three different assays (microdilution, TBARS and SRB assays). The results showed that the fruiting bodies were rich in mannitol and trehalose. The main organic acids were oxalic acid and citric acid. As for lipophilic components, stearic, oleic and linoleic acids and ß-tocopherol dominated in all the species studied. In addition, the methanolic and ethanolic extracts obtained showed antibacterial, antibiofilm and antioxidant properties. As for cytotoxicity, the extracts were not toxic or only moderately toxic toward different tumor cell lines. According to the results, the selected Serbian mushrooms are a rich source of bioactive compounds, and due to their good biological potential, they can be further exploited as functional ingredients beneficial to human health (antimicrobial agents, antioxidants).

Light conditions affect the growth, chemical composition, antioxidant and antimicrobial activities of the white-rot fungus Lentinus crinitus mycelial biomass.

The mycelial biomass of basidiomycetes is a promising source of compounds and represents an alternative for industrial and biotechnological applications. Fungi use light as information and hold photoresponse mechanisms, in which sensors respond to light wavelengths and regulate various biological processes. Therefore, this study aimed to investigate the effects of blue, green, and red lights on the growth, chemical composition, and antioxidant and antimicrobial activity of Lentinus crinitus mycelial biomass. The chemical composition of the mycelial biomass was determined by chromatographic methods, antioxidant activity was analyzed by in vitro assays, and antimicrobial activity was investigated by the microdilution assay. The highest mycelial biomass yield was observed under blue-light cultivation. Many primordia arose under blue or green light, whereas the stroma was formed under red light. The presence of light altered the primary fungal metabolism, increasing the carbohydrate, tocopherol, fatty acid, and soluble sugar contents, mostly mannitol, and reducing the protein and organic acid concentrations. Cultivation under red light increased the phenol concentration. In contrast, cultivation under blue and green lights decreased phenol concentration. Benzoic and gallic acids were the main phenolic acids in the hydroalcoholic extracts, and the latter acids increased in all cultures under light, especially red light. Mycelial biomass cultivated under red light showed the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The ferric reducing antioxidant power (FRAP) method showed that all light wavelengths increased the antioxidant activity of mycelial biomass, with the highest value under red light. Moreover, the ß-carotene/linoleic acid co-oxidation (BCLA) assay demonstrated that the antioxidant activity was affected by light cultivation. Mycelial biomass grown under all conditions exhibited antibacterial and antifungal activities. Thus, mycelial biomass cultivation of L. crinitus under light conditions may be a promising strategy for controlling the mycelial chemical composition and biomass yield.

Analysis of Tonsil Tissues from Patients Diagnosed with Chronic Tonsillitis-Microbiological Profile, Biofilm-Forming Capacity and Histology.

Chronic tonsillitis (CT) is a global health issue which can impair patient's quality of life and has an important socioeconomic impact due to the nonrational use of antibiotics, increased antimicrobial resistance and frequent need for surgical treatment. In order to isolate and identify the causing agents of CT, a total of 79 postoperative palatine and adenoid tissue samples were obtained from the ENT Clinic, KBC Zvezdara, Belgrade, Serbia. Culture identification was performed by MALDI-TOF MS and the Staphylococcus aureus isolates were tested for biofilm forming capability and antibiotic susceptibility. Additionally, a histological examination of palatine and adenoid tissue was performed in order to detect the presence of CT-causing bacteria. The slight majority of participants were females with median age of 28 years for adult patients (group I) and 6 years for children (group II). Analysis of the incidence of bacteria isolated from tissue samples in both groups showed the highest prevalence of S. aureus, Streptococcus oralis and Streptococcus parasanquinis. In addition to interfollicular hyperplasia, colonies of species S. aureus were detected in histological material. The presence of biofilm might be the reason for the recurrence of infection. Therefore, searching for a new treatment of CT is of great importance.

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents.

In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound 2j was found to be the most potent (MIC/MBC at 0.23-0.94 mg/mL and 0.47-1.88 mg/mL) On the other hand, compounds showed good antifungal activity (MIC/MFC at 0.06-0.47 and 0.11-0.94 mg/mL respectively) with 2d being the most active one. The docking studies revealed that inhibition of E. coli MurB and 14-lanosterol demethylase probably represent the mechanism of antibacterial and antifungal activities.

Synthesis and Antimicrobial Activity of New Heteroaryl(aryl) Thiazole Derivatives Molecular Docking Studies.

Herein, we report the design, synthesis, and evaluation of the antimicrobial activity of new heteroaryl (aryl) thiazole derivatives. The design was based on a molecular hybridization approach. The in vitro evaluation revealed that these compounds demonstrated moderate antibacterial activity. The best activity was achieved for compound 3, with MIC and MBC in the range of 0.23-0.7 and 0.47-0.94 mg/mL, respectively. Three compounds (2, 3, and 4) were tested against three resistant strains, namely methicillin resistant Staphylococcus aureus, P. aeruginosa, and E. coli, which showed higher potential than the reference drug ampicillin. Antifungal activity of the compounds was better with MIC and MFC in the range of 0.06-0.47 and 0.11-0.94 mg/mL, respectively. The best activity was observed for compound 9, with MIC at 0.06-0.23 mg/mL and MFC at 0.11-0.47 mg/mL. According to docking studies, the predicted inhibition of the E. coli MurB enzyme is a putative mechanism of the antibacterial activity of the compounds, while inhibition of 14a-lanosterol demethylase is probably the mechanism of their antifungal activity.

Hesperetin-Between the Ability to Diminish Mono- and Polymicrobial Biofilms and Toxicity.

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it's inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (<50% inhibition with MIC 4 mg/mL). Establishment of polymicrobial C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC50 0.340 mg/mL) and in brine shrimp lethality assay (LC50 > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.

Synthetic and Natural Antifungals-Desirable and Hazardous Effects.

The increasing incidence of patients struggling with fungal infections, along with high losses in the production of different foods/crops due to fungal diseases presents a significant burden to healthcare, agronomy, and economies worldwide [...].

Bioactive Compounds and Functional Properties of Herbal Preparations of Cystus creticus L. Collected From Rhodes Island.

The members of Cystus genus are perenial shrubs with a well-established use in traditional medicine. Among these, C. creticus is the most popular, herbal preparations obtained from its aerial parts being recognized as antimicrobial, antitumor and anti-inflammatory agents. The present study aimed to evaluate phytochemical profile and bioactive potential of aqueous and hydroethanolic extracts of C. creticus aerial parts harvested from two different areas of Rhodes island. LC-DAD-ESI/MSn analysis revealed the presence of myricetin and quercetin glycosides as main compounds, especially in aqueous extracts, being probably responsible for their enhanced antioxidant and antimicrobial potential. On the other side, hydroethanolic preparations exerted a strong anti-inflammatory and anti-biofilm activity. Our findings suggest that the use of solvents with intermediate polarity can assure the best recovery of bioactive compounds from C. creticus, increasing the extraction yield for other non-phenolic compounds which can enhance therapeutic potential of the extract through a synergistic action.

Phlomis fruticosa L. exerts in vitro antineurodegenerative and antioxidant activities and induces prooxidant effect in glioblastoma cell line.

Despite the significant advances in drug development we are witnessing the inability of health systems to combat both neurodegenerative diseases and cancers, especially glioblastoma. Hence, natural products are comprehensively studied in order to provide novel therapeutic options. This study aimed to explore anti-neurodegenerative and anti-glioblastoma potential of extract of Phlomis fruticosa L. using in vitro model systems. It was found that the methanol extract of P. fruticosa was able to efficiently reduce activities of enzymes linked to neurodegenerative disease including acetylcholinesterase, butyrylcholinesterase and tyrosinase. Furthermore, P. fruticosa extract has shown excellent antioxidant potential, as evidenced by six different methods. Analysis of cytotoxic effect of P. fruticosa extract on A172 glioblastoma cell line revealed that the concentration of the extract necessary for 50 % inhibition of A172 growth (IC50) was 710 µg/mL. The extract did not induce changes in proliferation and morphology of A172 glioblastoma cells. On the other side, production of ROS was increased in A172 cells treated with the extract. Observed cytotoxic effect of P. fruticosa extract might be based on increase in ROS generation upon treatment. Quantitative chemical analysis revealed the presence of twelve different polyphenols with the cis 3-O-caffeoylquinic acid being the most abundant. This study provided scientific evidence for further exploration of P. fruticosa as a promising natural anti-neurodegenerative therapeutic option.

Thiazolidin-4-Ones as Potential Antimicrobial Agents: Experimental and In Silico Evaluation.

Herein, we report computational and experimental evaluations of the antimicrobial activity of twenty one 2,3-diaryl-thiazolidin-4-ones. All synthesized compounds exhibited an antibacterial activity against six Gram-positive and Gram-negative bacteria to different extents. Thus, the MIC was in the range of 0.008-0.24 mg/mL, while the MBC was 0.0016-0.48 mg/mL. The most sensitive bacterium was S. Typhimurium, whereas S. aureus was the most resistant. The best antibacterial activity was observed for compound 5 (MIC at 0.008-0.06 mg/mL). The three most active compounds 5, 8, and 15, as well as compound 6, which were evaluated against three resistant strains, MRSA, P. aeruginosa, and E. coli, were more potent against all bacterial strains used than ampicillin. The antifungal activity of some compounds exceeded or were equipotent with those of the reference antifungal agents bifonazole and ketoconazole. The best activity was expressed by compound 5. All compounds exhibited moderate to good drug-likeness scores ranging from -0.39 to 0.39. The docking studies indicated a probable involvement of E. coli Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds. Finally, the assessment of cellular cytotoxicity of the compounds in normal human MRC-5 cells revealed that the compounds were not toxic.

Polyphenols as Inhibitors of Antibiotic Resistant Bacteria-Mechanisms Underlying Rutin Interference with Bacterial Virulence.

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin's ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI, lasR, rhlI, rhlR, pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials.

Emerging Antifungal Targets and Strategies.

Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.

BACKGROUND: Infectious diseases represent a significant global strain on public health security and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains. METHODS: Compounds were synthesized using the classical organic chemistry methods. Prediction of biological activity spectra was carried out using PASS and PASS-based web applications. Pharmacophore modeling in LigandScout software was used for quantitative modeling of the antibacterial activity. Antimicrobial activity was evaluated using the microdilution method. AutoDock 4.2® software was used to elucidate probable bacterial and fungal molecular targets of the studied compounds. RESULTS: All compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Three compounds were tested against resistant strains MRSA, P. aeruginosa and E. coli and were found to be more potent than MRSA than reference drugs. All compounds demonstrated a higher degree of antifungal activity than the reference drugs bifonazole (6-17-fold) and ketoconazole (13-52-fold). Three of the most active compounds could be considered for further development of the new, more potent antimicrobial agents. CONCLUSION: Compounds 5b (Z)-3-(3-hydroxyphenyl)-5-((1-methyl-1H-indol-3-yl)methylene)-2-thioxothiazolidin-4-one and 5g (Z)-3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-benzoic acid as well as 5h (Z)-3-(5-((5-methoxy-1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)benzoic acid can be considered as lead compounds for further development of more potent and safe antibacterial and antifungal agents.

Biochemical and Molecular Profiling of Wild Edible Mushrooms from Huila, Angola.

The harvesting, processing, and sale of wild edible mushrooms (WEM) is a relevant economic activity in Angola and a good example of the use of non-wood forest products for food. Although there is deep traditional knowledge about the general properties of WEMs, a huge gap remains in detailed scientific knowledge. Thus, this study aimed to investigate the socio-economic importance of the species sold at local markets in Huila, Angola, from their molecular identification to the assessment of their nutritional, chemical, and bioactive profiles. From the eight WEM morphotypes studied, five were identified based on phenotypical and molecular approaches (four Russula spp., and Amanita loosei). The studied mushrooms proved to be a rich source of carbohydrates, proteins, and ashes, also presenting low amounts of fat. Chemical analyses further revealed mannitol as the main free sugar in all samples, and organic acids, namely, oxalic, quinic, malic, citric, and fumaric acids in low amounts. Additionally, the α-tocopherol isoform and monounsaturated fatty acids were predominant. Regarding phenolic acids, protocatechuic, p-hydroxybenzoic, p-coumaric, and cinnamic acids were detected in all mushroom hydroethanolic extracts, being responsible for their antioxidant, antibacterial, and antifungal activities. Our investigation contributes to the identification and knowledge of WEMs as important complementary food sources in Angola, some of which were reported for the first time, promoting their utilization as a basis of nutritional and functional ingredients, as being able to be part of a balanced diet and to be used in new bio-based formulations.

4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation.

This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (-) bacteria revealed that the MIC of indole derivatives is in the range of 0.06-1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47-1.88 mg/mL. S. aureus appeared to be the most resistant strain, while S. Typhimurium was the most sensitive. Compound 5x was the most promising, with an MIC in the range of 0.06-0.12 mg/mL, followed by 5d and 5m. An evaluation of these three compounds against resistant strains, namely MRSA P. aeruginosa and E. coli, revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds 5m and 5x were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds 5d, 5m, and 5x interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound 5g. Drug likeness scores of compounds was in a range of -0.63 to 0.29, which is moderate to good. According to docking studies, E. coli MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells.

Comprehensive Biological and Chemical Evaluation of Two Seseli Species (S. gummiferum and S. transcaucasicum).

Seseli L. is one of the largest genera of the Apiaceae family widely known for their traditional uses as herbal remedies. In the present study, the methanolic and water extracts of two Seseli species, S. gummiferum and S. transcaucasicum were evaluated for their bioactive contents and biological activities. The total phenolic and flavonoid contents in the extracts ranged from 19.09 to 24.33 mg GAE/g and from 0.45 to10.09 mg RE/g, respectively. Moreover, while narcissin was detected as the most abundant component in the methanolic extract of S. transcaucasicum (261.40 µg/g), chlorogenic acid was identified as the major component in all the other extracts, although a high amount was also present in the methanolic S. transcaucasicum extract (107.48-243.12 µg/g). The total antioxidant capacity was also determined by the phosphomolybdenum assay (0.66-1.18 mM TE/g). Other antioxidant assays such as the radical scavenging assays (DPPH: 5.51-11.45 mg TE/g; ABTS: 43.46-51.91 mg TE/g), reducing assays (CUPRAC: 41.67-53.20 mg TE/g; FRAP: 31.26-34.14 mg TE/g), as well as the metal chelating activity assay (14.38-38.57 mg EDTAE/g) were conducted. All the extracts showed inhibitory potential against the enzyme's amylase (0.12-0.78 mM ACAE/g), acetyl- and butyryl-cholinesterase (0.15-9.71 mg GALAE/g), while only the methanolic extracts acted as inhibitors of tyrosinase (107.15 and 109.37 mg KAE/g) and only the water extract of S. gummiferum displayed anti-glucosidase activity (0.13 mM ACAE/g). Interestingly, the methanolic extracts of both Seseli species showed lower cytotoxicity towards HaCaT cells (IC50: >500 µg/mL), compared to the water extracts (IC50: 267.8 and 321.41 µg/mL). Besides, only the methanolic extracts showed a slight wound healing effect (28.21 and 31.23%). All extracts showed antibacterial action against Staphylococcus lugdunensis (minimum inhibitory and bactericidal concentrations: 0.025-2 mg/mL). S. gummiferum methanolic extract, which exhibited the highest antibacterial potency was found to inhibit adhesion and invasion of S. lugdunensis to HaCaT cells as well. Taken together, this study demonstrated the two Seseli species to harbour interesting bioactive components, in particular polyphenolics and to exhibit several biological properties that could be further investigated for their potential exploitation as healing agents as supported by various traditional medicinal uses.