Organoselenium transition metal complexes as promising candidates in medicine area.

The medicinal properties of transition metal complexes are greatly influenced by the nature and physico-chemical features of the ligand present in the complex structure. Due to the unique biological properties of the organoselenium compounds reflected in the variety of pharmacological activities (such as antioxidative, antiviral, antimicrobial and anticancer), the last years have brought increased interest for their use as a ligands compounds in the design and syntheses of range of transition metal-based coordination compounds that have been explored as antitumor and antimicrobial agents. Our aim in this review is to provide the overview of an recent development of the transition metal complexes bearing organoselenium ligands in the structure that could be promising choice for the treatment of various diseases, particularly cancer and infective diseases. For this purpose, the complexes of Co, Ni, Cu, Zn, Ru, Pd, Pt, Au and Sn as the most explored examples will be included and discussed.

Exposure to Stress and Burnout Syndrome in Healthcare Workers, Expert Workers, Professional Associates, and Associates in Social Service Institutions.

Background and Objectives: Workplace burnout syndrome is often as sociated with particular aspects of certain job positions, especially those that entail working with people with special needs. The burnout syndrome in healthcare jobs is a serious problem that has grown into an epidemic among healthcare workers and associates. The aim of this research is to assess the presence of stress and burnout syndrome at work with healthcare workers, expert workers, professional associates, and associates in social service institutions in Belgrade. Materials and Methods: This research was conducted in the form of a cross-sectional study of a representative sample in social institutions in Belgrade. It was conducted from March to the end of June of 2023. The sample of the study had 491 participants. The questionnaires used were a structured instrument with social-demographic and social-economic characteristics, workplace characteristics, lifestyle characteristics, and the following questionnaires: DASS-21, Copenhagen, Brief Resilience Scale, and Brief Resilient Coping Scale. Results: The end results indicate the following to be significant risk factors for the occurrence of workplace burnout syndrome: overtime (OR = 2.62; CI = 1.50-4.56), BRS average score (OR = 0.28; CI = 0.17-0.44), DASS21 D heightened depression (OR = 2.09; CI = 1.1-4.04), DASS21 A heightened anxiety (OR = 2.38; CI = 1.34-4.21), and DASS21 S heightened stress (OR = 2.08; CI = 1.11-3.89). The only protective risk factor that stood out was the self-assessment of health levels (OR = 0.60; CI = 0.42-0.85). Conclusion: Overtime is a significant factor associated with workplace burnout. Apart from it, other significant factors associated with workplace burnout were heightened depression, anxiety, and stress levels.

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.

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.

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.

VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

Antioxidant Extracts of Three Russula Genus Species Express Diverse Biological Activity.

This study explored the biological properties of three wild growing Russula species (R. integra, R. rosea, R. nigricans) from Serbia. Compositional features and antioxidant, antibacterial, antibiofilm, and cytotoxic activities were analyzed. The studied mushroom species were identified as being rich sources of carbohydrates and of low caloric value. Mannitol was the most abundant free sugar and quinic and malic acids the major organic acids detected. The four tocopherol isoforms were found, and polyunsaturated fatty acids were the predominant fat constituents. Regarding phenolic compounds, P-hydroxybenzoic and cinnamic acids were identified in the prepared methanolic and ethanolic extracts, which displayed antioxidant activity through the inhibition of thiobarbituric acid reactive substances (TBARS) formation and oxidative hemolysis; the highest activity was attributed to the R. nigricans ethanolic extract. This is the first report on the antibacterial and antibiofilm potential of the studied species, with the most promising activity observed towards Streptococcus spp. (0.20-0.78 mg/mL as the minimal inhibitory concentration, MIC). The most promising cytotoxic effect was caused by the R. integra methanolic extract on non-small cell lung cancer cells (NCI-H460). Therefore, due to the observed in vitro bioactive properties, the studied mushrooms arise as a source of functional ingredients with potential to be used in novel nutraceutical and drug formulations, which can be used in the treatment of various diseases and health conditions.

HEALTH TECHNOLOGY ASSESSMENT IN CENTRAL-EASTERN AND SOUTH EUROPE COUNTRIES: BOSNIA AND HERZEGOVINA.

OBJECTIVES: The aim of this study was to describe the healthcare system and health financing in Bosnia and Herzegovina and recent trends in health technology assessment (HTA) placement in the system. METHODS: A short review of PubMed published literature has been conducted using key words related to reimbursement, HTA, and health policy. We also revised legislation in Bosnia and Herzegovina published in Official Gazettes related to healthcare financing and organization. RESULTS: A deecentralized system in Bosnia and Herzegovina led to high differences in health policy. HTA has been recognized in legislation in Bosnia and Herzegovina, but it still has not been introduced in practice in full capacity. A small number of publications are found in PubMed treating these issues, but generally the problem of introduction of HTA in Bosnia and Herzegovina is lack of experts, as well as the political environment and education in this field. CONCLUSIONS: HTA in the Federation of Bosnia and Herzegovina and the Republic of Srpska has a short history because of a huge political impact in the decision-making process, decentralized system, and multiple decision makers in these regions. Challenges remain in assessments, in development of more transparent approaches in different areas of the health system in these regions, and in consistent application of appropriate standards especially in education of professionals who will provide establishment of HTA in the health system of The Federation of Bosnia and Herzegovina and the Republic of Srpska.

Antioxidant and anti-inflammatory activity of Potentilla reptans L.

Potentilla species have been used in traditional medicine in the treatment of different ailment, disease or malady. Potentilla reptans (P. reptans) has been scarcely studied. The aim of this study was to test antioxidant and anti-inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory effect was evaluated by experimental animal model of phenol-in-acetone induced mice ear edema. DPPH radical-scavenging activity of both tested extracts was concentration dependent with IC50 values 12.11 µg/mL (aerial part) and 2.57 µg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous extract possesses anti-inflammatory effect and higher antioxidant activity than aerial part.

Novel Insights into Amlodipine-Induced Gingival Enlargement: A Clinical and Molecular Perspective.

This study aimed to identify risk factors for amlodipine-induced gingival enlargement, assess quality of life, and analyze gingival tissue. This cross-sectional study involved hypertensive patients on amlodipine, divided into groups with and without gingival enlargement. Assessments included sociodemographic data, clinical evaluations, and clinical parameters. Quality of life was assessed using OHIP-14 and WB-HRQoL scales. Gingival tissue samples were analyzed for oxidative status and key molecules using RT-PCR and colorimetric assays. The study included 32 patients with no significant sociodemographic differences between groups (p > 0.05). Patients with gingival enlargement had higher systolic blood pressure (139.63 ± 10.743 vs. 128.38 ± 7.249, p = 0.028) and higher OHIP-14 scores. The RT-PCR analysis showed significant differences in IL-6, TNF-α, IL-33, ST2, TGF-ß1, FGF-2, CTGF, VEGF-D, and KGF expression. IL-6, TNF-α, ST2, and FGF-2 expression levels were lower in patients taking amlodipine, with and without gingival enlargement. TGF-ß1 and CTGF expression levels were highest in patients with amlodipine-induced gingival enlargement. SOD activity was also highest in these patients, whereas MDA levels were higher in patients with gingival enlargement without amlodipine. Our study highlights the impact of amlodipine-induced gingival enlargement on oral health and quality of life, emphasizing fibrosis and oxidative stress, and suggests the need for integrated healthcare approaches and further research.

Enhancing Bioactivity of N,N,N-Chelating Rhodium(III) Complexes with Ionic Liquids: Toward Targeted Cancer Therapy.

This study investigates the potential of using ionic liquids as cosolvents to enhance the solubility and activity of poorly soluble rhodium(III) complexes, particularly those with diene, pyridine derivatives, and camphor-derived bis-pyrazolylpyridine ligands, in relation to 5'-GMP, CT-DNA, and HSA as well as their biological activity. Findings indicate that ionic liquids significantly increase the substitution activity of these complexes toward 5'-GMP while only marginally affecting DNA/HSA binding affinities with molecular docking, further confirming the experimental results. Lipophilicity assessments indicated good lipophilicity. Notably, cytotoxicity studies show that Rh2 is selectively effective against HeLa cancer cells, with IL1 and IL10 modulating the cytotoxic effects. Redox evaluations indicate that rhodium complexes induce oxidative stress in cancerous cells while maintaining redox balance in noncancerous cells. By elucidating the role of ionic liquids in modulating these effects, the study proposes a promising avenue for augmenting the efficacy and selectivity of cancer treatments, thus opening new horizons in cancer therapeutics.

Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study.

Schizophrenia is a chronic mental illness with a poor quality of life (QoL). The main aim of this study was to measure the QoL and factors that affect the QoL of patients with schizophrenia placed in a social welfare institution. This cross-sectional study included 287 patients with schizophrenia who were treated in a long-stay social care institution in which QoL was assessed using five different instruments: the World Health Organization Quality of Life scale, the EuroQoL Five-Dimension-Five-Level scale (including the visual analog scale), the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form, and the Brief Psychiatric Rating Scale. To determine the impact of patients' characteristics on score values, multiple linear regression using backward elimination was employed. Due to non-normality in the distribution of the dependent variables, a Box-Cox power transformation was applied to each dependent variable prior to conducting multiple linear regression analysis. Results revealed that patients with schizophrenia have lower QoL. Our study revealed that age, level of education, type of accommodation, type of pavilion, age of onset of the disease, number of prescribed antipsychotics, number of psychiatric comorbidities, duration of therapy, and the number of daily doses of antipsychotics are dominant contributors to the QoL in patients with schizophrenia who were treated in social welfare institution.

Chemical profiles and bioactivities of polyphenolic extracts of Lavandula stoechas L., Artemisia dracunculus L. and Ocimum basilicum L.

This study assessed the chemical profiles and bioactivities of the infusions, decoctions and hydroethanolic extracts of tarragon, basil and French lavender. The extracts were chemically characterised (HPLC-DAD-ESI/MS) and their bioactivities were evaluated in vitro. All extracts revealed antimicrobial, antifungal and antioxidant properties. French lavender extracts showed higher total phenolic content, regardless of the extraction method used, and antioxidant and antitumour capacities, but no anti-inflammatory action. All basil and two of the tarragon extracts revealed anti-inflammatory power. Thus, tarragon, basil and French lavender extracts may be considered for inclusion in foods, as preservatives or functional ingredients. Nonetheless, further studies must be conducted to evaluate the pharmacokinetic parameters of the bioactive compounds.

Risk Factors for Potential Drug-Drug Interactions in Outpatients with Dyslipidemia.

Background: Patients with dyslipidemia are usually multimorbid and require polypharmacy. Therefore, it is important to identify potential drug-drug interactions (pDDIs) in time to prevent their consequences. We aimed to identify and analyze risk factors contributing to their occurrence to guide health professionals. Methods: A prospective cross-sectional study of 216 outpatients with dyslipidemia was conducted from May 2021 to April 2022 in Podgorica, the capital of Montenegro. pDDIs were identified using Medscape, Epocrates, and Drugs online interaction checkers. Multivariate regression analysis was performed to evaluate the potential predictors of interactions. Results: pDDIs were detected in 212 (98.1%) participants, whereas pDDIs with high clinical significance were detected in 25.46%, 40.74%, and 58.8% of subjects by Drugs, Epocrates, and Medscape, respectively. Polypharmacy emerged as a risk factor for the occurrence of pDDIs in all three checkers in each category of clinical significance. The use of non-steroidal anti-inflammatory drugs and antiplatelet drugs contributes to the incidence of severe pDDIs B=1.014, 95%CI 0.681-1.346, P=0.000 and B=0.492, 95%CI 0.286-0.698, P=0.000, by Epocrates and Medscape respectively. The number of prescribers per patient was a protective factor against moderate pDDI B= -0.858, 95%CI -1.572-(-0.144), P=0.019 and B= -0.956, 95%CI -1.671-(-0.241), P=0.009, by Medscape and Epocrates, respectively, but a risk factor for the occurrence of minor pDDIs B=0.373, 95%CI 0.033-0.712 P=0.032 and B=0.143, 95%CI 0.042-0.244, P=0.006, by the same checkers. Conclusion: Knowledge of the risk factors contributing to the occurrence of pDDIs is important for the development and implementation of strategies for their prevention, and given the high prevalence of dyslipidemia, understanding these factors seems crucial nowadays.

Synthesis and Antioxidant Properties of Organoselenium Compounds.

BACKGROUND: The chemistry of organoselenium reagents provides an asset for organic synthesis. The versatility of these reagents as electrophiles and nucleophiles makes them one of the key components of organic synthesis. Various synthetic transformations such as oxyselenenylations, selenocyclization and selenoxide elimination have been successfully achieved using organoselenium reagents under mild reaction conditions. The presence of selenocysteine in a few mammalian enzymes was the key information for selenium chemists to explore the biochemistry of selenium compounds. Glutathione peroxidase (GPx), a mammalian selenoenzyme, is well known for maintaining redox equilibrium by detoxifying reactive oxygen species. OBJECTIVE: The aim is to critically analyze the recent development and prospects of synthesis and antioxidant properties of organoselenium compounds. METHODS: In this review, we summarised research and review papers from the PubMed and Scopus databases. The primary themes were linked to the synthesis of organoselenium compounds and their capacity to maintain cellular redox equilibrium when exposed to oxidative stress. RESULTS: The study reveals that diselenide compounds synthesised by various methods showed a better antioxidant activity profile compared to selenides. In a few cases, the activity was found better than the standard compound ebselen. Moreover, the synthesis and antioxidant activity of Selenium-based nanoparticles have been also included. CONCLUSION: In the past two decades, various biological properties of organoselenium compounds have been extensively studied, including the antioxidant properties. This review article will give insight into the synthesis of different types of recently synthesised organoselenium compounds. The review would be helpful to the researchers working in the field of medicinal chemistry in directing the synthesis of new organoselenium compounds as antioxidants.

Natural extracts against agricultural pathogens: A case study of Celtis australis L.

Plant extracts and other plant products have been used as an alternative to synthetic fungicides or an additional way to reduce their use. The choice of plant extracts and their application depends on their functional characteristics, availability, cost-effectiveness, and their impact on phytopathogens, and also on the environment. Therefore, the present study aims to assess the potential of Celtis australis methanolic extracts as source of compounds with antifungal activity. Methanolic extracts prepared from leaves and unripe mesocarps of C. australis collected from different localities of Montenegro (Podgorica-PG, Donja Gorica-DG, and Bar-BR) were evaluated for their phenolic compounds' composition as well as antifungal and cytotoxic properties. Obtained results revealed that extracts contain various bioactive constituents including phenolic acids, flavonoids, and their derivatives. The predominant phenolic acid was ferulic acid, identified in leaf samples from DG (187.97 mg/100 g dw), while isoorientin was the most abundant phenolic compound found in all examined samples. Regarding antifungal potential of the tested samples, all but one (prepared from mesocarp BR) possessed higher activity than Previcur, a commercial systemic fungicide intended to control seedlings. In vitro studies on HaCaT cell line showed that the extracts had no toxic effect toward the tested cell line. These results lead to the conclusion that methanolic extracts of C. australis can become an alternative to the use of synthetic fungicides in agriculture. Those extracts represent natural biodegradable fungicides and enable more efficient control of pathogenic fungi.

Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review.

OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.

Upcycling Quince Peel into Bioactive Ingredients and Fiber Concentrates through Multicomponent Extraction Processes.

This study aimed to promote the total upcycling of quince (Cydonia oblonga Mill.) peel into bioactive extracts (BEs) and fiber concentrates (FCs). The multicomponent extraction processes were optimized using response surface methodology (RSM) coupled with a 20-run experimental design, where the effects of time (1-120 min), temperature (25-95 °C), and EtOH percentage (0-100%) were combined. In addition to the extraction yields, BEs were analyzed for phenolic compounds, organic acids, and other water-soluble constituents, while FCs were characterized for their color and dietary fiber content. Statistically valid theoretical models were obtained by fitting these dependent variables to a quadratic equation and used to predict optimal extraction conditions. Those obtained for phenolic compounds and malic acid were experimentally validated, yielding 9.3 mg/g and 7.6 g/100 g of these bioactive constituents, respectively, and about 51% (w/w) FC. These BEs showed in vitro antioxidant activity and antimicrobial effects against foodborne fungi and bacteria, standing out in some aspects in relation to synthetic food additives, mainly the malic acid-enriched BE. Overall, the developed extraction processes allowed valorizing of quince peel in FCs and BEs that could be used as natural fortifiers or preservatives in the formulation of foods, beverages and dietary supplements.

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).

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.