Active Antifungal Compounds Research Articles

Natural Phthalate Derivatives from the Bacterium <i>Burkholderia cepacia</i> K87

In continuation of our screening of antifungal active compounds from the fermentation extracts of soil borne bacteria Burkholderia cepacia K87 afforded three phthalate derivatives, dibutyl phthalate (1), dioctyl phthalate (2), and phthalate ester of alkylated 9-hydroxynonanoic acid (3). Compound 3 was reported first time. These phthalate derivatives were found to be marginally active or inactive against a number of bacteria and fungi. Keywords: Burkholderia cepacia K87; Phthalate; Antifungal. © 2010 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.DOI: 10.3329/jsr.v2i1.2696 J. Sci. Res. 2 (1), 191-195 (2010)

Novel Oxidized Derivatives of Antifungal Pyrrolnitrin from the Bacterium Burkholderia cepacia K87

The screening of antifungal active compounds from the fermentation extracts of soil-borne bacterium Burkholderia cepacia K87 afforded pyrrolnitrin (1) and two new pyrrolnitrin analogs, 3-chloro-4-(3-chloro-2-nitrophenyl)-5-methoxy-3-pyrrolin-2-one (2) and 4-chloro-3-(3-chloro-2-nitrophenyl)-5-methoxy-3-pyrrolin-2-one (3). Pyrrolnitrin showed strong antifungal activity against Rhizoctonia solani but the analogs (2 and 3) were found to be marginally active. The isolates, 2 and 3, are believed to be biodegraded derivatives of pyrrolnitrin.

Fengycin antibiotics isolated from B-FS01 culture inhibit the growth ofFusarium moniliformeSheldon ATCC 38932

Strain B-FS01, isolated from rape (Brassica napus) stem infected by Slerotinia sclerotiorum and identified as Bacillus subtilis, exhibited predominantly antagonistic activities against Fusarium moniliforme Sheldon ATCC 38932. Antifungal active compounds (AAC) were isolated and purified from the cultures of strain B-FS01 against ATCC 38932. The HPLC/electron spray ionization/collision-induced dissociation mass spectrum of AAC revealed a cluster of fengycin homologues containing fengycins A, fengycins B and a new type of fengycin. Further toxic assay of AAC in vitro against F. moniliforme indicated that AAC could strongly inhibit the growth of both mycelia and spores. In addition, treatment with AAC significantly modified the maize seed infection by ATCC 38932.

Identification of novel cell-wall active antifungal compounds

Fungal infections of humans and other animals are serious and often life threatening, especially in immunocompromised patients. One difficulty in treating fungal disease is the limited arsenal of antifungal compounds. The recent regulatory approval of three cell-wall active antifungal compounds encourages the search for additional clinical candidates that inhibit fungal cell wall formation. We have screened a small portion of a unique chemical library and have found eight compounds that appear to be inhibitors of fungal cell wall assembly.

Bioautography indicates the multiplicity of antifungal compounds from twenty-four southern African Combretum species (Combretaceae)

Dried ground leaves of 24 Combretum spp were extracted with hexane, dichloromethane, acetone and methanol and analysed by bioautography to determine the number of antifungal compounds against five animal fungal pathogens (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Microsporum canis and Sporothrix schenckii). There was some similarity in the chemical composition of the non-polar components of extracts using extractants of varying polarity. Acetone extracted the most antifungal compounds from Combretum spp. Combretum spp. in the section Hypocrateropsis, C. celastroides ssp. celastroides and C. clelastroides ssp. orientale had 62 different antifungal zones of inhibition compared to the 7 to 8 of C. microphyllum and C. paniculatum in the Connivetaia section. C. collinum subspecies were not active against all the tested pathogens. C. neoformans was the most sensitive organism against all Combretum species, with 367 zones of inhibition using different TLC solvent systems and extracts. A. fumigatus was the most resistant (192 zones of inhibition). The antifungal activity and number of active antifungal compounds were high enough to consider the use of extracts for clinical application and to isolate antifungal compounds from the extracts. Based on the Rf values of the antifungal compounds determined using solvents of varying polarity, activity is not only be attributable to tannins found in Combretum extracts as was previously postulated.

Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin

A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethylsufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD50 = 2.9072 × 10− 4 and 3.2844 × 10− 4 M, respectively, displayed potent cytotoxic activity against Artemia salina

Strategies for Total and Diversity‐Oriented Synthesis of Natural Product(‐like) Macrocycles

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis, Antimicrobial and Antifungal Activity of a New Class of Spiro pyrrolidines

A new class of spiro pyrrolidines, dispiro[oxindole-cyclohexanone]pyrrolidines, 1 dispiro[oxindole-tetrahydronaphthalen-1-one]pyrrolidines, 2 dispiro[oxindole-arylidene-cyclohexanone]pyrrolidines, 3 dispiro[oxindole-hexahydro-indazole]pyrrolidines, 3 and spiro[butenolide]pyrrolidines, 4 have been screened for their antibacterial and antifungal activity against ten human pathogenic bacteria and four dermatophytic fungi. They were found to have antimicrobial and antifungal activity compounds against various pathogens except Bacillus subtilis. The spiro pyrrolidinines were synthesized by the regioselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated either from isatin and sarcosine or from aziridine. The azomethine ylide so generated reacted with various dipolarophiles such as 2-arylidene-cyclohexanones, 2-arylidene-tetrahydronapthalen-1-ones, 2,6-bis(arylmethylidene)cyclohexanones and 3-arylidene-5-phenyl- butenolides.

Antifungal and Immunomodulating Activities of 1,4-Benzothiazine Azole Derivatives: Review

We reviewed the studies on the in vitro and in vivo antifungal activity of 1,4-benzothiazine azole derivatives (1,4-BT). A number of different 1,4-BT have been tested for anti-Candida activity, investigating their N-4 substitution, sulfur oxidation state, presence of the carbonyl group in C-3, insertion of the side chain on C-6, C-7 or C-8 of benzothiazine nucleus, the nature of azolic substituent (triazole or imidazole), which tend to differ. Moreover, benzoxazine analogues have been tested to evaluate the effect of sulfur bioisosteric substitution on their activity. We found that their antifungal activity correlates with well-defined chemical characteristics including the presence of ether substitution at the side chain. In fact, ether derivatives are the most active compounds in vivo, although they have little anti-Candida effect in vitro. This discrepancy could be attributed to the fact that 1,4-BT are metabolized to active antifungal compounds and may have in vivo activity through improvement of protective immune response and direct antifungal effects. In fact, 1,4-BT also show immunomodulating activity so that the direct antifungal activity, in combination with the capability to stimulate the immune response, could result in a significant increase in in vivo efficacy.

Study of the Cytotoxic and Antifungal Activities of Neolignans 8.O.4´ and Structurally Related Compounds

In the present work we report the antifungal and cytotoxic activities of a neolignan 8.O.4´series. The most active antifungal compounds show a significant cytotoxic effect which might be related.

ChemInform Abstract: Cell Wall Active Antifungal Compounds Produced by the Marine Fungus Hypoxylon oceanicum LL‐15G256. Part 2. Isolation and Structure Determination.

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Cell wall active antifungal compounds produced by the marine fungus hypoxylon oceanicum LL-15G256. I. Taxonomy and fermentation.

The cell wall targeted antifungal activity of Hypoxylon oceanicum LL-15G256 extracts resulted from the production of novel lipodepsipeptides and previously reported macrocyclic polylactones. In an optimized medium, titers of the lipodepsipeptide and the polylactones reached approximately 200-400 mg/liter and 25-50 mg/liter, respectively. The optimum fermentation temperature for production of 15G256 gamma was 28 degrees C. Seawater appeared to have an inhibitory effect on metabolite accumulation at lower fermentation temperatures.

Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. III. Biological properties of 15G256 gamma.

15G256 gamma is a cyclic lipopeptide antifungal agent discovered in a mechanism of action screen for cell wall acting antifungal agents. The compound shows moderate activity in both greenhouse tests against plant disease caused by pathogenic fungi and in in vitro tests against human fungal pathogens. Microscopic examination of treated fungi suggests that the compound acts by the inhibition of cell wall biosynthesis. However, in vitro inhibition of Neurospora crassa glucan and chitin synthase were only observed at high drug concentrations suggesting that 15G256 gamma may act on a novel cell wall target.

Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. II. Isolation and structure determination.

Fermentations of the marine fungus Hypoxylon oceanicum (LL-15G256) were found to have potent antifungal activity. Isolation and purification of the antifungal agents provided two classes of compounds, macrocyclic polylactones and the lipodepsipeptides 15G256 gamma (1), 15G256 delta (2) and 15G256 epsilon (3). The isolation and structure elucidation of the lipodepsipeptides, all containing D-glutamate, L-serine, and the rare amino acid beta-ketotryptohan, are described in this paper.

Antibacterial and Antifungal Properties of β-Naphthol Derivatives V

AbstractA detailed study was made on some derivatives of β-naphthol which have emerged as active antibacterial and antifungal compounds from a preliminary screening already reported. This included the evaluation of penetration power, influence of organic matter, and fungicidal activity. Further tests were carried out on a selected group of compounds, and covered such determinations as topical irritation and interference in the process of wound healing. The LD60 by intraperitoneal administration of 6-hexyl-j3-naphthoI was found to be 127 mg. per Kg. A potentiation of fungistatic action was observed with a few naphthol derivatives in formulations containing known anti-infective agents. All compounds seemed to possess good penetration power even in ointment vehicles and were nonirritant to the intact skin of rabbits. The presence of organic matter did not appear to curtail the activities of these compounds seriously and the compounds themselves did not seem to have any adverse effect on the process of wound healing. The results obtained from these limited tests indicated that the compounds may prove useful as anti-infective agents and hence seem worthy of further toxicity and clinical studies.