Mycosynthesis of silver nanoparticles using marine fungi and their antimicrobial activity against pathogenic microorganisms.

OBJECTIVES: At the present time, there is a persistent need to get rid of environmental contaminants by eco-friendly, sustainable, and economical technologies. Uncontrolled disposal practices of domestic and industrial solid and liquid wastes led to water pollution which has negative impacts on public health, environment, and socio-economic development. Several water-borne diseases are spreading man to man by microorganisms such as pathogenic bacteria. For the protection of water bodies, all wastewater from various sources should be managed and remediated properly. Myco-remediation is a form of bioremediation in which fungi are used to get rid of contaminants. Fungi are attractive agents for the biosynthesis of nanoparticles especially silver nanoparticles (AgNPs) which are considered one of the most widely utilized nanoparticles because of their unique characteristics such as antibacterial, antiviral, antifungal, and anti-inflammatory properties. METHODS: This study uses silver nitrate and supernatants of four marine fungi; Penicillium simplicissimum, Aspergillus terreus, Aspergillus japonicus, and Aspergillus oryzae for extracellular biosynthesis of silver nanoparticles and to evaluate its activity against different pathogenic microorganisms. These nanoparticles may subsequently be applied for the treatment or nano-bioremediation of microbial contaminants in water bodies and improve water quality. RESULTS: Silver nanoparticles were synthesized and the results revealed that spherical and well-dispersed nanoparticles of different sizes were formed with sizes ranging between 3.8 and 23 nm. Characterization results approved the existence of stable nanocrystalline elemental silver. Antibacterial activity results revealed that AgNPs can be used as a powerful antimicrobial agent for several pathogenic bacteria, yeast, and fungi. Among the biosynthesized NPs mediated by the four marine fungi, AgNPs mediated by A. japonicus (5 mM) had the highest antibacterial activity, while AgNPs mediated by Penicillium simplicissmum (8 mM) had the highest antifungal activity. CONCLUSION: Marine fungi can biosynthesize stable AgNPs that exhibit potent antimicrobial activity against a variety of pathogens.

A Study on the Bio-responses of a Freshwater Snail (Biomphalaria alexandrina) to Fungal-derived Compounds.

BACKGROUND: Biomphalaria alexandrina snails, as transitional hosts of schistosomiasis, plays an essential part in the spread of the illness. Control of these snails by the substance molluscicides antagonistically influences the oceanic climate, causing poisonous and cancer-causing consequences for non-target life forms. OBJECTIVE: Looking for new naturally safe substances that can treat schistosomiasis disease with minimal side effects on the environment and plants, fish wealth and do not affect vital human functions. METHODS: Fifty fungal species were used to evaluate their activity against Biomphalaria alexandrina. Study the effect of the fungal extract on vital functions of Biomphalaria alexandrina and fish wealth. Purification of active substances and identification of their chemical structures. RESULTS: Cladosporium nigrellum and Penicillium aurantiogresium metabolites were effective against B. alexandrina snails, and the effects of promising fungal extracts sublethal concentrations (IC10 & IC25) on the levels of steroid sex hormones, liver enzymes, total protein, lipids, albumin and glucose were determined. Chemical analyses of this filtrate separated a compound effective against snails; it was identified. Protein electrophoresis showed that fungal filtrate affects the protein pattern of snails' haemolymph. Little or no mortality of Daphnia pulex individuals was observed after their exposure to sublethal concentrations of each treatment. CONCLUSION: Certain compounds from fungal cultures could be safely used for biological control of Biomphalaria alexandrina snails.

Rhizopus oryzae AM16; a new hyperactive L-asparaginase producer: Semi solid-state production and anticancer activity of the partially purified protein.

The demand for L-asparaginase is predicted to increase several fold in the future due to its potential clinical applications in the treatment of lymphoid system malignancies and leukemia. Thus identifying suitable sources of production should be considered high priority. Fungi are valuable organisms as they are able to convert what would be considered 'useless' materials into materials that have potential value. The present study provides a proof of concept of production of a new hyperactive L-asparaginase producer (Rhizopus oryzae AM16), which was successfully isolated and sequentially optimized using a semi solid-state fermentation method with a simple and cheap medium produced from wheat bran (WB). The fungus was able to produce an appreciable amount of the enzyme (2,875.9 U) after 8 days of incubation under 85.7% moisture, in the presence of magnesium nitrate (5.0 mg N/mg nitrogen per gram of dry WB) at pH 5.8. Testing the anticancer activity confirmed the ability of the resultant enzyme to inhibit the growth of various types of cancer cells (HepG2, MCF-7, HCT and A549). The IC50 values of the dialyzed enzyme were lower than that of the crude product. Thus, this newly identified and purified L-asparaginase may be a promising anticancer drug.

Monascin and monascinol, azaphilonoid pigments from Mortierella polycephala AM1: in silico and in vitro targeting of the angiogenic VEGFR2 kinase.

The fungus, Mortierella polycephala is one of the most productive sources of anticancer bioactive compounds namely those of pigment nature. During our investigation of the produced bioactive metabolites by the terrestrial M. polycephala AM1 isolated from Egyptian poultry feather waste, two main azaphilonoid pigments, monascin (1) and monascinol (2) were obtained as major products; their structures were identified by 1D (1H&13C) and 2D (1H-1H COSY, HMBC) NMR and HRESI-MS spectroscopic data. Biologically, cytotoxic activities of these compounds were broadly studied compared with the fungal extract. To predict the biological target for the presumed antitumor activity, an in silico study was run toward three proteins, topoisomerase IIα, topoisomerase IIß, and VEGFR2 kinase. Monascinol (2) was expected to be moderately active against VEGFR2 kinase without any anticipated inhibition toward topo II isoforms. The in vitro study confirmed the docked investigation consistently and introduced monascinol (2) rather than its counterpart (1) as a potent inhibitor to the tested VEGFR2 kinase. Taxonomically, the fungus was identified using morphological and genetic assessments.

Synthesis and in vitro anticancer evaluation of some fused indazoles, quinazolines and quinolines as potential EGFR inhibitors.

derivatives of benzo[g]indazole 5a, b, benzo[h]quinazoline 7, 12a-c, 13a-c and 15a-c and benzo[h]quinoline 17a-c and 19a-c were synthesized from 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1). Anticancer activity of all the synthesized compounds was evaluated against four cancerous cell lines; HepG2, MCF-7, HCT116 and Caco-2. MCF-7 cells emerged as the most sensitive cell line against the target compounds. All the examined compounds, except 5a and 5b, displayed potent to moderate anticancer activity against MCF-7 cells with an IC50 values ranging from 7.21 to 21.55 µM. In particular, compounds 15c and 19b emerged as the most potent derivatives against EGFR-expressing MCF-7 cells with IC50 values = 7.70 ±â€¯0.39 and 7.21 ±â€¯0.43 µM, respectively. Additionally, both compounds did not display any significant cytotoxicity towards normal BHK-21 fibroblast cells (IC50 value > 200 µM), thereby providing a good safety profile as anticancer agents. Furthermore, compounds 15c and 19b displayed potent inhibitory activity towards EGFR in the sub-micromolar range (IC50 = 0.13 ±â€¯0.01 and 0.14 ±â€¯0.01 µM, respectively), compared to that of Erlotinib (IC50 = 0.11 ±â€¯0.01 µM). Docking studies for 15c and 19b into EGFR active site was carried out to explore their potential binding modes. Therefore, compounds 15c and 19b can be considered as interesting candidates for further development of more potent anticancer agents.

Impact of nanoencapsulated natural bioactive phenolic metabolites on chitosan nanoparticles as aflatoxins inhibitor.

Aflatoxins are part of fungal secondary metabolites which become serious health, environmental, and economic problems and can cause corruption of many crops and agricultural grains that used as food and feed for human and animal. Aflatoxins mainly produce by Aspergillus spp. especially Aspergillus flavus and Aspergillus parasiticus. The present work aimed to study the effect of nanoencapsulation of chitosan (CS) nanoparticles with two phenolic compounds 1-(2-ethyl,6-heptyl)phenol (EHP) extracted from Cuminum cyminum and 5-ethyl-2-(methoxymethyl)phenol (EMMP) extracted from black pepper on growth and aflatoxins production of A. flavus and A. parasiticus. A. flavus growth was completely inhibited by 0.6 mg/ml of EHP and EMMP as well as A. parasiticus which showed the same minimal inhibition concentration with the first compound and 0.8 mg/ml with the second one. CS nanoparticles inhibited the growth of the tested organisms more than CS especially with A. parasiticus and this potency became much better when nanoencapsulated with the two extracted phenolic compounds. In inhibition of aflatoxins production, EHP reduced the production of aflatoxin B1 and B2 of A. flavus by 68.6% and 69.7%, respectively. In the same manner EMMP reduce the production of the two toxins by 87.3% and 82.6%, respectively. The reduction effect of CS nanoparticles is much more than that of CS as it record in most cases about twofold increase. Nanoencapsulation of CS nanoparticles by the extracted phenolic compounds is much more effective with complete inhibition of aflatoxin B1 of both fungi and aflatoxin G1 of A. parasiticus.

Biological and hematological responses of Biomphalaria alexandrina to mycobiosynthsis silver nanoparticles.

Silver nanoparticles (AgPNs) extracts were prepared from seven Seven fungal isolates were evaluated through measuring their toxicity against Biomphalaria alexandrina snails. The effects of the two promising Paecilomyces variotii and Aspergillus niger AgNPs sublethal concentrations (LC10 & LC25) on the levels of steroid sex hormones, liver enzymes, total protein, lipids, albumhin, glucose, total and differential count of hemocytes and morphology of hemocytes, oocytes and sperms were studied in this work. The short period of snails' exposure (24h) to the two fungal AgNPs resulted in significant decrease in the levels of progesterone in B. alexandrina. The level of testosterone hormone showed significant increase in snails exposed to P. variotii AgNPs while no significant change was recorded at the exposure to A. niger AgNPs. Also, estradiol hormone concentration increased significantly in this investigation with the increase of the concentration of the two tested compounds. In addition, significant elevation in ALT, AST and Alkaline phosphatase was recorded. The total number of the hematocytes increased significantly by 17.4-47.8%. Snails' granulocytes were reduced by 19.1-43.8%, while hyalinocytes increased by 63.6-354.5%. The exposure of B. alexandrina to LC25 of both P. variotii and A. niger AgNPs showed apoptotic hemolymph cells, fragmented, vacuolated and degenerated cytoplasm, shrunken nucleus and phagocytosis in the light microscopy photographs of the hemocytes. Besides, the photographs showed also, abnormal nuclear division, degeneration and large fat vacuoles in the cytoplasm and swallowed atretic oocytes. Also, the photographs showed dead sperm head separated from its tail, other sperms showed abnormal swallowed head with severely nodded tail, dead sperms with wrinkled tails, hyperplasia and necrotic sperm heads led to overlapping of tails. In conclusion, applying the biosynthesized compounds which led to destruction of blood cells (the immune system), ova and sperms (the reproductive system) of snails is an important effective step to control schistosomiasis.

Stereoselective synthesis and antimicrobial activity of benzofuran-based (1E)-1-(piperidin-1-yl)-N2-arylamidrazones.

The reaction of 2-oxo-N-arylpropanehydrazonoyl chlorides 3a-e with 3-methyl-2-benzofurancarboxylic acid hydrazide (7) furnished N-(aryl)propanehydrazonoyl chlorides 8a-e. X-Ray of 8c revealed the (1Z,2E) configuration of structure 8. Nucleophilic substitution reaction of 8a or 8d with piperidine resulted in the formation of 1-(piperidin-1-yl)-N(2)-arylamidrazones 9a, b. The X-ray diffraction of 9b showed its (1E,2E) configuration and it confirmed the stereoselectivity of the latter reaction. (1E,2Z,3E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(3-methylbenzofuran-2-oyl)hydrazono]-4-arylbut-3-enes 11 were synthesized in stereoselective reaction from 8 or alternatively from 9. X-ray analysis of 11b showed a conversion of configuration respect to 8d or 9b. X-Ray analysis of 9b and 11b revealed the role of hydrogen interactions in the stereochemistry of their solid state structure. The in vitro antimicrobial activity of the newly synthesized compounds demonstrated an excellent growth inhibition of compounds 9 and 11 against clinically isolated strains of human fungal pathogens and exhibited a significant potency against gram-positive bacteria. Griseofulvin and Amoxicilline were used as references for antifungal and antibacterial screening. The effect of most potent antifungal compound 9b on morphological features of Aspergillus fumigatus and Candida albicans using image analyzer was studied. Furthermore, the effect of 9b on the ultra-structures of the latter fungi was occurred by transmission electron microscope.

Convenient synthesis and antimicrobial evaluation of some novel 2-substituted-3-methylbenzofuran derivatives.

The reaction of 3-methylbenzofuran-2-carbohydrazide (1) with l-phenyl-2-bromoethanone (2a) or 2-chloro-1-(4-chlorophenyl)ethanone (2b) afforded (Z)-1,2-di[(3-methylbenzofuran-2-carbohydrazido]-1-arylethenes 5a and 5b, respectively. Single crystal X-ray analyses of compound 5a proved that the reaction proceeds in 2:1 molar ratio and ruled out the other possible structures 1,3,4-oxadiazine derivative 6 or E-isomer 7. Furthermore, both of 3-(3-methylbenzofuran-2-yl)-3-oxopropanenitrile (9) and 3-methyl-2-benzofuranoyl chloride (15) were used as starting materials for the synthesis of several compounds, such as pyrazoles 10 and 14, oxime 11, hydrazones 12a, b and 3,1-bezoxazine 19. The newly synthesized compounds were tested for their antimicrobial activity against five fungal species and four bacterial species also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Some of these compounds exhibited a significant antimicrobial activity.