Putting the brakes on tumorigenesis with snake venom toxins: New molecular insights for cancer drug discovery.

Cancer cells exhibit molecular characteristics that confer them different proliferative capacities and survival advantages to adapt to stress conditions, such as deregulation of cellular bioenergetics, genomic instability, ability to promote angiogenesis, invasion, cell dormancy, immune evasion, and cell death resistance. In addition to these hallmarks of cancer, the current cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. These aspects highlight the need to identify promising therapeutic targets for new generations of anti-cancer drugs. Toxins isolated from snake venoms are a natural source of useful molecular scaffolds to obtain agents with a selective effect on cancer cells. In this article, we discuss the recent advances in the molecular mechanisms of nine classes of snake toxins that suppress the hallmarks of cancer by induction of oxidative phosphorylation dysfunction, reactive oxygen species-dependent DNA damage, blockage of extracellular matrix-integrin signaling, disruption of cytoskeleton network and inhibition of growth factor-dependent signaling. The possible therapeutic implications of toxin-based anti-cancer drug development are also highlighted.

Assessment of the Long-Range NMR C,H Coupling of a Series of Carbazolequinone Derivatives.

Synthesis, the complete 1H- and 13C-NMR assignments, and the long-range C,H coupling constants (nJC,H) of some hydrogen-deficient carbazolequinones, assessed by a J-HMBC experiment, are reported. In these molecules, the protons, used as entry points for assignments, are separated by several bonds with non-protonated atom carbons. Therefore, the use of long-range NMR experiments for the assignment of the spectra is mandatory; we used HSQC and HMBC. On the other hand, the measured heteronuclear (C,H) coupling constants 2J to 5J) allow us to choose the value of the long-range delay used in the HMBC experiment less arbitrarily in order to visualize a desired correlation in the spectrum. The chemical shifts and the coupling constant values can be used as input for assignments in related chemical structures.

Novel N-benzoylimidazolium ionic liquids derived from benzoic and hydroxybenzoic acids as therapeutic alternative against Biofilm-forming bacteria in skin and soft-tissue infections.

The skin and soft tissue infections (SSTIs) -producing pathogens have acquired resistance to a wide range of antimicrobials, thus it is highly relevant to have new treatment alternatives. In this study, we report the synthesis, characterization, and antibacterial activity of three novel series of ionic liquids (ILs) derived from benzoic and hydroxybenzoic acids, with different lengths of the alkyl chain. The minimum inhibitory concentration (MIC) were tested in Gram-positive: Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes, and Gram-negative: Acinetobacter baumannii and Escherichia coli, showing a MIC range of 0.01562-2.0 mM, with the activity varying according to the aromatic ring functionalization and the length of the alkyl chains. Regarding the antibiofilm activity, different efficacy was observed among the different ILs, some of them presenting antibiofilm activities close to 80% as in the case of those derived from syringic acid with an alkyl chain of six carbon atoms against Pseudomonas aeruginosa. Furthermore, the cell viability in HaCaT cells was determined, showing a half maximal effective concentration (EC50) values higher than the MIC values. The antimicrobial and antibiofilm results, along with not producing cellular toxicity at the MIC values shows that these ILs could be a promising alternative against SSTIs.

Study of the Electrochemical Behavior of N-Substituted-4-Piperidones Curcumin Analogs: A Combined Experimental and Theoretical Approach.

The electrochemical behavior of N-methyl- and N-benzyl-4-piperidone curcumin analogs were studied experimentally and theoretically. The studied compounds present different substituents at the para position in the phenyl rings (-H, -Br, -Cl, -CF3, and -OCH3). We assessed their electrochemical behavior by differential pulse and cyclic voltammetry, while we employed density functional theory (DFT) M06 and M06-2x functionals along with 6-311+G(d,p) basis set calculations to study them theoretically. The results showed that compounds suffer a two-electron irreversible oxidation in the range of 0.72 to 0.86 V, with surface concentrations ranging from 1.72 × 10-7 to 5.01 × 10-7 mol/cm2. The results also suggested that the process is diffusion-controlled for all compounds. M06 DFT calculations showed a better performance than M06-2x to obtain oxidation potentials. We found a good correlation between the experimental and theoretical oxidation potential for N-benzyl-4-piperidones (R2 = 0.9846), while the correlation was poor for N-methyl-4-piperidones (R2 = 0.3786), suggesting that the latter suffer a more complex oxidation process. Calculations of the BDEs for labile C-H bonds in the compounds suggested that neither of the two series of compounds has a different tendency for a proton-coupled electron transfer (PCET) oxidation process. It is proposed that irreversible behavior is due to possible dimerization of the compounds by Shono-type oxidation.

Antimicrobial properties of novel ionic liquids derived from imidazolium cation with phenolic functional groups.

Bacterial infections are nowadays among the major threats to public health worldwide. Thus, there is an urgent and increased need for new antimicrobial agents. As a result, the exploration of the antimicrobial properties of different substances including ionic liquids (ILs) has recently attracted great attention. The present work is aimed at evaluating how the addition of halogens and hydrophobic substituents on alkylimidazolium units of ILs as well as the increase in their chain lengths affects the antimicrobial properties of such ILs. After their synthesis, the antibacterial activities of these compounds against Pseudomona aeruginosa, Escherichia coli, and Staphylococcus aureus are determined by measuring their minimal inhibitory concentrations (MICs). Key features in ILs-membrane interactions are also studied using long-term all-atom molecular dynamics simulations (MDs). The results show that these ILs have good antibacterial activity against S. aureus, E. coli, and P. aeruginosa, with MIC values range from <7.81 to 62.50 µM. The antimicrobial property of tert-butyl N-methylphenolimidazolium salts (denoted as 8b and 8c) is particularly better with MIC values of < 7.81 µM. The antibacterial efficacy is also found to depend on the alkyl chain length and substituents on the phenolic ring. Finally, MDs done for ILs in a phosphatidylcholine (POPC) bilayer show key features in the mechanism of IL-induced membrane disruption, where the ILs are inserted as clusters into one side of the bilayer until saturation is reached. This insertion increases "leaflet strain" up to critical threshold, likely triggering the morphological disruption of the membranes in the microbes.

An acylhydroquinone derivative produces OXPHOS uncoupling and sensitization to BH3 mimetic ABT-199 (Venetoclax) in human promyelocytic leukemia cells.

Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 µM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial ß-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.

Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels.

Platelet activation plays a key role in cardiovascular diseases. The generation of mitochondrial reactive oxygen species (ROS) has been described as a critical step required for platelet activation. For this reason, it is necessary to find new molecules with antiplatelet activity and identify their mechanisms of action. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces mitochondrial overproduction of ROS. In this work, the antiplatelet effect of MitoQ through platelet adhesion and spreading, secretion, and aggregation was evaluated. Thus MitoQ, in a non-toxic effect, decreased platelet adhesion and spreading on collagen surface, and expression of P-selectin and CD63, and inhibited platelet aggregation induced by collagen, convulxin, thrombin receptor activator peptide-6 (TRAP-6), and phorbol 12-myristate 13-acetate (PMA). As an antiplatelet mechanism, we showed that MitoQ produced mitochondrial depolarization and decreased ATP secretion. Additionally, in platelets stimulated with antimycin A and collagen MitoQ significantly decreased ROS production. Our findings showed, for the first time, an antiplatelet effect of MitoQ that is probably associated with its mitochondrial antioxidant effect.

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands.

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

N-alkylimidazolium Salts Functionalized with p-Coumaric and Cinnamic Acid: A Study of Their Antimicrobial and Antibiofilm Effects.

The bacterial resistance to antibiotics has compromised the therapies used for bacterial infections. Nowadays, many strategies are being carried out to address this problem. Among them, the use of natural compounds like cinnamic and p-coumaric acids stands out. Nevertheless, their utilization is limited because of their unfavorable physicochemical properties. Due to the lack of new therapeutic alternatives for bacterial infections, novel strategies have emerged, such as the use of ionic liquids; given that they can show a broad spectrum of antibacterial activity, this is why we herein report the antibacterial and antibiofilm activity of a series of N-alkylimidazolium salts functionalized with p-coumaric and cinnamic acids. The results from this study showed better antibacterial activity against Gram-positive bacteria, with a predominance of the salts derived from coumaric acid and a correlation with the chain length. Additionally, a lower efficacy was observed in the inhibition of biofilm formation, highlighting the antibiofilm activity against Staphylococcus aureus, which decreased the production of the biofilm by 52% over the control. In conclusion, we suggest that the salts derived from p-coumaric acid are good alternatives as antibacterial compounds. Meanwhile, the salt derived from cinnamic acid could be a good alternative as an antibiofilm compound.

Detoxification Mechanism of 8,8-Dimethyl-3-[(R-phenyl)amino]-1,4,5(8H)-naphthalentrione Derivatives by Botrytis cinerea.

The effect of 8,8-dimethyl-3-[(R-phenyl)amino]-1,4,5(8H)-naphthalentrione derivatives (compounds 1⁻13) on the mycelial growth of Botrytis cinerea was evaluated. The fungitoxic effect depended on the substituent and its position in the aromatic ring. Compounds substituted with halogens in meta and/or para positions (compounds 3, 4, 5 and 7), methyl (compounds 8 and 9), methoxyl (compounds 10 and 11), or ethoxy-carbonyl groups (compound 12) presented higher antifungal activity than compound 1, which had an unsubstituted aromatic ring. In addition, compounds with halogens in the ortho position, such as compounds 2 and 6, and a substitution with an acetyl group in the para position (compound 13) were less active. The role of the ABC efflux pump Bctr B-type as a defense mechanism of B. cinerea against these naphthalentrione derivatives was analyzed. This pump could be involved in the detoxification of compounds 2, 6, and 13. On the contrary, this mechanism would not participate in the detoxification of compounds 1, 7, 9 and 12. Finally, the biotransformation of compound 7 by B. cinerea was studied. A mixture of two biotransformed products was obtained. One of them was compound 7A, which is reduced at C1 and C4, compared to compound 7. The other product of biotransformation, 7B, is oxidized at C7.

Assessing Parameter Suitability for the Strength Evaluation of Intramolecular Resonance Assisted Hydrogen Bonding in o-Carbonyl Hydroquinones.

Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB's with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O…H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ΔEij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ΔEij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental ¹H-NMR chemical shifts for the IMHB, with R² values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R².

Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine.

Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.

Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core.

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 µM and 20.2 ± 0.9 µM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1A R/SERT.

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT1A R) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT1A R (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug-target interactions, which allowed rationalizing the observed affinities.

Experimental and Theoretical Reduction Potentials of Some Biologically Active ortho-Carbonyl para-Quinones.

The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The first and second one-electron reduction potentials of the quinones were determined using cyclic voltammetry and correlated with those calculated by density functional theory (DFT) using three different functionals, BHandHLYP, M06-2x and PBE0. The differences among the experimental reduction potentials were explained in terms of structural effects on the stabilities of the formed species. DFT calculations accurately reproduced the first one-electron experimental reduction potentials with R² higher than 0.94. The BHandHLYP functional presented the best fit to the experimental values (R² = 0.957), followed by M06-2x (R² = 0.947) and PBE0 (R² = 0.942).

A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding.

A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules.

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation.

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3ADP), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells.

Protonation Sites, Tandem Mass Spectrometry and Computational Calculations of o-Carbonyl Carbazolequinone Derivatives.

A series of a new type of tetracyclic carbazolequinones incorporating a carbonyl group at the ortho position relative to the quinone moiety was synthesized and analyzed by tandem electrospray ionization mass spectrometry (ESI/MS-MS), using Collision-Induced Dissociation (CID) to dissociate the protonated species. Theoretical parameters such as molecular electrostatic potential (MEP), local Fukui functions and local Parr function for electrophilic attack as well as proton affinity (PA) and gas phase basicity (GB), were used to explain the preferred protonation sites. Transition states of some main fragmentation routes were obtained and the energies calculated at density functional theory (DFT) B3LYP level were compared with the obtained by ab initio quadratic configuration interaction with single and double excitation (QCISD). The results are in accordance with the observed distribution of ions. The nature of the substituents in the aromatic ring has a notable impact on the fragmentation routes of the molecules.

A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions.

In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f⁺) and Parr (P⁺) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,ß-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity.

Action mechanism for 3ß-hydroxykaurenoic acid and 4,4-dimethylanthracene-1,9,10(4H)-trione on Botrytis cinerea.

The mechanism of action of the diterpenoid 3ß-hydroxykaurenoic acid and the anthraquinone 4,4-dimethylanthracene-1,9,10(4H)-trione on the phytopathogenic fungus Botrytis cinerea was studied. The effect of both compounds on the respiratory process and on the membrane integrity of B. cinerea was evaluated. The results showed that 3ß-hydroxykaurenoic acid inhibited the growth of this fungus by disrupting the plasmatic membrane. This compound also partially affected oxygen consumption of B. cinerea germinating conidia. Conversely, 4,4-dimethylanthracene-1,9,10(4H)-trione did not produce membrane disruption of B. cinerea. The effect of this compound on mycelial growth was notably increased by the presence of an inhibitor of the cyanide-resistant respiration pathway. It also was shown that the anthraquinone inhibited oxygen consumption by about 80%; therefore this compound would act as a potent inhibitor of the cytochrome pathway of the respiratory chain to exert its antifungal effect.