Synthesis and biological evaluation of novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) as high active anti-HIV agents

A novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) combinatory library was synthesized and evaluated with C8166 cells infected by the HIV-1_IIIB in vitro, using Nevirapine (NVP) and Zidovudine (AZT) as positive control. The anti-HIV screening results revealed that C-6-cyclohexylmethyl substituted pyrimidinones possessed higher selective index than its 6-arylmethyl counterparts. Compounds 1g, 1c, 1e and 1b showed potent anti-HIV activities with EC₅₀ values of 0.012, 0.025, 0.088 and 0.162 nM, respectively.     

Synthesis, structures and ligating properties of 2,6-bis(phosphino)thiophenol derivatives

New t-butyl-aryl thioethers where the aryl group is 2,6-bis(phosphino)phenyl have been synthesized. The syntheses were completed via sequential ortho-lithiations of t-butylphenylsulfide, followed by chlorophosphine (ClPR₂) quenches; symmetric (2,6-bis(diphenylphosphino)phenyl, (4a)) and unsymmetric (2-diisopropylphosphino-6-diphenylphosphino)phenyl, (4b) aryl groups were obtained. Treatment of 4a with Li or Na naphthalenide yielded 2,6-bis(diphenylphosphino)thiophenol 5. Reactions of 4a or 5 with NiCl₂ · 6H₂O yielded nickel bis(phosphinothiophenolate) 6. Compounds 4a,b, 5 and 6 were characterized by ¹H and ³¹P NMR, and by mass-spectrometry. In addition, 4a, 5 and 6 were characterized by single crystal X-ray diffraction methods.     

Synthesis and characterization of platinum(IV) complexes with N,S and S,S heterocyclic ligands

The reactions of [PtMe₃(OAc)(bpy)] (4) with the N,S and S,S containing heterocycles, pyrimidine-2-thione (pymtH), pyridine-2-thione (pytH), thiazoline-2-thione (tztH) and thiophene-2-thiol (tptH), resulted in the formation of the monomeric complexes [PtMe₃(-κS)(bpy)] ( = pymt, 5; pyt, 6; tzt, 7; tpt, 8), where the heterocyclic ligand is coordinated via the exocyclic sulfur atom. In contrast, in the reactions of [PtMe₃(OAc)(Me₂CO)_x] (3, x = 1 or 2) with pymtH, pytH, tztH and tptH dimeric complexes [{PtMe₃(μ-)}₂] (μ- = pymt, 9; pyt, 10; tzt, 11) and the tetrameric complex [{PtMe₃(μ₃-tpt-κS)}₄] (12), respectively, were formed. The complexes were characterized by microanalyses, ¹H and ¹³C NMR spectroscopy and negative ESI-MS (12) measurements. Single-crystal X-ray diffraction analysis of [PtMe₃(pymt-κS)(bpy)] (5) exhibited a conformation where the pymt ligand lies nearly perpendicular to the complex plane above the bpy ligand that was also confirmed by quantum chemical calculations on the DFT level of theory.     

Production of (2S,3S)-2,3-butanediol and (3S)-acetoin from glucose using resting cells of Klebsiella pneumonia and Bacillus subtilis

Production of highly pure (2S,3S)-2,3-butanediol ((2S,3S)-2,3-BD) and (3S)-acetoin ((3S)-AC) in high concentrations is desirable but difficult to achieve. In the present study, glucose was first transformed to a mixture of (2S,3S)-2,3-BD and meso-2,3-BD by resting cells of Klebsiella pneumoniae CICC 10011, followed by biocatalytic resolution of the mixture by resting cells of Bacillus subtilis 168. meso-2,3-BD was transformed to (3S)-AC, leaving (2S,3S)-2,3-BD in the reaction medium. Using this approach, 12.5 g l(-1) (2S,3S)-2,3-BD and 56.7 g l(-1) (3S)-AC were produced. Stereoisomeric purity of (2S,3S)-2,3-BD and enantiomeric excess of (3S)-AC was 96.9 and 96.2%, respectively.     

Selective liberation of NO from S-nitrosocysteine with potassium thiocyanate, as monitored by an amperometric sensor

S-Nitrosocysteine (CysNO) releases either NO (in the presence of divalent cations) or NO+ (in the presence of chelating agents). NO+ is then transferred to peptides or protein SH groups to form high-mass nitrosothiols. The aim of this work was the development of a specific reaction between thiocyanate (SCN-) and CysNO. This reaction selectively liberates NO from CysNO in the presence of high-mass nitrosothiols. Free NO is measured with an amperometric sensor. We examine with this system the transnitrosylation reaction between CysNO and BSA at low molecular ratios and could assay nitrites, SNO-BSA, and CysNO in the incubation mixture without any preliminary purification steps.     

The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver

Retinyl esters are the major chemical forms of vitamin A stored in the liver, and can be delivered to peripheral tissues for conversion into biologically active forms. The function and regulation of the hepatic genes that are potentially involved in catalyzing the hydrolysis of retinyl esters remain unclear. Here we show that two lipid hydrolytic genes, pancreatic-related protein 2 (mPlrp2) and procolipase (mClps), expressed specifically in the mouse pancreas, are associated with the ratio of S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). Light illumination deficiency or administration of 5'-AMP elevated the ratio of AdoMet to AdoHcy and induced the expression in the liver of mPlrp2 and mClps, which was blocked by all-trans retinoic acid. Mice fed a vitamin A-free diet exhibited increased activation of hepatic mPlrp2 and mClps expression, which was associated with increased methylation of histone H3K4 residues located near the mPlrp2 and mClps promoters. Inhibition of hepatic mPlrp2 and mClps expression by a methylase inhibitor, methylthioadenosine, markedly decreased plasma retinol levels in these mice. The activated hepatic stellate cell (HSC)-T6 cell line specifically expressed mClps and mPlrp2. Inhibition of mClps gene expressions by short hairpin RNA (shRNA) decreased hydrolysis of retinyl esters in the HSC-T6 cell line. These data suggest that the conditional expression of mPlrp2 and mClps is involved in the hydrolysis of retinyl esters in the mouse liver.     

Tertiary structure of thiopurine methyltransferase from Pseudomonas syringae, a bacterial orthologue of a polymorphic, drug-metabolizing enzyme

In humans, the enzyme thiopurine methyltransferase (TPMT) metabolizes 6-thiopurine (6-TP) medications, including 6-thioguanine, 6-mercaptopurine and azathioprine, commonly used for immune suppression and for the treatment of hematopoietic malignancies. S-Methylation by TPMT prevents the intracellular conversion of these drugs into active 6-thioguanine nucleotides (6-TGNs). Genetic polymorphisms in the TPMT protein sequence have been associated with decreased tissue enzymatic activities and an increased risk of life-threatening myelo-suppression from standard doses of 6-TP medications. Biochemical studies have demonstrated that TPMT deficiency is primarily associated with increased degradation of the polymorphic proteins through an ubiquitylation and proteasomal-dependent pathway. We have now determined the tertiary structure of the bacterial orthologue of TPMT from Pseudomonas syringae using NMR spectroscopy. Bacterial TPMT similarly catalyzes the S-adenosylmethionine (SAM)-dependent transmethylation of 6-TPs and shares 45% similarity (33% identity) with the human enzyme. Initial studies revealed an unstructured N terminus, which was removed for structural studies and subsequently determined to be required for enzymatic activity. Despite lacking sequence similarity to any protein of known three-dimensional structure, the tertiary structure of bacterial TPMT reveals a classical SAM-dependent methyltransferase topology, consisting of a seven-stranded beta-sheet flanked by alpha-helices on both sides. However, some deviations from the consensus topology, along with multiple insertions of structural elements, are evident. A review of the many experimentally determined tertiary structures of SAM-dependent methyltransferases demonstrates that such structural deviations from the consensus topology are common and often functionally important.     

Preparation, properties and crystal structure of two isomers of R,R,S,S- and R,S,R,S-[chloro(1,3,10,12,16,19-hexaazatetracyclo[17,3,1,1,0]tetracosane)copper(II)]

Two isomers (R,S,R,S- and R,R,S,S-) of five coordinate complex [Cu(L)Cl]⁺ have been separated and characterised. These two isomers have significantly different spectrochemical and electrochemical properties. Absorption maximum of R,S,R,S-[Cu(L)Cl]⁺ shifts to longer wavelength and its reduction potential shifts to more positive direction comparing those of R,R,S,S-[Cu(L)Cl]⁺. R,S,R,S-[Cu(L)Cl]⁺ is significantly distorted to trigonal-bipyramidal structure, whereas R,R,S,S-[Cu(L)Cl]⁺ retains almost square-planar geometry. The average bond distance of Cu-N in basal plane of R,S,R,S-[Cu(L)Cl]⁺ is longer by 0.024 Å than that of R,R,S,S-[Cu(L)Cl]⁺, whereas the bond distance of Cu-Cl in former is shorter by 0.200 Å than that in latter. The isolated square-planar complexes of R,R,S,S- and R,S,R,S-[Cu(L)](ClO₄)₂ are converted to the R,R,S,S- and R,S,R,S-[Cu(L)Cl]⁺ by the addition of Cl⁻ in nitromethane solution with the rate constants, k=1.70 (±0.02) and 8.31 (±0.07) M⁻¹ s⁻¹, respectively.     

Force field parameters for S-nitrosocysteine and molecular dynamics simulations of S-nitrosated thioredoxin

Estimation of structural perturbation induced by S-nitrosation is important to understand the mode of cellular signal transduction mediated by nitric oxide. Crystal structures of S-nitrosated proteins have been solved only for a few cases, however, so that molecular dynamics simulation may provide an alternative tool for probing structural perturbation. In this study AMBER-99 force field parameters for S-nitrosocysteine were developed and applied to molecular dynamics simulations of S-nitrosated thioredoxin. Geometry optimization at the level of HF/6-31G∗ was followed by a restrained electrostatic potential charge-fitting to obtain the atomic charges of S-nitrosocysteine. Force constants for bonds and angles were obtained from generalized AMBER force field. Torsional force constants for CC-SN and CS-NO were determined by fitting the torsional profiles obtained from geometry optimization with those from molecular mechanical energy minimization. Finally molecular dynamics simulations were performed with theses parameters on oxidized and reduced thioredoxin with and without S-nitrosocysteine. In all cases the root-mean-square deviations of α-carbons yielded well-behaved trajectories. The CC-SH dihedral angle which fluctuated severely during the simulation became quiet upon S-nitrosation. In conclusion the force field parameters developed in this study for S-nitrosocysteine appear to be suitable for molecular dynamics simulations of S-nitrosated proteins.     

Hydroperoxy-arachidonic acid mediated n-hexanal and (Z)-3- and (E)-2-nonenal formation in Laminaria angustata

In higher plants, C6 and C9 aldehydes are formed from C18 fatty acids, such as linoleic or linolenic acid, through formation of 13- and 9-hydroperoxides, followed by their stereospecific cleavage by fatty acid hydroperoxide lyases (HPL). Some marine algae can also form C6 and C9 aldehydes, but their precise biosynthetic pathway has not been elucidated fully. In this study, we show that Laminaria angustata, a brown alga, formed C6 and C9 aldehydes enzymatically. The alga forms C9 aldehydes exclusively from the C20 fatty acid, arachidonic acid, while C6 aldehydes are derived either from C18 or from C20 fatty acid. The intermediates in the biosynthetic pathway were trapped by using a glutathione/glutathione peroxidase system, and subjected to structural analyses. Formation of (S)-12-, and (S)-15-hydroperoxy arachidonic acids [12(S)HPETE and 15(S)HPETE] from arachidonic acid was confirmed by chiral HPLC analyses. These account respectively for C9 aldehyde and C6 aldehyde formation, respectively. The HPL that catalyzes formation of C9 aldehydes from 12(S)HPETE seems highly specific for hydroperoxides of C20 fatty acids.     

Synthetic, EPR spectroscopic, magnetic and X-ray crystallographic structural studies on copper(II) complexes of the tridentate N2S donor ligand formed from 6-methyl-2-formylpyridine and S-methyldithiocarbazate (Hmpsme)

New copper(II) complexes of general empirical formula, Cu(mpsme)X · xCH₃COCH₃ (mpsme = anionic form of the 6-methyl-2-formylpyridine Schiff base of S-methyldithiocarbazate; X = Cl, N₃, NCS, NO₃; x = 0, 0.5) have been synthesized and characterized by IR, electronic, EPR and susceptibility measurements. Room temperature μ_eff values for the complexes are in the range 1.75-2.1 μ_B typical of uncoupled or weakly coupled Cu(II) centres. The EPR spectra of the [Cu(mpsme)X] (X = Cl, N₃, NO₃, NCS) complexes reveal a tetragonally distorted coordination sphere around the mononuclear Cu(II) centre. We have exploited second derivative EPR spectra in conjunction with Fourier filtering (sine bell and Hamming functions) to extract all of the nitrogen hyperfine coupling matrices. While the X-ray crystallography of [Cu(mpsme)NCS] reveals a linear polymer in which the thiocyanate anion bridges the two copper(II) ions, the EPR spectra in solution are typical of a magnetically isolated monomeric Cu(II) centres indicating dissociation of the polymeric chain in solution. The structures of the free ligand, Hmpsme and the {[Cu(mpsme)NO₃] · 0.5CH₃COCH₃}₂ and [Cu(mpsme)NCS]_n complexes have been determined by X-ray diffraction. The {[Cu(mpsme)NO₃] 0.5CH₃COCH₃}₂ complex is a centrosymmetric dimer in which each copper atom adopts a five-coordinate distorted square-pyramidal geometry with an N₂OS₂ coordination environment, the Schiff base coordinating as a uninegatively charged tridentate ligand chelating through the pyridine and azomethine nitrogen atoms and the thiolate, an oxygen atom of a unidentate nitrato ligand and a bridging sulfur atom from the second ligand completing the coordination sphere. The [Cu(mpsme)(NCS)]_n complex has a novel staircase-like one dimensional polymeric structure in which the NCS⁻ ligands bridge two adjacent copper(II) ions asymmetrically in an end-to-end fashion providing its nitrogen atom to one copper and the sulfur atom to the other.     

O(2)-dependent stimulation of the pentose phosphate pathway by S-nitrosocysteine in human erythrocytes

In the present study we analysed the effects of S-nitrosocysteine (CysNO) on adult human red blood cell metabolism and observed that metabolic response depended on the degree of cell oxygenation. In particular, glucose metabolised through the pentose phosphate pathway (PPP) was higher in treated erythrocytes than in untreated cells only at high O(2) pressure. Since, following the treatment of intact cells with CysNO, glucose-6-phosphate dehydrogenase (G6PD) and phosphofructokinase (PFK) activities did not evidence any significant alteration, the possibility that the stimulation of PPP was triggered by a CysNO mediated modification of these enzymes was excluded. Intracellular S-nitrosoglutathione (GSNO), detected only in treated red blood cells, may be linked solely to the exposition to the NO donor. A possible rationalisation of the different metabolic behaviour shown by erythrocytes as a function of their oxygenation state is proposed. It takes into account the different route of catabolic degradation observed in vitro for GSNO under aerobic and anaerobic condition.     

High-level expression and characterization of two chitinases, ChiCH and ChiCW, of Bacillus cereus 28-9 in Escherichia coli

Many chitinase genes have been cloned and sequenced from prokaryotes and eukaryotes but overexpression of chitinases in Escherichia coli cells was less reported. ChiCH and ChiCW of Bacillus cereus 28-9 belong to two distinct groups based on their amino acid sequences of catalytic domains, and in addition, domain structures of two enzymes are different. In this study, we established an ideal method for high-level expression of chitinases in E. coli as glutathione-S-transferase fusion proteins using pGEX-6P-1 vector. Both ChiCH and ChiCW were successfully highly expressed in E. coli cells as soluble GST-chitinase fusion proteins, and recombinant native ChiCH and ChiCW could be purified after cleavage with PreScission protease to remove GST tag. Purified chitinases were used for biochemical characterization of kinetics, hydrolysis products, and binding activities. The results indicate that ChiCW is an endo-chitinase and effectively hydrolyzes chitin and chito-multimers to chito-oligomers and the end product chitobiose, and ChiCH is an exo-chitinase and degrades chito-oligomers to produce chitobiose. Furthermore, due to higher affinity of ChiCW toward colloidal chitin than Avicel, C-terminal domain of ChiCW should be classified as a chitin-binding domain not a cellulose-binding domain although that was revealed as a cellulose-binding domain by conserved domain analysis. Therefore, the method of high-level expression of chitinases is helpful to studies and applications of chitinases.     

Structural and functional characterization of a plant S-nitrosoglutathione reductase from Solanum lycopersicum

S-nitrosoglutathione reductase (GSNOR), also known as S-(hydroxymethyl)glutathione (HMGSH) dehydrogenase, belongs to the large alcohol dehydrogenase superfamily, namely to the class III ADHs. GSNOR catalyses the oxidation of HMGSH to S-formylglutathione using a catalytic zinc and NAD⁺ as a coenzyme. The enzyme also catalyses the NADH-dependent reduction of S-nitrosoglutathione (GSNO). In plants, GSNO has been suggested to serve as a nitric oxide (NO) reservoir locally or possibly as NO donor in distant cells and tissues. NO and NO-related molecules such as S-nitrosothiols (S-NOs) play a central role in the regulation of normal plant physiological processes and host defence. The enzyme thus participates in the cellular homeostasis of S-NOs and in the metabolism of reactive nitrogen species. Although GSNOR has recently been characterized from several organisms, this study represents the first detailed biochemical and structural characterization of a plant GSNOR, that from tomato (Solanum lycopersicum). SlGSNOR gene expression is higher in roots and stems compared to leaves of young plants. It is highly expressed in the pistil and stamens and in fruits during ripening. The enzyme is a dimer and preferentially catalyses reduction of GSNO while glutathione and S-methylglutathione behave as non-competitive inhibitors. Using NAD⁺, the enzyme oxidizes HMGSH and other alcohols such as cinnamylalcohol, geraniol and ω-hydroxyfatty acids. The crystal structures of the apoenzyme, of the enzyme in complex with NAD⁺ and in complex with NADH, solved up to 1.9 Å resolution, represent the first structures of a plant GSNOR. They confirm that the binding of the coenzyme is associated with the active site zinc movement and changes in its coordination. In comparison to the well characterized human GSNOR, plant GSNORs exhibit a difference in the composition of the anion-binding pocket, which negatively influences the affinity for the carboxyl group of ω-hydroxyfatty acids.     

S-adenosylmethionine radical enzymes

The role of S-adenosylmethionine (SAM) as a precursor to organic radicals, generated by one-electron reduction of SAM and subsequent fission to form 5'-deoxyadenosyl radical and methionine, has been known for some time. Only recently, however, has it become apparent how widespread such enzymes are, and what a wide range of chemical reactions they catalyze. In the last few years several new SAM radical enzymes have been identified. Spectroscopic and kinetic investigations have begun to uncover the mechanism by which an iron sulfur cluster unique to these enzymes reduces SAM to generate adenosyl radical. Most recently, the first X-ray structures of SAM radical enzymes, coproporphyrinogen-III oxidase, and biotin synthase have been solved, providing a structural framework within which to interpret mechanistic studies.     

Using S-adenosyl-l-homocysteine capture compounds to characterize S-adenosyl-l-methionine and S-adenosyl-l-homocysteine binding proteins

S-Adenosyl-l-methionine (SAM) is recognized as an important cofactor in a variety of biochemical reactions. As more proteins and pathways that require SAM are discovered, it is important to establish a method to quickly identify and characterize SAM binding proteins. The affinity of S-adenosyl-l-homocysteine (SAH) for SAM binding proteins was used to design two SAH-derived capture compounds (CCs). We demonstrate interactions of the proteins COMT and SAHH with SAH–CC with biotin used in conjunction with streptavidin–horseradish peroxidase. After demonstrating SAH-dependent photo-crosslinking of the CC to these proteins, we used a CC labeled with a fluorescein tag to measure binding affinity via fluorescence anisotropy. We then used this approach to show and characterize binding of SAM to the PR domain of PRDM2, a lysine methyltransferase with putative tumor suppressor activity. We calculated the K_d values for COMT, SAHH, and PRDM2 (24.1 ± 2.2 μM, 6.0 ± 2.9 μM, and 10.06 ± 2.87 μM, respectively) and found them to be close to previously established K_d values of other SAM binding proteins. Here, we present new methods to discover and characterize SAM and SAH binding proteins using fluorescent CCs.     

Cyanogenic glycosides and menisdaurin from Guazuma ulmifolia, Ostrya virgininana, Tiquilia plicata and Tiquilia canescens

The major cyanogenic glycoside of Guazuma ulmifolia (Sterculiaceae) is (2R)-taxiphyllin (>90%), which co-occurs with (2S)-dhurrin. Few individuals of this species, but occasional other members of the family, have been reported to be cyanogenic. To date, cyanogenic compounds have not been characterized from the Sterculiaceae. The cyanogenic glycosides of Ostrya virginiana (Betulaceae) are (2S)-dhurrin and (2R)-taxiphyllin in an approximate 2:1 ratio. This marks the first report of the identification of cyanogenic compounds from the Betulaceae. Based on NMR spectroscopic and TLC data, the major cyanogenic glucoside of Tiquilia plicata is dhurrin, whereas the major cyanide-releasing compound of Tiquilia canescens is the nitrile glucoside, menisdaurin. NMR and TLC data indicate that both compounds are present in each of these species. The spectrum was examined by CI-MS, ¹H and ¹³C NMR, COSY, 1D selective TOCSY, NOESY, and ¹J/^2,3J HETCOR experiments; all carbons and protons are assigned. The probable absolute configuration of (2R)-dhurrin is established by an X-ray crystal structure. The ¹H NMR spectrum of menisdaurin is more complex than might be anticipated, containing a planar conjugated system in which most elements are coupled to several other atoms in the molecule. The coupling of one vinyl proton to the protons on the opposite side of the ring involves a ⁶J- and a ^5/7J-coupling pathway. A biogenetic pathway for the origin of nitrile glucosides is proposed.     

A simple bacterial transformation method using magnesium- and calcium-aminoclays

An efficient and user-friendly bacterial transformation method by simple spreading cells with aminoclays was demonstrated. Compared to the reported transformation approaches using DNA adsorption or wrapping onto (in)organic fibers, the spontaneously generated clay-coated DNA suprastructures by mixing DNA with aminoclay resulted in transformants in both Gram-negative (Escherichia coli) and Gram-positive cells (Streptococcus mutans). Notably, the wild type S. mutans showed comparable transformation efficiency to that of the E. coli host for recombinant DNA cloning. This is a potentially promising result because other trials such as heat-shock, electroporation, and treatment with sepiolite for introducing DNA into the wild type S. mutans failed. Under defined conditions, the transformation efficiency of E. coli XL1-Blue and S. mutans exhibited ~ 2 × 10⁵ and ~ 6 × 10³ CFU/μg of plasmid DNA using magnesium-aminoclay. In contrast, transformation efficiency was higher in S. mutans than that in E. coli XL1-Blue for calcium-aminoclay. It was also confirmed that each plasmid transformed into E. coli and S. mutans was stably maintained and that they expressed the inserted gene encoding the green fluorescent protein during prolonged growth of up to 80 generations.     

Dehydrogenases,Acid and Alkaline Phosphatases,and Esterases for Chemotaxonomy of Selected Meloidogyne,Ditylenchus, Heterodera and Aphelenchus spp.

Various taxonomically useful profiles of four dehydrogenases (lactate, malate, glucose-6-phosphate, and a-glycerophosphate) and three hydrolases (acid and alkaline phosphatase and esterase) were detected in whole nematode homogenates of Meloidogyne javanica, M. hapla, M. incognita, M. arenaria, Ditylenchus dipsaci, D. triformis, Heterodera glycines, and Aphelenchus avenae. The enzyme profiles were stable in populations cultured on several different hosts. A tentative enzymically-determined phylogeny of Meloidogyne is given.     

Stereospecific ligands and their complexes. V. Synthesis, characterization and antimicrobial activity of palladium(II) complexes with some alkyl esters of (S,S)-ethylenediamine-N,N′-di-2-propanoic acid

Three new ligands and their palladium(II) complexes of general formula [PdCl₂(R₂-S,S-eddp)] (R = n-propyl, n-butyl and n-pentyl) have been synthesized and characterized by microanalysis, infrared and ¹H and ¹³C NMR spectroscopy. Antimicrobial activity of these ligands and complexes was tested by microdilution method and both minimal inhibitory and microbicidal concentration were determined. These tested complexes demonstrated the significant antifungal activity against pathogenic fungi Aspergillus flavus and Aspergillus fumigatus. On the other hand, these complexes demonstrated moderate antibacterial activity.