Dietary lipids management: are there any benefits from the prevention and treatment of 4T1 murine breast carcinoma?

This study investigated the effect of vegetable and fish oils with different n-3 / n-6 PUFAS ratios on the lipoprotein profile and on the development of murine breast cancer 4T1. Female Balb/c mice (6-7 weeks) received diets containing 4.0% fat during seven weeks. On the fourth week, animals were inoculated into the posterior left flank with 2.5 × 106 4T1 cells. Body weight and food intake were registered and the profile serum lipoproteins was determined. Tumor volume, histopathological and immunohistochemical studies, myeloperoxidase and N-acetylglucosaminidase activities, TNF-α, hemoglobin and VEGF levels were analysed. The highest n-3 / n-6 ratio was found in fish oil (15.8:1), followed by linseed (2.4:1), canola (1:2.1) and soybean (1:9.4) oils. Body weight, food and caloric intake, lipoprotein profile, tumor weight, tumor evolution and histopathological analysis were not different. Canola oil increased cell proliferation when compared to soybean oil, and fish oil changed the inflammatory response and increased VEGF in tumors compared to other groups. The type of fatty acid and the high ratio of n-3 / n-6 PUFAs in the diet influenced cell proliferation and inflammation in the tumor differentially, highlighting the increase of neutrophils and VEGF levels in animals fed on fish oil.

Alternative protein sources of plant, algal, fungal and insect origins for dietary diversification in search of nutrition and health.

This review aimed to compare alternative protein sources in terms of nutritional composition and health benefits with the purpose of disseminating up-to-date knowledge and contribute for diversification of the food marked and consumers decision-making. Plant-based is the most well-established category of alternative proteins, but there is still room for diversification. Less conventional species such as chia seeds are prominent sources of ω-3 (∼60% total lipids), while hempseed and quinoa are notable sources of ω-6 (up to 58% and 61%, respectively). Edible insects and microalgae are alternative foods rich in protein (up to 70%), fibers (∼30%), as well as peptides and polysaccharides with antimicrobial, antioxidant, anti-hypertensive, antidiabetic, antidepressant, antitumor, and immunomodulatory activities. Additionally, lipid contents in insect larvae can be as high as 50%, on a dry weight basis, containing fatty acids with anti-inflammatory and antitumor properties. In contrast, edible fungi have low lipid contents (∼2%), but are rich in carbohydrates (up to 79%) and have balanced amino acid profiles. The results suggest that food formulations combining different alternative protein sources can meet dietary requirements. Further studies on flavoring and texturing processes will help to create meat and dairy analogs, thus helping to broaden acceptance and applicability of alternative protein sources.

Nutritional Quality, Techno-Functional Characteristics, and Safety of Biomass Powder and Protein Isolate Produced from Penicillium maximae.

This study investigated the suitability of Penicillium maximae biomass powder and protein isolate as a food product or food ingredient. The biomass powder is rich in proteins (34.8%) and insoluble fiber (36.2%) but poor in lipids (3.1%). Strong water hydration (8.3 g/g, 8.5 g/g) and oil holding (6.9 g/g, 16.3 g/g) capacity were observed in the biomass powder and protein isolate, respectively, besides 100% emulsion stability, indicating multiple applications in the food industry. No locomotor impairment was induced in Drosophila melanogaster flies after consuming extracts of P. maximae biomass powder. Furthermore, decreased production of reactive oxygen species and preservation of survival, viability, and fertility parameters were observed in the nematode Caenorhabditis elegans, which reinforces the potential of P. maximae biomass for human and animal consumption. Together, the results show the vast food applicability of P. maximae biomass and protein isolate as protein substitutes with several health and environmental benefits.

Recent Findings in Azaphilone Pigments.

Filamentous fungi are known to biosynthesize an extraordinary range of azaphilones pigments with structural diversity and advantages over vegetal-derived colored natural products such agile and simple cultivation in the lab, acceptance of low-cost substrates, speed yield improvement, and ease of downstream processing. Modern genetic engineering allows industrial production, providing pigments with higher thermostability, water-solubility, and promising bioactivities combined with ecological functions. This review, covering the literature from 2020 onwards, focuses on the state-of-the-art of azaphilone dyes, the global market scenario, new compounds isolated in the period with respective biological activities, and biosynthetic pathways. Furthermore, we discussed the innovations of azaphilone cultivation and extraction techniques, as well as in yield improvement and scale-up. Potential applications in the food, cosmetic, pharmaceutical, and textile industries were also explored.

Use of the Versatility of Fungal Metabolism to Meet Modern Demands for Healthy Aging, Functional Foods, and Sustainability.

Aging-associated, non-transmissible chronic diseases (NTCD) such as cancer, dyslipidemia, and neurodegenerative disorders have been challenged through several strategies including the consumption of healthy foods and the development of new drugs for existing diseases. Consumer health consciousness is guiding market trends toward the development of additives and nutraceutical products of natural origin. Fungi produce several metabolites with bioactivity against NTCD as well as pigments, dyes, antioxidants, polysaccharides, and enzymes that can be explored as substitutes for synthetic food additives. Research in this area has increased the yields of metabolites for industrial applications through improving fermentation conditions, application of metabolic engineering techniques, and fungal genetic manipulation. Several modern hyphenated techniques have impressively increased the rate of research in this area, enabling the analysis of a large number of species and fermentative conditions. This review thus focuses on summarizing the nutritional, pharmacological, and economic importance of fungi and their metabolites resulting from applications in the aforementioned areas, examples of modern techniques for optimizing the production of fungi and their metabolites, and methodologies for the identification and analysis of these compounds.

Acetylcholinesterase inhibition and antimicrobial activity of hydroxyl amides synthesized from natural products derivatives.

Thirteen natural products derivatives of hydroxyl amide class, three described for the first time, were synthesized by reaction of three indole acids and 3,4,5-trimethoxybenzoic acid with six different amino alcohols in the presence of triphenylphosphine and N-bromosuccinimide. The derivatives were tested against the Gram (+) bacteria Staphylococcus aureus and Bacillus cereus, Gram (-) Pseudomonas aeruginosa and Escherichia coli, besides the yeast Candida albicans. One of the compounds (7) was selectively active against C. albicans (91.3 ± 0.49% inhibition) showing a great potential as a new drug lead, since it was more active than the positive control, miconazole (88.7 ± 2.41% inhibition). Regarding bacterial inhibition, compounds demonstrated mild activity, but inhibition of compounds 9, 10 and 13 towards E. coli is of interest since it is difficult to find drugs selectively active against Gram (-) bacteria. Most of the compounds were very active in the acetylcholinesterase inhibition assay. Compound 7 was again the most active (93.2 ± 4.47%), being more potent than the control galantamine (90.3 ± 0.45%). The most active gallic acid derivatives, compounds 3, 7 and 8 have in common, besides gallic acid skeleton, a (CH2)2OH group, which may be one of the structural requirements for AChE inhibition.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus.

The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7ß-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-ß-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

Maytenus distichophylla and Salacia crassifolia: source of products with potential acetylcholinesterase inhibition

ABSTRACT The phytochemical study of the extract leaves from Maytenus distichophylla Mart. and Salacia crassifolia (Mart. ex Schult.) G. Don, Celastraceae, resulted in the isolation of 3-oxofriedelane, 3β-hydroxyfriedelane, 3β,24-dihydroxyfriedelane, 3-oxo-28,29-dihydroxyfriedelane, two mixtures of pentacyclic triterpenes (α-amyrin with β-amyrin and 3β-stearyloxy-urs-12-ene with 3β-stearyloxy-olean-12-ene), 3β-palmityloxy-urs-12-ene, the steroid β-sitosterol and its glycosylated derivative β-glucosyl-β-sitosterol, tritriacontanoic acid and the natural polymer gutta percha. The chemical structures of these constituents were established by IR, 1H and 13C NMR spectral data. Crude extracts, the mixtures of triterpenes and the isolated constituents were subjected to in vitro acetylcholinesterase inhibitory evaluation. Acetylcholinesterase inhibitory effect was observed for crude chloroform extract leaves from M. distichophylla (100%) and S. crassifolia (97.93 ± 5.63%) and for the triterpenes 3β,24-dihydroxyfriedelane (99.05 ± 1.12%), 3-oxo-28,29-dihydroxyfriedelane (90.59 ± 3.76%) and 3β-palmityloxy-urs-12-ene (97.93 ± 1.47%). The percent inhibitions induced by these natural products were very similar to those produced by physostigmine (93.94 ± 2.10%) a standard acetylcholinesterase inhibitor. Therefore, these results open perspectives for the use of these species as source of compounds with similar physostigmine pharmacological effect.

The formation of sesquiterpenoid presilphiperfolane and cameroonane metabolites in the Bcbot4 null mutant of Botrytis cinerea.

Botrytis cinerea is a polyphagous fungal parasite which causes serious damage to more than 200 plant species and consequent economic losses for commercial crops. This pathogen produces two families of phytotoxins, the botryanes and botcinins, which are involved in the infection mechanism. The B. cinerea genome has provided a complete picture of the genes involved in the biosynthesis of its secondary metabolites. The botrydial biosynthetic gene cluster has been identified. This cluster consists of seven genes, where the genes BcBOT1, BcBOT3 and BcBOT4 encode three mono-oxygenases. A study of the Bcbot4Δ null mutant revealed that this mono-oxygenase was involved in the hydroxylation at C-4 of the probotryane skeleton (C-11 of the presilphiperfolane skeleton). A detailed study of the Bcbot4Δ null mutant has been undertaken in order to study the metabolic fate of the presilphiperfolan-8-ol intermediate biosynthesized by this organism and in particular by this strain. As a result three new presilphiperfolanes and three new cameroonanes have been identified. The results suggest that the absence of the oxygen function at C-11 of the presilphiperfolane skeleton permits rearrangement to a cameroonane whilst hydroxylation at C-11 precludes this rearrangement. It is possible that the interactions of the C-11 hydroxylated derivatives perturb the stereo-electronic requirements for the migration of the C-11:C-7 sigma bond to C-8.

Psychotria viridis: Chemical constituents from leaves and biological properties.

The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and ß-sitosterol; the glycosylated steroids 3-O-ß-D-glucosyl-ß-sitosterol and 3-O-ß-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-ß-D-glucosyl-ß-sitosterol and 3-O-ß-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

Psychotria viridis: Chemical constituents from leaves and biological properties

ABSTRACT The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

Cytotoxic and antimicrobial effects of indium(iii) complexes with 2-acetylpyridine-derived thiosemicarbazones.

Complexes [In(2Ac4oClPh)Cl2(MeOH)] (1), [In(2Ac4pFPh)Cl2(MeOH)] (2), [In(2Ac4pClPh)Cl2(MeOH)] (3) and [In(2Ac4pIPh)Cl2(MeOH)] (4) were obtained with N(4)-ortho-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4oClPh), N(4)-para-fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pFPh), N(4)-para-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pClPh) and N(4)-para-iodophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pIPh). Theoretical studies suggested that the coordinated methanol molecule can be easily replaced by DMSO used in the preparation of stock solutions, with the formation of [In(L)Cl2(DMSO)] (HL = thiosemicarbazonate ligand), and that the replacement of DMSO by water is unfavorable. However, for all complexes the displacement of one or two chloride ligands by water in aqueous solution is extremely favorable. The cytotoxic activity of the compounds was evaluated against HL-60, Jurkat and THP-1 leukemia and against MDA-MB-231 and HCT-116 solid tumor cell lines, as well as against Vero non-malignant cells. The cytotoxicity and selectivity indexes (SI) increased in several cases for the indium(iii) complexes in comparison with the free thiosemicarbazones. The antimicrobial activity of the compounds was investigated against Candida albicans, Candida dubliniensis, Candida lusitaniae and Candida parapsilosis. In many cases complexation resulted in a substantial increase of the antifungal activity. Complexes (1-4) were revealed to be very active against C. lusitaniae and C. dubliniensis. Structure-activity relationship (SAR) studies were carried out to identify the physico-chemical properties that might be involved in the antifungal action, as well as in the cytotoxic effect of the compounds against HL-60 cells. In both cases, correlations between the bioactivity and physico-chemical properties did not appreciably change when the chloride ligands in [In(L)Cl2(DMSO)] were replaced by water molecules, suggesting [In(L)Cl(H2O)(DMSO)]+ or [In(L)(H2O)2(DMSO)]2+ to be the species that interact with the biological media.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

ABSTRACT The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-β-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

Bismuth(III) complexes with 2-acetylpyridine- and 2-benzoylpyridine-derived hydrazones: Antimicrobial and cytotoxic activities and effects on the clonogenic survival of human solid tumor cells.

Complexes [Bi(2AcPh)Cl2]·0.5H2O (1), [Bi(2AcpClPh)Cl2] (2), [Bi(2AcpNO2Ph)Cl2] (3), [Bi(2AcpOHPh)Cl2]·2H2O (4), [Bi(H2BzPh)Cl3]·2H2O (5), [Bi(H2BzpClPh)Cl3] (6), [Bi(2BzpNO2Ph)Cl2]·2H2O (7) and [Bi(H2BzpOHPh)Cl3]·2H2O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO2Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO2Ph, H2BzpOHPh). Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4). The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts. Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO2Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC50 values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.

Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus.

Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration) in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 2(2) full factorial planning (ANOVA) and on a 2(3) factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC.

The remarkable structural diversity achieved in ent-Kaurane Diterpenes by fungal biotransformations.

The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant species and a myriad of biological activities has been related to these compounds. Studies on structure versus activity have showed that, in most cases, in kaurane diterpenes, activity increases with the increase of functionalization. Since naturally occurring kaurane diterpenes usually have limited functional groups to be used as targets for semi-synthetic modifications, production of more polar derivatives from kaurane diterpenes have been achieved mostly through the use of fungal biotransformations. In this review, selected examples the wonderful chemical diversity produced by fungi in kaurane diterpenes is presented. This diversity includes mainly hydroxylation of nearly all carbon atoms of the kaurane molecule, many of them carried out stereoselectively, as well as ring rearrangements, among other chemical modifications. Sources of starting materials, general biotransformation protocols employed, fungi with most consistent regioselectivity towards kaurane skeleton, as well as biological activities associated with starting materials and products are also described.

Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus

Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration) in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 2² full factorial planning (ANOVA) and on a 2³ factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC.

Structural studies and investigation on the activity of imidazole-derived thiosemicarbazones and hydrazones against crop-related fungi.

New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single crystal X-ray diffraction. The antifungal activities of the compounds were evaluated. None of the compounds exhibited significant activity against Aspergillus flavus and Candida albicans, while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1-yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and 4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases, activity was superior to that of the reference compound nystatin.

Paecilomide, a new acetylcholinesterase inhibitor from Paecilomyces lilacinus.

Fungi are some of the most important organisms in the production of bioactive secondary metabolites. This success is related to the advances in biotechnology and also to the possibility of working with techniques such as the "OSMAC" (one strain-many compounds) to achieve different fungal secondary metabolites profiles upon modifying the culturing conditions. Using this approach, the fungal species Paecilomyces lilacinus was cultivated in potato dextrose broth under 14 different fermentative conditions by adding the bacterium Salmonella typhimurium to the growing medium in order to provide biotic stress. S. typhimurium was added alive or after inactivation by autoclave or microwave irradiation in different stages of fungal growth. Extracts were prepared by liquid-liquid extraction using ethyl acetate, a medium polarity solvent in order to avoid extracting culturing media components. Production of fatty acids of relevance for the pharmaceutical and food industries was enhanced by the modified fermentative conditions and they were identified and quantified. The extracts were evaluated for acetylcholinesterase inhibition and the more active extract (91±2.91% inhibition) was prepared in large scale. From this active P. lilacinus extract, a novel pyridone alkaloid, named Paecilomide, was isolated and its structure was elucidated by modern nuclear magnetic resonance techniques and mass spectrometric analyses. Paecilomide (1) was also evaluated for acetylcholinesterase inhibition, presenting 57.5±5.50% of acetylcholinesterase inhibition.

Modulation of Paecilomyces lilacinus antimicrobial metabolite production by co-culturing with Salmonella typhimurium.

Fungi are important organisms related to the production of antibiotics, many of which are commercially available and used in the clinic to treat infections. Infectious diseases represent a leading cause of death worldwide, being a severe threat to public health, especially with the rise of multi-resistant microorganisms. Therefore, the search for new antibiotic substances is regaining importance. The aim of this study was to evaluate the modulation of the antimicrobial activity of Paecilomyces lilacinus extracts obtained after fungal cultivation in challenging growing conditions, which included the co-cultivation with Salmonella typhimurium, in different levels of inactivation. Two methodologies were used to achieve the antimicrobial response levels of the extracts: disc diffusion and broth microdilution. The extracts showed selective antibacterial activity in response to the presence of bacterial DNA in the medium. The extracts were analysed by HPLC that corroborated that parameter variation influenced the extract chemical profiles.