Synthesis, characterization, absolute structural determination and antifungal activity of a new chlorinated aromatic avenaciolide analogue

BACKGROUND: Avenaciolide, a natural product isolated from Aspergillus avenaceus H. Smith, possesses several interesting biological properties, such as antifungal and antibacterial activities and inhibition of glutamate transport in mitochondria. In a study aiming to discover new compounds with antifungal activity, a bis‐γ‐lactone analogous to avenaciolide was prepared and characterized by elemental analysis, mass spectrometry, and infrared and NMR spectroscopy. RESULTS: The absolute structures of this compound and of the synthetic precursor (also a bis‐γ‐lactone) were determined by X‐ray diffraction analysis. The bis‐γ‐lactones synthesized crystallize in the orthorhombic space group P2₁2₁2₁, and the crystal packings are supported by C? H···O hydrogen bonds. The compound showed antifungal activity against Colletotrichum gloeosporioides (Penz.) Penz. & Sacc., while the synthetic precursor was inactive under the in vitro test conditions employed. CONCLUSION: The results indicate that it is not only the bis‐γ‐lactone skeleton that is important to antifungal activity. The latter also depends on the presence of the exocyclic double bond possibly due to a Michael addition type reaction with the fungal enzymes. Copyright © 2008 Society of Chemical Industry     

New melanin biosynthesis inhibitors and their structural similarities

Relationships between their activities as blast control agents, and their abilities to inhibit mycelial melanisation on a nutrient agar, are described for 103 substituted benzothiazol-2(3H)-ones, benzoxazol-2(3H)-ones, indolin-2-ones, quinolin-2(1H)-ones, 1,2,3,4-tetrahydroquinolin-2-ones, benzo-1,4-thiazin-3(2H)-ones and benz-1,4-oxazin-3(2H)-ones, and some corresponding thiones. Several compounds in the respective series had a high protective activity and an antimelanisation activity against the blast fungus Pyricularia oryzae; furthermore, there was a good correlation in both of these activities, indicating that these compounds belong to the group of melanin biosynthesis inhibitors. Structural similarities of these compounds can be identified as follows: (a) having a benzo-bicyclic ring system; (b) containing a nitrogen atom in one ring at a position alpha to the benzene ring system; and (c) substitution, at the ring nitrogen atom, at the peri position in the aromatic ring relative to the nitrogen atom, and at the position alpha to the nitrogen atom in the ring system, with a double bond such as in carbonyl and thiocarbonyl groups. Among the compounds that have been proposed as melanin biosynthesis inhibitors, the chemical structures of tricyclazole, pyroquilon, 4,5-dihydro-4-methyltetrazolo[1,5-a]quinazolin-5-one (PP-389), [1,2,4]-triazolo[4,3-a]quinoline and 1-methylquinolin-2(1H)-one exhibit the structural similarities described above; however, 4,5,6,7-tetrachlorophthalide, 2,3,4,5,6-pentachlorobenzyl alcohol and N-substituted-2,3,4,5-tetrachloro-6-(hydroxymethyl)benzamides do not have such similarities in their chemical structures.     

Synthesis, spectral characterization and antimicrobial activity of some transition metal(II) complexes with acetone p-amino acetophenone benzoylhydrazone

Complexes of the type [M(apabh)Cl] and [M(Hapabh)(H₂O)SO₄], where M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); Hapabh = acetone p-amino acetophenone benzoylhydrazone have been synthesized and characterized. Electronic spectra and μ_eff values suggest a square planar geometry for Co(II), Ni(II) and Cu(II) chloride complexes, whereas, octahedral geometry for the sulfato complexes. ESR data show isotropic spectra for [Cu(apabh)Cl] and axial spectra for [Cu(Hapabh)(H₂O)SO₄] and d_x²_−y² as the ground state for both Cu(II) complexes. The ligand acts as tridentate monobasic in all chloro complexes bonding through two >CN and a deprotonated enolate groups, whereas tridentate neutral in all sulfato complexes coordinating through two >CN and a >CO groups. Thermal analysis (TGA & DTA) of [Ni(apabh)Cl] complex shows a multi-step exothermic decomposition pattern. The complexes show a significant antifungal activity against Rizoctonia sp., Aspergillus sp. and Penicillium sp. and a considerably fair antibacterial activity against Pseudomonas sp. and Clostridium sp. The activity increases at higher concentration of the compound.     

Synthesis of D-glucosamine quaternary ammonium derivatives and evaluation of their antifungal activity together with aminodeoxyglucose derivatives against two wood fungi Coriolus versicolor and Poria placenta: structure-activity relationships

BACKGROUND: Structure–activity relationships are often reported in scientific studies. These may be employed in searching for new acceptable biocides to use against harmful microorganisms, because the biocides used hitherto encounter various problems, including lack of efficiency, high toxicity and persistence. Nowadays, scientists are trying to find new, environmentally acceptable biocides to replace these earlier biocides. Different compounds from renewable materials have been studied and have shown pronounced antifungal activity against wood fungi. These include aminopolysaccharide derivatives and different quaternary ammonium polymers. A biological study carried out with these products indicated a possible relationship between amino groups and differences in biological activity observed. RESULTS: In this study, an amino group was successively fixed to different carbon atoms of glucose, and glucosamine was also modified by both N‐alkylation and quaternisation. The impact of the amino group position on antifungal activity against two wood decay fungi was investigated. The amino group at the anomeric position showed the highest antifungal activity against both Coriolus versicolor Quel. and Poria placenta (Fr.) Cooke. Furthermore, the positive impact of both N‐alkylation and quaternisation on the growth of both strains was demonstrated. CONCLUSION: The anomeric position of the amino group and the N‐alkylation and quaternisation of amino sugars considerably increase the antifungal activity of these compounds. Copyright © 2010 Society of Chemical Industry     

Synthesis and insecticidal/acaricidal activity of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives

A series of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives has been synthesised and assayed for insecticidal/acaricidal activity. The assay indicated certain requirements for optimal insecticidal activity, which can be summarised as follows: (a) the substituents on the phenyl ring should possess hydrophobicity and electron‐withdrawing properties, and the sum of their volumes determines the level of activity; (b) the substituent at the 6‐position on the uracil ring should also possess electron‐withdrawing properties and hydrophobicity, together with the correct volume; (c) the 1‐position on the uracil ring should be unsubstituted for activity against Nephotettix cincticeps and Epilachna vigintioctopunctata, but substituents with length C3 to C4 may be optimal for activity against Tetranychus urticae; (d) certain substituents at the 5‐position of the uracil ring give activity against E vigintioctopunctata and T urticae, but not against N cincticeps; (e) a thiocarbonyl group at the 2‐position of the uracil ring is less effective than a carbonyl group. Of the compounds assayed, 3‐(2,6‐dichloro‐4‐trifluoromethylphenyl)‐6‐trifluoromethyluracil showed high activity against all the species assayed. © 2000 Society of Chemical Industry     

The antifungal activity of alkyl benzimidazol-2-ylcarbamates and related compounds

The fungistatic activity against Penicillium digitatum and Diplodia natalensis decreased slightly in ascending a homologous series of alkyl esters of benzimidazol-2-ylcarbamic acid from the methyl ester (carbendazim) to the pentyl ester; the hexyl and octyl esters were inactive. 2-(Acylamino)benzimidazoles were slightly less active than the analogous alkyl benzimidazol-2-ylcarbamates. Introduction of a methylene bridge between the benzimidazole ring and the 2-methoxycarbonylamino group abolished antifungal activity. Methylation of either the carbamate nitrogen or an imidazole nitrogen of carbendazim produced inactive compounds. Replacement of the benzimidazole ring of carbendazim with various other ring systems was accompanied by marked reduction in antifungal activity.     

Synthesis and bioactivity of novel sulfone derivatives containing 2,4-dichlorophenyl substituted 1,3,4-oxadiazole/thiadiazole moiety as chitinase inhibitors

The paper reported the synthesis and antifungal properties and mechanism of action of a series of 2-substituted methylthio-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole/thiadiazole and their corresponding sulfones. The preliminary biological test showed these compounds exhibit moderate to good antifungal activity. Particularly, the compounds 7g and 7c inhibited mycelia growth by approximately 50% (EC₅₀) at 2.6–59.2 μg/mL and 17.2–54.4 μg/mL respectively against nine kinds of fungi. The extent of inhibition induced by 7c on Rhizoctonia solani and underlying mechanism of action were studied in vitro. Docking simulation was performed to position selected compounds into the active site of family 18 chitinases. Variation in d-GlcNAc content and chitinase activity indicated that 7c can act as chitinase inhibitor for controlling fungal pathogens in plants.     

Pyrethroid insecticides derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal

Fourteen oxime ethers and eleven other unsaturated compounds derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal were synthesised and their insecticidal activity against Musca domestica, Locusta migratoria, Dysdercus cingulatus, Aedes aegypti, Plutella xylostella, Drosophila melanogaster, Tetranychus urticae and Spodoptera littoralis tested. Structural variations including chain length, branching and unsaturation of the oxime ether O-alkyl group and substituent exchange at the carbon-carbon double bond of the unsaturated compounds were made in order to examine the structure-activity relationship. All biological activities were compared with the activity of the ether pyrethroid MTI-500.     

Activity of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones and related compounds against Musca domestica

A series of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones has been prepared and their toxicities assessed against Musca domestica. By comparison with analogous compounds having saturated 2-alkyl substituents, or unsaturated substituents with an unconjugated double bond (e.g. lapachol), it was demonstrated that the α-unsaturation of the substituent is responsible for a significant increase in the toxicity. The effect of the compounds against several other insect species and Tetranychus urticae follows completely different patterns.     

Evaluation of novel sulfonylurea derivatives with a fused heterocyclic moiety as paddy herbicides that control sulfonylurea‐resistant weeds

Herbicidal activity and acetolactate synthase (ALS) inhibition of sulfonylurea derivatives with a fused heterocyclic moiety bonded to a sulfonyl group were investigated. Some compounds that had an imidazo[1,2‐b]pyridazine moiety substituted at the 2‐position by chlorine or methyl controlled sulfonylurea‐resistant (SU‐R) weeds and showed inhibitory activity to ALS prepared from SU‐R Schoenoplectus juncoides shoot. There was a correlation between in vitro and whole‐plant herbicidal activity of the compounds mentioned above against SU‐R Schoenoplectus juncoides. Among them 1‐(2‐chloro‐6‐propylimidazo[1,2‐b]pyridazin‐3‐ylsulfonyl)‐3‐(4,6‐dimethoxypyrimidin‐2‐yl)urea, propyrisulfuron, was selected for further evaluation. Propyrisulfuron effectively controlled paddy weeds at doses of 70 and 140 g a.i. ha^?1 with good rice selectivity in a field trial.     

Allylamine antimycotics: Recent trends in structure—activity relationships and syntheses

Methods developed for the synthesis of terbinafine-related allylamine antimycotics are reviewed. The synthesis of the en-yne side chains were generally accomplished by means of organometallic reactions. The use of Pd⁰-catalysed coupling reactions allowed easy access to derivatives bearing sensitive side-chain substituents. As examples, four metabolites of terbinafine were prepared via this procedure. Investigations with the carbon analogue of terbinafine revealed that, within the allylamine antimycotics, the nitrogen appears to be necessary for penetration by the drug into the fungal cell. Replacement of the naphthalene moiety of terbinafine by optionally substituted benzo[b]thiophenes led to a number of derivatives with high antifungal activity. A series of benzo[b]thienyl compounds with the side chain at position 7 and different substituents at position 3 showed significantly increased activity against Candida albicans in vitro. In particular, the 3-chloro derivative with the allylamine side chain at position 7(SDZ 87–469) proved to be the most potent allylamine antimycotic reported to this date. Two novel types of lead structures, the homopropargylamines and the benzylamines show very high activity in vitro.     

β-aminobutyric acid protects <Emphasis Type="Italic">Brassica napus</Emphasis> plants from infection by <Emphasis Type="Italic">Leptosphaeria maculans.</Emphasis> Resistance induction or a direct antifungal effect?

Resistance to infection in plants can be induced by treatment with various chemicals. One such compound is β-aminobutyric acid (BABA). Its positive effect on disease resistance has been noted in several pathosystems. Here we demonstrate that treatment with BABA protects Brassica napus plants from infection by the fungal pathogen Leptosphaeria maculans. Surprisingly, BABA also displayes in vitro antifungal activity against L. maculans with EC₅₀ similar to the fungicide tebuconazole. Both spore germination and hyphal growth were affected. The toxic effect can be reverted by addition of trypton to the culture medium. We hypothesised that BABA might inhibit inorganic nitrogen assimilation. Suppression of disease progression in plants and antifungal activity in vitro was weaker for α-aminobutyric acid and negligible for γ-aminobutyric acid. In contrast to a resistance inducer benzothiadiazole, the effect of BABA on disease development was nearly independent of the timing of treatment, indicating possible antifungal activity in planta. On the other hand, quantification of multiple hormones and an expression analysis have shown that treatment with BABA induces a synthesis of salicylic acid (SA) and expression of SA marker gene PR-1, but no evidence was observed for priming of SA responses to L. maculans. While we have not conclusively demonstrated how BABA suppresses the disease progression, our results do indicate that antifungal activity is another mechanism by which BABA can protect plants from infection.     

Structure–biological activity relationships in triterpenic saponins: the relative activity of protobassic acid and its derivatives against plant pathogenic fungi

BACKGROUND: Triterpenic saponins from Sapindus mukorossi Gaertn. and Diploknema butyracea JF Gmelin were evaluated for in vitro antifungal activity against four phytopathogenic fungi. The study of the structure–antifungal activity relationships of protobassic acid saponins was widened by including semi‐synthetic derivatives. RESULTS: Diploknema butyracea saponins exhibited significant antifungal activity against three fungi (ED₅₀ 230–455 µg mL^?1), whereas S. mukorossi saponin was effective against two fungi (ED₅₀ 181–407 µg mL^?1). The n‐butanol extract after preparative HPLC separation provided two saponins from D. butyracea saponin mixture: 3‐O‐[β‐D ‐glucopyarnosyl‐β‐D ‐glucopyranosyl]‐16‐α‐hydroxyprotobassic acid‐28‐O‐[arabinopyranosyl‐glucopyranosyl‐xylopyranosyl]‐arabinopyranoside (MI‐I), and 3‐O‐β‐D ‐glucopyranosyl‐glucopyranosyl‐glucopyranosyl‐16‐α‐hydroxyprotobassic acid‐28‐O‐[arabinopyranosyl‐xylopyranosyl‐arabinopyranosyl]‐apiofuranoside (MI‐III). The single saponin extracted from S. mukorossi saponin mixture was identified as 3‐O‐[O‐acetyl‐β‐D ‐xylopyranosyl‐β‐D ‐arabinopyranosyl‐β‐D ‐rhamnopyranosyl] hederagenin‐28‐O[β‐D ‐glucopyranosyl‐β‐D ‐glucopyranosyl‐β‐D ‐rhamnopyranosyl] ester (SM‐I). Monodesmosides resulting from the partial degradation of hederagenin and hydroxyprotobassic acid bisdesmosides exhibited significant reduction in antifungal effect. Further removal of sugar moiety yielded complete loss in activity. The antifungal activity of the triterpenic saponins was associated with their aglycone moieties, and esterification of the hydroxyl group led to change in antifungal activity. CONCLUSION: Sapindus mukorossi saponin, which is effective against Rhizoctonia bataticola (Taub.) Briton Jones and Sclerotium rolfsii Sacc., can be exploited for the development of a natural fungicide. A sugar moiety is a prerequisite for the antifungal activity of triterpenic saponin. Copyright © 2010 Society of Chemical Industry     

The antifungal activity of some sulphonyl derivatives of isoxazole,pyrazole, thiazole and thiophene

Fifty-three heterocyclic sulphonyl derivatives including eight sulphonamides, three sulphonyl azides, nine sulphonohydrazides and twenty sulphonohydrazones of substituted thiophenes, and a smaller range of analogous isoxazoles pryazoles and thiazoles, were tested as potential fungicides in a simple screening procedure against Mucor mucedo, Septoria nodorum, Trichoderma viride, Chaetomium globosum and Aspergillus niger. Several thiophene-2-sulphonyl based compounds exhibited a high level of antifungal activity at 100 mg litre^?1 against the five test species, especially the mono-halogen-substituted sulphonamides and sulphonohydrazines, in which a single chlorine or bromine atom was substituted in the para position of an attached phenyl ring. The most active compound, against all five species of fungus was N-(4-chlorophenyl)-N-(trichloromethylthio) thiophene-2-sulphonamide which had average MIC₅₀ and MIC₁₀₀ values of 86 and 180 μmol respectively. (MIC₅₀ and MIC₁₀₀ values are, respectively, the concentrations required to inhibit fungal growth by 50% and to inhibit it totally.) In general, the isoxazole analogues of the thiophene-2-sulphonyl compounds exhibited a much lower fungitoxic activity, whilst the pyrazole and thiazole based compounds had little or no activity. Compared with the other results, the considerable activity shown by 4-[2′-(3,4-dichlorobenzylidene)hydrazinosulphonyl]thiophene-2-carboxylic acid was unexpected.     

Synthesis and herbicidal activities of novel 3-(substituted benzyloxy or phenoxy)-6-methyl-4-(3-trifluoromethylphenyl)pyridazine derivatives

BACKGROUND: 4‐(3‐Trifluoromethylphenyl)pyridazine represents a new series of compounds with bleaching and herbicidal activities. RESULTS: A total of 43 novel 3‐(substituted benzyloxy or phenoxy)‐6‐methyl‐4‐(3‐trifluoromethylphenyl)pyridazine derivatives were synthesised, and their bleaching and herbicidal activities were evaluated through Spirodela polyrrhiza and greenhouse tests. Some compounds exhibited excellent herbicidal activities, even at a dose of 7.5 g ha^?1. CONCLUSION: The results showed that a substituted phenoxy group at the 3‐position of the pyridazine ring and the electron‐withdrawing group at the para ‐position on the benzene ring were essential for high herbicidal activity. Copyright © 2011 Society of Chemical Industry     

Synthesis of substituted benzyl 2-methyl-2-phenylpropyl ethers and their moth-proofing activity on wool against larvae of Anthrenus fasciatus

Synthesis of new moth-proofing agents is necessary to overcome the damage caused by clothes moths and carpet beetles to hosiery and upholstery. In the present paper substituted benzyl 2-methyl-2-phenylpropyl ethers were synthesised and evaluated for moth-proofing activity. Two compounds were found to provide protection against larvae of Anthrenus fasciatus at levels of 1.0 and 10 g kg⁻¹ respectively. The introduction of a methyl group in the para position of the benzene ring attached to C₂ of the 2-methylpropyl chain (ring A) increased moth-proofing activity. The introduction of a phenoxy ring at the meta position of the benzyl nucleus (ring B) also increased activity, while the presence of a nitro group on the benzyl nucleus (ring B) decreased activity. © 1999 Society of Chemical Industry     

Synthesis and precocious-metamorphosis-inducing activity of 3-pyridyl ethers

A new series of 5-(substituted phenoxy)pentyl 3-pyridyl ethers induced precocious metamorphosis in larvae of the silkworm, Bombyx mori. Both 2- and 4-pyridyl ethers were inactive, indicating that the 3-pyridine moiety was essential for the activity. Octyl, dodecyl and farnesyl 3-pyridyl ethers had no activity. Among the compounds tested so far, 5-(4-propylphenoxy)pentyl 3-pyridyl ether showed the highest activity. The activity fell off with increasing or decreasing length of the carbon chain between two oxygen atoms. Introduction of a methyl group at the 6 position of the pyridine ring completely eliminated the activity. Precocious metamorphosis induced by 3-pyridyl ethers was fully reversible by a simultaneous application of a small amount of tebufenozide, an ecdysteroid agonist, or methoprene, a JH agonist. © 1998 SCI.     

Mode of action of chitosan coating on anthracnose disease control in papaya

The effect of a chitosan coating on antifungal activity and rate of respiration, chitinase and β, 1-3 glucanase activities with reference to papaya variety ‘Rathna’ was investigated. One percent chitosan, extracted from locally available prawn waste, was selected as the effective concentration to inhibit spore germination via a series of experiments on potato dextrose agar. Rate of respiration and the concentration of CO₂ in the internal cavity of chitosan-treated and untreated papaya were tested via gas chromatography. Chitinase and β,1-3 glucanase activities were tested in peel samples using gel diffusion and spectrophotometric assays, respectively. Complete inhibition of spore germination was observed in-vitro at treatments of 1% chitosan and above. This concentration significantly (P < 0.05) reduced both disease incidence and severity on inoculated fresh papaya. Significant (P < 0.05) decrease was observed in rate of respiration while internal CO₂ concentration of the fruit increased (P < 0.05) with the chitosan treatment. Chitinase and β,1-3 glucanase activities of papaya variety Rathna subjected to chitosan treatment were much higher than in the untreated control. Chitosan shows antifungal activity to the anthracnose disease causing fungus and stimulates the defense response on the papaya peel by increasing the chitinase and β,1-3 glucanase activities. The antifungal activity of chitosan could be attributed to the induction of elicitation activity due to these defense enzymes. It also forms a semi-permeable coating around the fruit and extends storage life of papaya by reducing the rate of respiration and delaying ripening.     

Structure–Activity Relationships of Herbicidal Aryltriazolinones

A series of substituted aryltriazolinones, known to inhibit protoporphyrinogen oxidase, were prepared and their structure–activity requirements at positions 4 and 5 of the aromatic ring investigated. A QSAR equation obtained for substituents at the 5 position identified the hydrophobicity term π and the Sterimol minimum width B₁ as the two parameters affecting in-vitro biological activity. Greenhouse pre-emergence activity correlated with in-vitro activity and the hydrophobicity term π of the substituent at that position. It was found that the phenoxy-4-oxyacetate group at aromatic position 5 was an outlier and had to be considered separately. SAR analysis of substituents at aromatic position 4 revealed that two different models were required to explain all observed substituent effects. In the first model, where the 5 position was occupied by hydrogen, the 4-chlorobenzyloxy group at aromatic position 4 gave the best compound. The second model, where the 5 position of the aromatic ring was occupied by a group other than hydrogen, resulted in a QSAR equation, previously derived, which links substituent effects at position 4 with π and with the electronic para inductive term F_p. In this model the chloro group provides optimum biological activity. The need to separate the aryltriazolinone herbicides into several different classes in order to explain their substituent effects at aromatic positions 4 and 5 could be rationalized if more than one binding conformation, within the same binding site, is possible. © 1997 SCI     

Purification, N-terminal amino acid sequencing and antifungal activity of chitinases from pepper stems treated with mercuric chloride

Different isoforms of chitinases were purified from pepper (Capsicum annuumL. cv. Hanbyul) stems treated with mercuric chloride. The acidic isoform a1 (69kDa, pI5.0), basic isoforms b1 (32kDa, pI9.0) and b2 (22kDa, pI9.1) were purified by chitin-affinity chromatography, with subsequent electroelution from nondenaturing polyacrylamide gel electrophoresis (PAGE) gels. The acidic isoform a1 has chitin-binding properties, but no antifungal activity. The basic isoforms b1 and b2 contain high ratios of cysteine and glycine at the N-terminal chitin-binding domain, exhibit chitinase activity, and show antifungal activities againstColletotrichum gloeosporioides, Fusarium oxysporumf.sp.cucumerinum, Magnaporthe grisea, andTrichoderma viride in vitro.Moreover, their antifungal activity shows a high degree of specificity to filamentous fungi. The chitinases b1 and b2 show a high sequence identity in their N-terminal residues with those from wheat, tobacco, potato, rice andArabidopsis thaliana.None of the purified isoforms of chitinases inhibited hyphal growth of the Oomycete fungus which lacks chitinPhytophthora capsici. In contrast, zoospore germination and germ tube elongation ofP. capsiciwere effectively inhibited by treatment with b1 and b2.