Marcos Derita

Value of the ethnomedical information for the discovery of plants with antifungal properties. A survey among seven Latin American countries.

ETHNOPHARMACOLOGICAL RELEVANCE This study reports the antifungal evaluation of 327 plant species (92 families and 251 genera) from seven Latin American countries which were selected on the basis of their reported ethnomedical uses and compared them with plants selected at random. AIM OF THE STUDY (a) The main aim of this study was to investigate whether the probability of detecting antifungal plants is higher when plants have reports of ethnopharmacological uses related to fungal infections (PAU group) than when they are selected at random (PNAU group). (b) The second objective was to determine, within the PAU group, whether the probability of obtaining a positive result will be higher when the plants are tested against dermatophytes, than against yeasts or Aspergillus spp. (c) The third goal was to investigate, within all MICs<or=1000 microg/mL, if the MICs displayed by the PAU group are comparatively lower than MIC values of the PNAU group; that is to say, if they can be expected more potent antifungal plants within the group of plants that have a history of traditional use related to fungal infections than when they do not have one. MATERIALS AND METHODS A five-stage process of documentation, evaluation and analysis of results was conducted: (1) selection of words that could describe the ethnopharmacological use related to fungal infections; (2) a survey of specialized literature in each country; (3) collection and preparation of an extract of each plant; (4) antifungal evaluation of the selected plants and (5) statistical analysis of the results. For the antifungal evaluation, the microbroth dilution assay recommended by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) was used against a panel of eleven human opportunistic and pathogenic fungi. For the statistical analysis the Pearsons Chi Square test and the Scores test were used. RESULTS (a) A significantly higher probability of detecting plants with antifungal activity against at least one fungus was found within the PAU (40.3%) than the PNAU group (21.3%) (p<0.01). (b) A similar higher probability than in (a) (39.6% vs. 20.8%) was found when plants were tested against dermatophytes (p<0.01) but not against yeasts or Aspergillus spp. (p>0.05). (c) Within the detected antifungal plants from both groups, plants of the PAU group displayed higher activities (lower MICs) than those of PNAU group against dermatophytes (p<0.05) but not against yeasts or Aspergillus spp. CONCLUSIONS Considering that dermatophytes are the cause of superficial fungal infections, which can be easily detected and followed by traditional healers, our findings suggest that the ethnopharmacological approach is useful in guiding the detection of antifungal plants in Latin America mainly for infections in which the pathological expression is obvious and, therefore, the cure can be clearly observed.

Relation between lipophilicity of alkyl gallates and antifungal activity against yeasts and filamentous fungi

The antifungal activity of a complete series of 15 n-alkyl gallates and six analogues acting against a representative panel of opportunistic pathogenic fungi was studied in order to analyze their role in: the importance of the fungi tested, the importance of the hydroxyls, the influence of the chain length and the hydrophobicity of the compounds. It was demonstrated that dermatophytes were the most susceptible species and that hydroxyls appear to be necessary but not sufficient for the activity. When the logP of each gallate was calculated and related to the different values of MIC against Microsporum gypseum it was observed that hexyl, heptyl, octyl and nonyl gallates exhibit a significant positive deviation from the curve corresponding to a polynomial equation obtained for the other gallates. This suggests that these compounds have a further mode of action besides their hydrophobicity, possibly the inhibition of some enzyme involved in ergosterol biosynthesis.

Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines

Diverse 2-pyridinyl quinolines 6-12 and 2-pyridinilvinyl quinolines 13-17 were prepared using a straightforward synthesis based on the BiCl(3)-catalyzed multicomponent imino Diels-Alder (imino DA) reaction or a novel tandem imino DA/catalytic tetrahydroquinoline ring oxidation/Perkin condensation sequential process. All members of the series showed activities against dermatophytes and some of them possessed a broad spectrum of action. 2-(Pyridin-4-yl)quinoline 9 and 2-(2-pyridin-4-yl)vinyl)quinoline 16 showed the best MIC(80) and MIC(50) against the clinically important fungi Candida albicans and non-albicans Candida species. In turn, 6-ethyl-2-(pyridin-2-yl)quinoline 6 showed the best properties against standardized as well as clinical strains of Cryptococcus neoformans.

Influence of plant part, season of collection and content of the main active constituent, on the antifungal properties of Polygonum acuminatum Kunth.

ETHNOPHARMACOLOGICAL RELEVANCE Polygonum acuminatum Kunth. (Polygonaceae) is used to heal infected wounds and as antifungal in the traditional Argentinean medicine. AIM OF THE STUDY The present investigation was carried out to evaluate the antifungal properties of aerial parts of Polygonum acuminatum, in order to give support to its ethnopharmacological use as antifungal agent and to isolate the compound(s) responsible for the antifungal properties. The influence of the plant part used, the season of the year and a study of the correlation of the antifungal activity with the content of the main active constituent were investigated too, with the aim of contributing to determine the most suitable plant extract and season of the year for achieving the best antifungal properties for Polygonum acuminatum traditional use. MATERIALS AND METHODS For the antifungal evaluation, the microbroth dilution assay recommended by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) was used against a panel of human opportunistic and pathogenic fungi. Bioassay-guided fractionation allowed us to isolate the compounds responsible for the antifungal activity. GC-MS was used to quantify the main component in the different extracts. For the statistical analysis, ANOVA test for analyses of variance followed by the Tukey test of Multiple Comparisons were used. The correlations between content of the antifungal compound and antifungal activity, were calculated with the Spearman Correlation Coefficient. RESULTS Aerial parts (A) of Polygonum acuminatum showed to possess antifungal properties against yeasts as well as dermatophytes but not against Aspergillus spp. From the most active extract (ADCM), polygodial, isopolygodial, drimenol and confertifolin were isolated, possessing polygodial a broader spectrum of action and lower MICs than the rest of compounds. Among the different parts, leaves (L), stems (S) and fruits (F), that constitute the aerial parts of Polygonum acuminatum, (L) showed to possess the best activities, compared to (S) and (F). The analysis of the content of polygodial in the LHex, LDCM, LEtOAC, LMeOH extracts collected in Summer, Autumn, Winter and Spring showed that LDCM of all seasons possessed higher percentages of this sesquiterpene than the rest of extracts. Among the LDCM of different seasons, that of Autumn was the most concentrated in polygodial. The correlation between content of polygodial with antifungal behavior of the different extracts, showed that LDCM of Autumn contains the highest content of polygodial and concomitantly the lowest MICs. CONCLUSION The ethnopharmacological use of Polygonum acuminatum aerial parts in the Argentinean traditional medicine for ailments related to fungal infections is supported by the results obtained in this investigation. From the obtained results, LDCM of Autumn, possessing the highest content of polygodial and the lowest MICs, appeared to be the most suitable extract for being used as antifungal in the traditional medicine. Nevertheless, if some other plant collection of another season different from Autumn is available, a LDCM extract would be the better option, because it contains a higher amount of polygodial compared to LHex, LEtOAc or LMeOH and therefore, a better antifungal activity can be expected.

Antifungal activity of Heterothalamus alienus metabolites

The chemical study of Heterothalamus alienus gave rutin, spathulenol (1), (1R,7S)‐germacra‐4(15),5,10(14)‐trien‐1β‐ol (2), sakuranetin (3), padmatin 3‐acetate (4), (2R,3R)‐dihydroquercetin‐7,3′,4′‐trimethyl ether (5), (2R,3R)‐dihydroquercetin‐7,4′‐dimethyl ether (6), (2R,3R)‐3‐acetoxy‐5,7,4′‐trihydroxyflavanone (7), as the main components of an antifungal extract of the aerial parts of the plant. Compound 2 showed moderate activity, with Epidermophyton floccosum being the most susceptible species (MIC = 100 µg/mL); compound 3 showed the best antifungal behavior having a broad spectrum of action and the lowest MICs. This flavanone along with flavanolol 5 showed very good activity against standardized (MIC = 31.2 µg/mL) as well as clinical isolates of Trichophyton rubrum and T. mentagrophytes (MIC ranges 31.2–62.5 µg/mL and 31.2–125 µg/mL, respectively) and demonstrated not only fungistatic but also fungicide properties. Flavanolol 6 was active against all the dermatophytes tested with MICs of 62.5–250 µg/mL. Rutin, spathulenol (1) and the 3‐acetylated flavanones 4 and 7 were inactive or marginally active against the fungal panel. Copyright

Synergistic antimicrobial potential of essential oils in combination with nanoparticles: Emerging trends and future perspectives

The development of resistance to different antimicrobial agents by bacteria, fungi, viruses, parasites, etc. is a great challenge to the medical field for the treatment of infections caused by them, and therefore, there is a pressing need to search for new and novel antimicrobials. The antimicrobial activity of essential oils and biogenic nanoparticles is well known. Recent studies have demonstrated that nanoparticles functionalized with essential oils have significant antimicrobial potential against multidrug- resistant pathogens. The aim of the present review is to discuss various studies on the broad-spectrum antimicrobial activity of essential oils used singly and in combination with nanoparticles. The brief explanation of their mechanism has also been discussed.

Synthesis of steroidal quinones and hydroquinones from bile acids by Barton radical decarboxylation and benzoquinone addition. Studies on their cytotoxic and antifungal activities.

Twelve new hydroquinones and quinones (4a-c to 7a-c) derived from free or peracetylated bile acids were prepared by a Barton decarboxylation reaction, with subsequent trapping of the resulting free radical by benzoquinone. All new compounds were completely characterized by 2D NMR techniques and screened for antifungal and cytotoxic activity. One of the new hydroquinones (7b) showed promising results against the human pancreatic ductal carcinoma cell line PANC1, with similar cytotoxic activity as the commercial chemotherapy drug doxorubicin.

CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY OF ESSENTIAL OIL FROM BACCHARIS GRISEBACHII HIERON (ASTERACEAE)

The essential oil of the aerial parts of Baccharis grisebachii was examined by GC and GC-MS and evaluated for its antimicrobial properties. Forty three essential oil constituents were identified representing 94.3% of the total. Thymol, thymol methyl ether, thymyl acetate, alpha pinene, alpha humulene, and globulol were found to be the major components. The oil showed MIC values < 250 μg/mL against Cryptococcus neoformans (125 μg/mL), Aspergillus spp. (125 μg/mL), and particulary against Trichophyton mentagrophytes and T. rubrum (62.5 μg/mL)

Structural Requirements for the Antifungal Activities of Natural Drimane Sesquiterpenes and Analogues, Supported by Conformational and Electronic Studies

Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5–17 obtained from 1–3, were evaluated in vitro for antifungal properties against a unique panel of fungi with standardized procedures by using two end-points, MIC100 and MIC50. A SAR analysis of the whole series, supported by conformational and electronic studies, allowed us to show that the Δ7,8 -double bond would be one of the key structural features related to the antifungal activity. The MEPs obtained for active compounds exhibit a clear negative minimum value (deep red zone) in the vicinity of the Δ7,8 -double bond, which is not present in the inactive ones. Apart of this negative zone, a positive region (deep blue) appears in 1, which is not observed either in its epimer 2 nor in the rest of the active compounds. The LogP of active compounds varies between 2.33 and 3.84, but differences in MICs are not correlated with concomitant variations in LogP values.

Synthesis, Bioevaluation and Structural Study of Substituted Phthalazin-1(2H)-ones Acting as Antifungal Agents

Twenty-five polysubstituted phthalazinone derivatives were synthesized and tested for their antifungal activity against a panel of pathogenic and clinically important yeasts and filamentous fungi. Among them, the compound 4-(4-chlorobenzyl)-2-methylphthalazin-1(2H)-one (5) exhibited a remarkable antifungal activity against standardised strains of dermatophytes and Cryptococcus neoformans, as well as against some clinical isolates. A physicochemical study performed on compound 5 revealed its conformational and electronic characteristics, providing us with useful data for the future design of novel related antifungal analogues.