Synthesis of Hemiprotonic Phenanthroline-Phenanthroline+ Compounds with both Antitumor and Antimicrobial Activity.

Currently, cancer patients with microbial infection are a severe challenge in clinical treatment. To address the problem, we synthesized hemiprotonic compounds based on the unique structure of hemiprotonic nucleotide base pairs in a DNA i-motif. These compounds were produced from phenanthroline (ph) dimerization with phenanthroline as a proton receptor and ammonium as a donor. The biological activity shows that the compounds have a selective antitumor effect through inducing cell apoptosis. The molecular mechanism could be related to specific inhibition of transcription factor PLAGL2 of tumor cells, assessed by transcriptomic analysis. Moreover, results show that the hemiprotonic ph-ph+ has broad-spectrum antibacterial and antifungal activities, and drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus, are sensitive to the compound. In animal models of liver cancer with fungal infection, the ph-ph+ retards proliferation of hepatoma cells in tumor-bearing mice and remedies pneumonia and encephalitis caused by Cryptococcus neoformans. The study provides a novel therapeutic candidate for cancer patients accompanied by infection.

Synthesis and in vitro antifungal activity of new Michael-type amino derivatives of xanthatin, a natural sesquiterpene lactone from Xanthium strumarium L.

Structural optimization using plant secondary metabolites as templates is one of the important approach to discover pesticide molecules with novel skeletons. Xanthatin, a natural sesquiterpene lactone isolated from the Xanthium plants (Family: Compositae), exhibits important biological properties. In this work, a series of Michael-type amino derivatives were prepared from xanthatin and their structures were characterized by 1H NMR, 13C NMR and HR-MS, and their antifungal activities against several phytopathogenic fungi were evaluated according to the spore germination method and mycelium growth rate method in vitro. The results illustrated that compounds 2g (IC50 = 78.91 µg/mL) and 2o (IC50 = 64.51 µg/mL) exhibited more promising inhibition activity against spores of F. solani than precursor xanthatin, compounds 2g, 2l, and 2r exhibited remarkable antifungal effect on C. mandshurica with the average inhibition rates (AIRs) >90%, whereas the AIR of xanthatin was only 59.34%. Meanwhile, the preliminary structure-activity relationships suggested that the amino containing 2-methoxyethyl or 4-chlorophenylmethyl group appended in the C-13 position of xanthatin could yield potential compounds against fungal spores, and the exocyclic double bond of xanthatin is essential to maintain its mycelial growth inhibitory activity. Therefore, the aforementioned findings indicate that partial xanthatin amino-derivatives could be considered for further exploration as the potential lead structures toward development of the new environmentally friendly fungicidal candidates for sustainable crop protection.

Design, synthesis, biological screening and molecular docking studies of novel multifunctional 1,4-di (aryl/heteroaryl) substituted piperazine derivatives as potential antitubercular and antimicrobial agents.

In this paper, two series of novel multifunctional 1, 4-di (aryl/heteroaryl) substituted piperazine derivatives (6a-d & 7a-d) were synthesized, characterized, and evaluated for their antitubercular, antibacterial, and antifungal activities. A step-wise reduction, bromination and substitution reactions on various aldehydes resulted in alcohols (2a-d), bromides (3a-d), and titled novel compounds (6a-d & 7a-d) in moderate to good yields (48-85%). The novel compounds were evaluated for their antitubercular and antimicrobial activities. Compound 7a exhibited promising antitubercular activity (MIC: 0.65 µg/mL) almost equal to the Rifampicin, while the rest of the compounds were moderately active against MTB H37Rv except 6b. Compounds 7a and 6b showed good activity against tested fungal pathogens. Compounds 7a and 7b were proven as the best bacterial agents. Molecular docking studies were in agreement with the in-vitro results. Docking analyses show that all the synthesized molecules bind to the target protein Mtb RNAP (PDB ID: 5UHC) fairly strongly. All the compounds were evaluated for their in vitro cytotoxicity effect using the MTT assay method against human cancer cell line MCF-7. The compounds demonstrated growth inhibitory effect on the cell line with significant IC50 values ranging between 8.20 and 34.45 µM. Most importantly, compound 7a displayed good binding affinity towards the tested protein with binding energy -7.30 kcal/mol and a stronger hydrogen bond distance of 2.2 Å with ASN-493 residue. Thus, the present research highlighted the potential role of novel piperazine derivatives as potential antitubercular, and antimicrobial candidates and further good research into optimization might result in the development of new antitubercular drug candidates.

Discovery of Natural Product-Based Fungicides (III): Semisynthesis and Biological Activity of N-Phenylpyrazole Sarisan Hybrids as Antifungal Agents.

Many phytopathogenic fungi can easily infect crops, resulting in crop yield reductions. In continuation of our efforts to develop natural product (NP)-based antifungal agents, a series of N-phenylpyrazole sarisan hybrids 6a-v were prepared via I2 -mediated oxidative cyclization, and their structures were determined by various spectral analyses including IR, 1 H-NMR and ESI-MS. Among all N-phenylpyrazole sarisan hybrids, compounds 6a, 6b, 6e, 6i, 6j and 6r exhibited more encouraging antifungal action against at least two phytopathogenic fungi than the reference fungicide hymexazol. Especially, 6a displayed really encouraging and broad-spectrum antifungal activity against F. graminearum, V. mali, and F. oxysporum f.sp.niveum with the EC50 values of 12.6±0.9, 18.5±0.2, and 37.4±1.8 µg/mL, respectively. Moreover, the structure-activity relationships (SARs) were also observed. Additionally, compounds 6a and 6e also exhibited relative low toxicity on normal LO2 cells. This study indicates that these N-phenylpyrazole sarisan hybrids would shed light on developing novel NP-based antifungal agents.

Design, synthesis and biological evaluation of novel evodiamine and rutaecarpine derivatives against phytopathogenic fungi.

Evodiamine and rutaecarpine are two alkaloids isolated from traditional Chinese herbal medicine Evodia rutaecarpa, which have been reported to have various biological activities in past decades. To explore the potential applications for evodiamine and rutaecarpine alkaloids and their derivatives, various kinds of evodiamine and rutaecarpine derivatives were designed and synthesized. Their antifungal profile against six phytopathogenic fungi Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Sclerotinia sclerotiorum, and Magnaporthe oryzae were evaluated for the first time. Furthermore, a series of modified imidazole derivatives of rutaecarpine were synthesized to investigate the structure-activity relationship. The results of antifungal activities in vitro showed that imidazole derivative of rutaecarpine A1 exhibited broad-spectrum inhibitory activities against R. solani, B. cinerea, F. oxysporum, S. sclerotiorum, M. oryzae and F. graminearum with EC50 values of 1.97, 5.97, 12.72, 2.87 and 16.58 µg/mL, respectively. Preliminary mechanistic studies showed that compound A1 might cause mycelial abnormalities of S. sclerotiorum, mitochondrial distortion and swelling, and inhibition of sclerotia formation and germination. Moreover, the curative effects of compound A1 were 94.7%, 81.5%, 80.8%, 65.0% at 400, 200, 100, 50 µg/mL in vivo experiments, which was far more effective than the positive control azoxystrobin. Significantly, no phytotoxicity of compound A1 on oilseed rape leaves was observed obviously even at a high concentration of 400 µg/mL. Therefore, compound A1 is expected to be a novel leading structure for the development of new antifungal agents.

Heat shock protein 90 (Hsp90)/Histone deacetylase (HDAC) dual inhibitors for the treatment of azoles-resistant Candida albicans.

Clinical treatment of candidiasis has suffered from increasingly severe drug resistance and limited efficacy. Thus, novel strategies to deal with drug resistance are highly desired to develop effective therapeutic agents. Herein, dual inhibition of heat shock protein 90 (Hsp90) and histone deacetylase (HDAC) was validated as a new strategy to potentiate efficacy of fluconazole against resistant Candida albicans infections. The first generation of Hsp90/HDAC dual inhibitors were designed as synergistic enhancers to treat azoles-resistant candidiasis. In particular, compound J5 exhibited fungal-selective inhibitory effects on Hsp90 and HDACs, leading to low toxicity and excellent in vitro (FICI = 0.266) and in vivo synergistic antifungal potency to treat fluconazole resistant candidiasis. Antifungal-mechanistic investigation revealed that compound J5 suppressed important virulence factors and down-regulated expression of resistance-associated genes. Therefore, Hsp90/HDAC dual inhibitors represent a new strategy for the development of novel antifungal therapeutics to combat azole-resistant candidiasis.

Antifungal, Antibacterial, and Cytotoxic Activities of Silver Nanoparticles Synthesized from Aqueous Extracts of Mace-Arils of Myristica fragrans.

In the present study, mace-mediated silver nanoparticles (mace-AgNPs) were synthesized, characterized, and evaluated against an array of pathogenic microorganisms. Mace, the arils of Myristica fragrans, are a rich source of several bioactive compounds, including polyphenols and aromatic compounds. During nano synthesis, the bioactive compounds in mace aqueous extracts serve as excellent bio reductants, stabilizers, and capping agents. The UV-VIS spectroscopy of the synthesized NPs showed an intense and broad SPR absorption peak at 456 nm. Dynamic light scattering (DLS) analysis showed the size with a Z average of 50 nm, while transmission electron microscopy (TEM) studies depicted the round shape and small size of the NPs, which ranged between 5-28 nm. The peaks related to important functional groups, such as phenols, alcohols, carbonyl groups, amides, alkanes and alkenes, were obtained on a Fourier-transform infrared spectroscopy (FTIR) spectrum. The peak at 3 keV on the energy dispersive X-ray spectrum (EDX) validated the presence of silver (Ag). Mace-silver nanoparticles exhibited potent antifungal and antibacterial activity against several pathogenic microorganisms. Additionally, the synthesized mace-AgNPs displayed an excellent cytotoxic effect against the human cervical cancer cell line. The mace-AgNPs demonstrated robust antibacterial, antifungal, and cytotoxic activity, indicating that the mace-AgNPs might be used in the agrochemical industry, pharmaceutical industry, and biomedical applications. However, future studies to understand its mode of action are needed.

Synthesis and in vitro biochemical properties, DNA binding and DNA cleavage ability of copper complexes of hydroxyflavone derivatives of novel organosulfur compounds as therapeutic agent.

Novel and synthetically essential flavonoids compounds containing the organosulfur moiety from Schiff bases, as well as their copper complexes, were synthesized from chrysin and 2-(phenylthio)aniline. These complexes were characterized using elemental analysis, mass spectrometry, electronic absorption spectroscopy, IR, 1H, and 13C NMR spectroscopy techniques. All the Cu(II) complexes exhibit square planar geometry. The in vitro antimicrobial activities of the investigated compounds were tested against the bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Klebsiella pneumoniae and fungal species, Aspergillus niger, Fusarium solani, Culvularia lunata, Rhizoctonia bataicola, and Candida albicans by serial dilution method. The DNA binding and DNA cleavage properties of copper complexes were studied. Free radical scavenging, superoxide dismutase, glutathione peroxidase, and antioxidant activities of the copper complexes have also been studied. In addition, using the egg albumin process, the in vitro anti-inflammatory efficacy of metal chelates was examined. Anti-tuberculosis and α-glucosidase inhibition activity were carried out from the prepared metal complexes. The flavonoid compounds containing the organosulfur moiety of Cu(II) complexes (1-8) exhibited better therapeutic agent.

Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment.

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti-Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

Glucosyl-1,2,3-triazoles derived from eugenol and analogues: Synthesis, anti-Candida activity, and molecular modeling studies in CYP-51.

This work describes the synthesis, anti-Candida, and molecular modeling studies of eighteen new glucosyl-1,2,3-triazoles derived from eugenol and correlated phenols. The new compounds were characterized by combined Fourier Transform Infrared, 1 H and 13 C nuclear magnetic resonance and spectroscopy of high-resolution mass spectrometry. The synthesized compounds did not show significant cytotoxicity against healthy fibroblast human cells (MCR-5) providing interesting selectivity indexes (SI) to active compounds. Considering the antifungal activity, nine compounds showed anti-Candida potential and the peracetylated triazoles 17 and 18 were the most promising ones. Eugenol derivative 17 was active against three species of Candida at 26.1-52.1 µM. This compound was four times more potent than fluconazole against Candida krusei and less toxic (SI > 6.6) against the MCR-5 cells than fluconazole (SI > 3.3) considering this strain. Dihydroeugenol derivative 18 showed similar activity to 17 and was four times more potent and less toxic than fluconazole against C. krusei. The deacetylated glucosides and non-glucosylated corresponding derivatives did not show considerable antifungal action, suggesting that the acetyl groups are essential for their anti-Candida activity. Molecular docking coupled with molecular dynamics showed that 14α-lanosterol demethylase is a feasible molecular target, since 17 and 18 could bind to this enzyme once deacetylated in vivo, thereby acting as prodrugs. Also, these studies demonstrated the importance of hydrophobic substituents at the phenyl ring.

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles.

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure-activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e-f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl2 or 5f with 3,4-Cl2). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC50 = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160-4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-ß-d-glucosaminide and 4-nitrophenyl-ß-d-N,N',N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing ß-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.

Discovery of a Novel Fusarium Graminearum Mitogen-Activated Protein Kinase (FgGpmk1) Inhibitor for the Treatment of Fusarium Head Blight.

Mitogen-activated protein kinase FgGpmk1 plays vital roles in the development and virulence of Fusarium graminearum (F. graminearum), the causative agent of Fusarium head blight (FHB). However, to date, the druggability of FgGpmk1 still needs verification, and small molecules targeting FgGpmk1 have never been reported. Here, we reported the discovery of a novel inhibitor 94 targeting FgGpmk1. First, a novel hit (compound 21) with an EC50 value of 13.01 µg·mL-1 against conidial germination of F. graminearum was identified through virtual screening. Then, guided by molecular modeling, compound 94 with an EC50 value of 3.46 µg·mL-1 was discovered, and it can inhibit the phosphorylation level of FgGpmk1 and influence the nuclear localization of its downstream FgSte12. Moreover, 94 can inhibit deoxynivalenol biosynthesis without any damage to the host. This study reported a group of FgGpmk1 inhibitors with a novel scaffold, which paves the way for the development of potent fungicides to FHB management.

Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation.

Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols (3a-3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and the evaluation of their antifungal activity. In silico prediction of biological activity with computer program PASS indicate that the compounds have a high novelty compared to the known antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k, followed by 3n. Their MIC values for different fungi were 22.1-184.2 and 71.3-199.8 µM, respectively. Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular docking studies on C. albicans sterol 14α-demethylase (CYP51) and DNA topoisomerase IV were used to predict the mechanism of antifungal activities. According to the docking results, the inhibition of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We also showed that most active compounds have a low cytotoxicity, which allows us to consider them promising antifungal agents for the subsequent testing activity in in vivo assays.

Identification of Thiazoyl Guanidine Derivatives as Novel Antifungal Agents Inhibiting Ergosterol Biosynthesis for Treatment of Invasive Fungal Infections.

Invasive fungal infections (IFIs) are fatal infections, but treatment options are limited. The clinical efficacies of existing drugs are unsatisfactory because of side effects, drug-drug interaction, unfavorable pharmacokinetic profiles, and emerging drug-resistant fungi. Therefore, the development of antifungal drugs with a new mechanism is an urgent issue. Herein, we report novel aryl guanidine antifungal agents, which inhibit a novel target enzyme in the ergosterol biosynthesis pathway. Structure-activity relationship development and property optimization by reducing lipophilicity led to the discovery of 6h, which showed potent antifungal activity against Aspergillus fumigatus in the presence of serum, improved metabolic stability, and PK properties. In the murine systemic A. fumigatus infection model, 6h exhibited antifungal efficacy equivalent to voriconazole (1e). Furthermore, owing to the inhibition of a novel target in the ergosterol biosynthesis pathway, 6h showed antifungal activity against azole-resistant A. fumigatus.

Lanosterol 14α-demethylase (CYP51)/histone deacetylase (HDAC) dual inhibitors for treatment of Candida tropicalis and Cryptococcus neoformans infections.

Invasive fungal infections remain a challenge due to lack of effective antifungal agents and serious drug resistance. Discovery of antifungal agents with novel antifungal mechanism is important and urgent. Previously, we designed the first CYP51/HDAC dual inhibitors with potent activity against resistant Candida albicans infections. To better understand the antifungal spectrum and synergistic mechanism, herein new CYP51/HDAC dual inhibitors were designed which showed potent in vitro and in vivo antifungal activity against C. neoformans and C. tropicalis infections. Antifungal mechanism studies revealed that the CYP51/HDAC dual inhibitors acted by inhibiting various virulence factors of C. tropicalis and C. neoformans and down-regulating resistance-associated genes. This study highlights the potential of CYP51/HDAC dual inhibitors as a promising strategy for the discovery of novel broad-spectrum antifungal agents.

Antivirulence activity and in vivo efficacy of a thiazole derivative against candidiasis.

Candida albicans is a pathogen equipped with a variety of commensal and virulence traits that help it colonize the microbiota and invade host tissue during infection. In this study, we investigated the potential anticandidal activity of 3-[2-(4-(4-methoxyphenyl)thiazol-2-yl)hydrazino)]butan-1-ol (MT), a thiazolylhydrazone compound synthesized by our group, and identified it as a promising antifungal agent. The activity of MT was evaluated in vitro and in vivo against C. albicans as well as its ability to inhibit virulence factors. For this, the ability of MT to inhibit the adhesion of C. albicans to human buccal epithelial cells and biofilm formation and filamentation was tested. In addition, the potential in vivo activity of MT was evaluated in murine models of oral candidiasis. Our results confirmed the antifungal activity of MT, with a minimal inhibitory concentration range of 0.5-2 µg/mL. Indeed, MT treatment in vitro decreased the expression of C. albicans genes involved in biofilm formation and morphogenesis and encoding hydrolytic enzymes, which was also confirmed through phenotypic observations. In addition, MT promoted a decrease in the colony forming units recovered from the tongues of mice with oral candidiasis. In this work, we present a potent antivirulence compound that shows potential for candidiasis therapy, especially for topical use.

Highly Active, Entirely Biobased Antimicrobial Pickering Emulsions.

We present the development of surfactant-free, silica-free and fully biobased oil-in-water antimicrobial Pickering emulsions, based on the self-assembly of ß-cyclodextrin and phytoantimicrobial oils (terpinen-4-ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio-based drug to treat fungal infection, but is less effective than petroleum-based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions. These emulsions are effective against fungi, Gram-positive and Gram-negative bacteria. The carvacrol emulsion charged with UA is +390 % and +165 % more potent against methicillin-resistant S. aureus (MRSA), compared to UA and azole-based commercial formulations. Moreover, this emulsion is up to +480 % more efficient that UA ointment against C. albicans. Finally, remarkable eradication of E. coli and MRSA biofilms was obtained with this environmental-friendly emulsion.

Design, synthesis, characterization, and biological evaluation of nicotinoyl thioureas as antimicrobial and antioxidant agents.

Addressed herein a series of thioureas starting from various amines and nicotinic acid have been synthesized. Notably, thiourea based scaffolds are increasingly employed in medicinal chemistry owing to their tunable physicochemical and structural properties. As well-known from the literature, the pyridine ring contains various biological properties, especially antimicrobial activity. Therefore, we performed the synthesis of biologically important thiourea derivatives containing pyridine ring. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and FT-IR. In the second part of the study, newly synthesized compounds were also tested in order to demonstrate their antimicrobial and antioxidant properties. All compounds exhibited moderate activity against all tested bacteria known to cause nosocomial infections, which have acquired resistance to many antibiotics, as compared to the standard antibiotics and also strong antioxidant properties. Therefore, they can be evaluated as possible seeds of agents in the treatment of bacterial infections and many health problems related to aging such as cancer, and neurodegenerative diseases.

Highly potent, broadly active antifungal agents for the treatment of invasive fungal infections.

Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins that have distinct advantages over peptides for pharmaceutical uses. Here we report the chemical optimization of bis-guanidine analogs focused on alterations of the central aryl core and the connection of it to the terminal guanidines. This effort resulted in the production of highly potent, broadly active compounds with low mammalian cell cytotoxicity that have comparable or improved antifungal activities over SOC agents. One optimal compound was also found to possess favourable in vitro pharmaceutical and off-target properties suitable for further development.

Antibacterial, Antifungal and Ecotoxic Effects of Ammonium and Imidazolium Ionic Liquids Synthesized in Microwaves.

Ionic liquids are increasingly used for their superior properties. Four water-immiscible ionic liquids (butyltriethylammonium bis(trifluoromethylsulfonyl)imide, octyltriethylammonium bis(trifluoromethylsulfonyl)imide, dodecyltriethylammonium bis(trifluoromethylsulfonyl)imide, butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and their water miscible precursors (bromides) were synthesized in a microwave reactor and by conventional heating. The best conditions for microwave-assisted synthesis concerning the yield and the purity of the product are proposed. The heating in the microwave reactor significantly shortened the reaction time. Biocide and ecotoxic effects of synthesized ionic liquids and their precursors were investigated. All tested compounds had at least a little effect on the growth or living of microorganisms (bacteria or mold). The precursor dodecyltriethylammonium bromide was found to be the strongest biocide, but posed a risk to the aquatic environment due to its relatively high EC50 value in the test with Vibrio fischeri. We assumed that apart from the alkyl chain length, the solubility in water, duration of action, or type of anion can influence the final biocide and ecotoxic effect.