Antifungal activity of Aegle marmelos(L.) Correa(Rutaceae) leaf extract on dermatophytes

Objective:To evaluate the in vitro antifungal activity of Aegle marmelos leaf extracts and fractions on the clinical isolates of dermatophytic fungi like Trichophyton mentagrophytes,Trichophyton rubrum,Microsporum canis,Microsporum gypseum and Epidermophyton floccosum.Methods:The minimum inhibitory concentration(MIC) and minimum fungicidal concentration(MFC) of various extracts and fractions of the leaves of Aegle marmelos were measured using method of National Committee for Clinical Laboratory Standards(NCCLS).Results:Aegle marmelos leaf extracts and fractions were found to have fungicidal activity against various clinical isolates of dermatophytic fungi.The MIC and MFC was found to be high in water and ethyl alcohol extracts and methanol fractions(200μg/mL) against dermatophytic fungi studied.Conclusions:Aegle marmelos leaf extracts significantly inhibites the growth of all dermatophytic fungi studied.If this activity is confirmed by in vivo studies and if the compound is isolated and identified,it could be a remedy for dermatophytosis.

Dermatophytes Species Isolated of HIV-Infected Patients Identified by ITS-RFLP and ITS Region Sequencing from Triangulo Mineiro, Minas Gerais State of Brazil

Dermatomycoses are a group of diseases worldwide distributed and affect skin, hair and nails. Several fungal species can be envolved and keratinophilic fungi belonging to the genera Trichophyton, Microsporum and Epidermophyton are very common. These infections are globally distributed and their incidence has progressively increased. Despite their high incidence, few studies have been carried out in HIV-infected patients, regarding frequency, clinical presentations, and species identification. This study aimed to evaluate some epidemiological and clinical aspects of dermatophytosis in HIV-infected patients and to attempt phenotypical and molecular characteristics of their agents. Of 398 patients included, 306 were HIV-infected. Clinical data and samples of skin, hair and nail lesions were simultaneously obtained. The dermatophytes yielded in culture were phenotypically identified and evaluated by ITS-RFLP and ITS (Internal Transcribed Space) sequencing. Dermatophytes frequency in HIV-infected patients with cutaneous lesions was 11.76% similar to the 15.22% observed in non-HIV individuals. Trichophyton rubrum was the most common isolated species in both groups. Throught ITS-RFLP, 29/32 (90.63%) of dermatophytes isolates were identified at the species level. From the 10 isolates randomly selected for ITS sequencing, seven confirmed the ITS-RFLP results while three Trichophyton sp. were not identified as dermatophytes. The identification of these species in HIV-infected patients is highly desirable in order to improve the knowledge of their frequency, geographical distribution and relation to clinical presentation.

Distribution and Prevalence of Dermatophytes in Semi-Arid Region of India

Earth has been documented as a natural territory for fungi which cover individual kingdom with evolution. In subsequently vertebrates developed keratin which was a part of life as a structural aspect. Few moulds have skilled to digest keratin and crop up from soil and wastewater habitats. They take part as a keratinolytic agent in the purification of α-keratins with an incidence of disulphide and hydrogen bonds which are improperly biodegradable. The best moulds genera to decay of keratin are Microsporum, Trichophyton and Epidermophyton. The presences of these genera are open health issues in developing countries where they cause the mortal mycotic contagion. The reason behind this is perceived to be the poor hygienic environment and socioeconomic behaviour among people. The present review is a compilation of updated information concerning the nature of these keratinolytic moulds and abundances of most contributed developing countries including India.

Pattern of Dermatophytes Isolated in the Medical Microbiology Laboratory of the University of Port Harcourt Teaching Hospital, Rivers State, Nigeria

Dermatophytoses are the most common dermatological conditions but they are however not life threatening or debilitating hence medical care is sought usually due to aesthetic reasons and chronicity of the lesions despite several self-medications. The purpose of this study was to determine the distribution pattern of dermatophytes isolated in the medical microbiology laboratory of University of Port Harcourt teaching hospital (UPTH). This is a 5-year desk review of the Dermatophytes isolated in the medical microbiology laboratory of UPTH. Relevant Patients’ data were retrieved and analyzed. A total of seventy (70) dermatophytes were isolated over the five-year period as follows: Trichophyton species accounted for 55 (79%), Epidermophyton species were 8 (11%) and Microsporum species 7 (10%). The peak age range of patients from which dermatophytes were isolated was 31 - 40 years with a male to female ratio of 1:1.7. The majority of patients being 49 (70%) were referred from the dermatology outpatient clinic (DOPC) and the most frequent clinical diagnosis was Tinea corporis. Trichophyton species were the commonest cause of dermatophytoses in adult patients in Port Harcourt where the most common clinical presentation was Tinea corporis.

<i>In Vitro</i>Susceptibility of Dermatophytes to Anti-Fungal Drugs and Aqueous <i>Acacia nilotica</i>Leaf Extract in Lagos, Nigeria

Dermatophytes were earlier reported to respond well to anti-fungal agents;however, an upsurge in resistance with the high cost of these agents increased the use of medicinal plants for treatment. This study investigated the sensitivity pattern of dermatophytes to oral anti-fungal drugs and aqueous leaf extract of the plant, Acacia nilotica. The extract was tested against seven strains of dermatophytes Arthroderma otae, Trichophyton interdigitale, Trichophyton mentagrophyte, Microsporum ferrugineum, Arthroderma vespertilii, Arthroderma quadrifidum, and Arthroderma multifidum, previously isolated from diabetic patients. The minimum inhibitory and fungicidal concentrations of the plant extracts and the standard antifungal agents were evaluated using modifications of the broth macro dilution method of the National Committee for Clinical Laboratory Standards M38-A2 protocol. There was a significant difference in the Minimum Inhibitory concentrations (MIC) of the dermatophytes to the three antifungal drugs tested (p < 0.001). The dermatophytes were mostly susceptible to itraconazole followed by Nystatin. All the dermatophytes tested were resistant to griseofulvin. Acacia nilotica had an inhibitory effect on all the dermatophytes tested, and showed anti-fungal activity in a dose-dependent relationship between 0.625 - 1.25 mg/ml. Though the inhibitions of the dermatophytes were significantly higher with the standard anti-fungal drugs as compared to the plant extract (p < 0.001);however, the dermatophyte, Arthroderma quadrifidum, which was resistant to all the anti-fungal drugs, had the highest inhibition with A. nilotica. Some circulating dermatophyte strains in Nigeria are griseofulvin and/or itraconazole resistant which may influence the spread of infection and A. nilotica aqueous leaf extract showed a strong anti-dermatophytic activity.

Morphological and Molecular Identification of Two Strains of Dermatophytes

In this study, we used traditional morphological and molecular identification methods to preliminarily identify two strains of dermatophytes. The two strains were observed under the micro- scope. And then the dermatophytes were cultured on Sabouraud＇s dextrose agar （SDA）. The 18S rRNA regions of the two dermatophyte strains were amplified by polymerase chain reaction （PCR）, and the PCR products were sequenced and compared with GenBank data. BLAST tools and DNAMAN soft- ware were used to analyze the sequences. To further determine highly homologous sequences, a phy- logenetic tree was constructed using the Neighbor-Joining method. The two strains of dermatophytes were identified by traditional morphological identification as Epidermophyton floccosurn and Micro- sporum ferrugineum. The 18S rRNA sequence analyses showed high similarities to Cladosporium cladosporioides isolate Cll5LM-UFPR and Ascomycete sp. LB68A1A2. Epidermophyton and Cladosporium belong to dermatophyte, while Microsporum ferrugineum and Ascomycete belong to mi- crosporum. The two novel strains of dermatophytes were therefore identified as Cladosporium cladosporioides isolate C115LM-UFPR （JN650537, Cladosporium ） and Ascomycete sp. LB68A1A2 （AY770409, Ascomycete sp）.

Clinical Identification of Common Species of Dermatophytes by PCR and PCR-RFLP

Summary: To find a fast and efficient way of identifying seven common dermatophytes in clinical practice, we used the techniques of polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) targeting TopoisomeraseⅡgene. The DNA of 7 dermatophytes, along with Candida albicans, Aspergillus terreus and Aspergillus flavus were amplified by consensus primer dPsD1. They were then subjected to a second PCR with primers dPsD2 and species-specific primers PsT and PsME separately. 6 of the products generated by dPsD2 were digested with restriction enzyme HincⅡ. DNA fragments of 3390 bp and 2380 bp was amplified by using consensus primer dPsD1 and dPsD2 from the genomic DNA of each dermatophyte species separately. By combining the results of the two species-specific primer sets (PsT and PsME), all species of dermatophyte yielded unique sizes-set of PCR products expect for T. mentagrophytes and T. tonsurans. From the restriction profiles of HincⅡ, 6 of the 7 dermatophytoses were diagnosed to species level including T. mentagrophytes and T. tonsurans. By combining the results of the PCR and PCR-RFLP, the 7 common dermatophytes can be identified to species level. It is conclude that the multiplex PCR and PCR-RFLP identification targeting the DNA topoisomerase Ⅱ gene is rapid and efficient.

Identification of Common Species of Dermatophytes by PCR-RFLP

To establish a simple, sensitive and effective technique for the identification of six common dermatopbytes, polymerase chain reaction （PCR） and PCR-restriction fragment length polymorpbism （RFLP） targeting Topoisomerase Ⅱ gene were used. The DNA of 6 common dermatopbytes was amplified by primer dPsD1 and then primers dPsD2. The products generated by dPsD2 were digested with restriction enzyme Hinc Ⅱ and Hinf Ⅰ separately. A DNA fragment of about 3390 bp was amplified by using primer dPsD1 from the genomic DNA of each dermatopbyte species. The product of dPsD2 was 2380 bp and the restriction profiles of Hinc Ⅱ and Hinf Ⅰ were between 58-1670 bp. By using PCR-RFLP, all of the 6 dermatopbytoses were diagnosed to species level and no obvious difference identification between Hinc Ⅱ and Hinf Ⅰ. It is concluded that the PCR-RFLP identification of dermatopbytes by Hinc Ⅱ or Hinf Ⅰ is efficient and rapid in clinical practice.

Antifungal Susceptibility Testing of Dermatophytes by ABDD and E-Test, a Comparative Study

Aim: The objective of this study was to isolate, identify, and explore the in-vitro antifungal susceptibility pattern of dermatophytes isolated from clinically suspected cases of dermatophytosis (tinea infections) attending the Dermatology Department at J.S.S Hospital. Methods: This study was conducted at JSS Medical College and Hospital from December 2016 to December 2017. Clinical samples (e.g., skin scrapings and hair stumps) were collected under aseptic precautions. The identification of dermatophytes was performed through microscopic examination using 10%, 20% & 40% potassium hydroxide (KOH) and culture on Sabouraud dextrose agar (SDA), SDAac, PDA and Dermatophyte test medium (DTM). All dermatophytes isolates were subjected to antifungal susceptibility testing using the agar-based disk diffusion (ABDD) and E-test method against Terbinafine, Itraconazole, Fluconazole, and Griseofulvin. Data were analyzed by using Chi square test. Results: A 100 samples were studied, 46% tinea corporis, 2%tinea cruris, 9% tinea pedis, 5% tinea faciei. The dermatophytes isolated were Trichophyton rubrum 11 (35%), Trichophyton mentagrophyte 8 (25%), Trichophyton tonsurans 5 (16%), Microsporum gypseum 3 (10%), Trichophyton verrucosum 2 (6%), Trichophyton violaceum 1 (3%) and Microsporum audouinii 1 (3%). Out of 31 dermatophytes 17 were sensitive to all four antifungal agents within the range of FLC (2 - 6 mcg/ml), ITR (0.125 - 2), TER (0.125 - 2), and GRI (0.125 - 2), 5 isolates were resistant in which 2 were resistant to FLC (64.256 mcg/ml), 2 isolates were resistant to TER 2 (32.38 mcg/ml), 1 isolate was resistant to both GRI and TER (16.32 mcg/ml) and 9 isolates were within the intermediate range. Conclusion: Every patient with a tinea infection should be properly studied for a mycological examination and should be treated accordingly. Dermatophyte test medium is more useful as an identification medium in the isolation of dermatophytes. The ABDD method appears to be a simple, cost-effective, and promising method for the evaluation of antifungal susceptibility of dermatophytes. E-test method is the most sensitive method due to the fact that quantitative MICs can be obtained directly from the E-strip. However, the E-test method is expensive and difficult in defining the precise borders of the inhibition zones in dermatophytes.

The homology analysis of internal transcribed spacer sequence of ribosomal DNA in common dermatophytes

In order to analyze the sequences of the internal transcribed spacer （ITS） including the 5.8 S ribosomal DNA （rDNA） of common dermatophytes, so as to obtain a rapid and accurate method to identify the species of dermatophytes and to establish the phylogenetic tree of these species to understand their relationship, 16 strains of dermatophytes were collected and preliminarily identified by morphological characteristics. General primers for fungi ITS1 and ITS4 were used to amplify the ITS rDNA of each strains with PCR. The PCR products after purification were sequenced directly and were analyzed through internet. In the results, 11 strains were identified by means of morphological features, among which 5 strains were Trichophyton, 5 strains were Microsporum and 1 was Epidermophytoa, which was consistent with the results by molecular biology. In the 5 unidentifiable strains, 1 strain was proved to be Chrysosporium by molecular biology. These strains studied could be divided into 3 different classes as indicated in the analysis of the phylogenetic tree of the sequences in ITS, which were quite different from those of morphological classification. It is evident from the above observations that the molecular method of analysis on the ITS sequences is a rapid, highly sensitive and accurate approach for the detection of dematophyte species, however, it still exhibits some limitations needing the supplementation with morphological identification.

Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function

Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties.Despite its widespread use,scientific evidence validating the antifungal efficacy of A.argyi water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains limited.This study aimed to substantiate the scientific basis of the folkloric use of A.argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes.The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species.The subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent subfraction.The minimum inhibitory concentrations(MICs)of AAWE6 against T.rubrum,M.gypseum,and T.mentagrophytes were 312.5,312.5,and 625μg·mL−1,respectively.Transmission electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T.rubrum,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy metabolism.Additionally,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of AAWE6.In conclusion,the subfraction AAWE6 from A.argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function.This research validates the traditional use of A.argyi and provides scientific support for its antidermatophytic applications,as recognized in the Chinese patent(No.ZL202111161301.9).

Antimycotic efficacy of Iranian medicinal plants towards dermatophytes obtained from patients with dermatophytosis

从 Artemisia sieberi， Cuminum cyminum， Foeniculum vulgare， Heracleum persicum， Menta spicata， Nigella sativa， Rosmarinus officinalis， Zataria multiflora 和 Ziziphora 瞄准九植物香精油(曙光女神) ，包括那些 clinopodioides，为他们的 anti-dermatophytic 性质被评估。测试皮藓菌包括了 Trichophyton mentagrophytes (号码 32 ) 的方法， T。rubrum (号码 29 ) ， Epidermophyton floccosum (号码 19 ) ， Microsporum gypseum (号码 11 ) 和 M。canis (号码 42 ) 。植物油的危险性测试被由临床的实验室标准协会描述了的肉汤 microdilution 技术以最小的禁止的集中(MIC ) 和最小的杀菌剂集中(MFC ) 执行。所有曙光女神学习了的结果对皮藓菌是活跃的。MIC 为测试的植物油记录了从 0.25 ～ 4 mg ‰ ? 娠潨杮潺杮?? € 楑 ???????????? 丠??? ? ㈠吗？？

特比萘芬对皮肤癣菌形态学的影响

目的观察皮肤癣菌在特比萘芬作用下形态学变化。方法应用美国CLSI制订的标准M38-A方案进行特比萘芬对皮肤癣菌的体外药敏试验,测定MIC值,将特比萘芬作用前后的皮肤癣菌制成标本,分别在光学显微镜、扫描电子显微镜和透射电子显微镜下观察形态学变化。结果特比萘芬作用于皮肤癣菌后,在光学显微镜下菌丝变的弯曲、短粗,顶端和局部出现膨大。扫描电子显微镜下菌丝变的弯曲、短粗、干瘪,顶端和局部出现膨大,有不规则分枝,表面粗糙,有大小不等的凹陷。透射电子显微镜下菌丝变得皱缩,有凹陷,双层细胞壁结构消失和不完整,细胞膜不连续,皱缩细胞膜和细胞壁之间及胞浆内出现许多小的高电子密度颗粒,细胞器也变得不清晰。结论特比萘芬使皮肤癣菌的形态发生明显变化。

Extracts of the seaweed Bifurcaria bifurcata display antifungal activity against human dermatophyte fungi

Bifurcaria bifurcata is a seaweed of the Order Fucales(Ochrophyta,Phaeophyceae)that can be found all year round along the Portuguese Atlantic shore.Although it is considered edible in some countries,its biotechnological potential has not yet been assessed in detail and here we report its antimicrobial potential against human dermatophyte fungi.Three samples were harvested from Baleal Island(Peniche,Portugal)harvested in winter(BbPe);from Aguda Beach(Arcozelo,Vila Nova de Gaia,Portugal),harvested in autumn(BbAg)and a sample obtained by culturing the Aguda sample under laboratory conditions(BbLC).A broth macrodilution assay was applied to determine the MIC(minimum inhibitory concentration)and MLC(minimum lethal concentration)of the B.bifurcata extracts.Results show that the BbPe MeOH extracts were the most effective and had higher antifungal activity against all the tested dermatophyte strains than the BbLC and BaAg extracts[Epidermophyton floccosum FF9(100–200μg/mL MIC;200μg/mL MLC),Microsporum canis FF1(400μg/mL MIC;≥400μg/mL MLC),Trichophyton mentagrophytes FF7(100μg/mL MIC;>800μg/mL MLC),M.gypseum CECT 2908(800μg/mL MIC;≥800μg/mL MLC),T.mentagrophytes var.interdigitale CECT 2958(800μg/mL MIC;≥800μg/mL MLC),T.rubrum CECT 2794(200μg/mL MIC;≥400μg/mL MLC)].In fact,only E.floccosum FF9 was sensitive to BbAg and BbLC MeOH extracts.To our knowledge,this is the first report of antifungal activity of B.bifurcata against human dermatophyte fungi.

Therapeutic Effects of Essential Oil from Waste Leaves of <i>Psidium guajava</i>L. against Cosmetic Embarrassment Using Phylogenetic Approach

Medicinal plants are facing threats due to loss of habitat and overexploitation of knows species. Therefore the present work shows utilization of essential oil from discarded leaves of Psidium guajava Linn. against human dermatophytic fungi Trichophyton rubrum, T. mentagrophytes, Trichophyton violaceum, Trichophyton tonsurans, Epidermophyton floccosum, Microsporum gypseum and Microsporum canis. The oil was found to be fungicidal at 3.0 μl/ml and it tolerated heavy inoculum of pathogens at fungicidal concentrations. The fungicidal activity of the oil was thermostable, up to 70°C and shelf life was found to be six months, which was maximum the time taken into consideration. The oil having cineole, caryophyllane, copaene, azulene and eucalyptol as main constituents, exhibited broad fungicidal activity. The oil did not show any adverse effect on mammalian skin upto 5% concentration. Phylogeny of the dermatophytes with respect to toxicity of the oil has also been discussed using molecular data. The cost effective formulation from waste leaves can be exploited after undergoing double blind successful multicentral topical testing.

Laboratory Limits on Dermatophyte Diagnosis in Rabbits with Clinical Lesions

Dermatophyte infection or ringworm is a superficial cutaneous infection with one or more of the fungal species of the keratinophilic genera Microsporum, Trichophyton, or Epidermophyton and is a zoonosis with a great impact on public health. Dermatophytes were identified from rabbit sample cultures submitted to mycological examination in the Laboratory of Microbiology of the University of Tr^-os-Montes e Alto Douro, Vila Real, Portugal. All samples were collected from suspected clinical cases. Dermatophytes were cultured from 4 of the 55 specimens （7.3%）. The dermatophytes isolated were Trichophyton mentagrophytes var. mentagrophytes （1.8%） and Microsporum gypseum （5.5%）. Microscopic examination was negative in all specimens. In this work, Scopulariopsis spp., a contaminant mould, was identified in 13 specimens （23.6%）. The proportion of positive samples in relation to the number of samples examined from cases suspected was very low. As all samples were collected from rabbits with compatible signs, we presume that the low prevalence of isolation was due to laboratory constraints on dermatophytes diagnosis.

Inflammatory Tinea Manuum due to <i>Trichophyton erinacei</i>from an African Hedgehog

The zoophylic dermatophytes, as Trichophyton erinacei, frequently cause very inflammatory tineas in the human host. This dermatophyte is carried by some pets, particularly by the terrestrial hedgehog. Herein, we present the case of a 22-year-old male student with an exudative erythematous scaly plaque on his right fifth finger for 1 month. He had a pet African hedgehog (Atelerix albiventris). KOH examination demonstrated hyphae compatible with dermatophytes. The culture revealed a white, radiated dusty colony. PCR sequencing of the region ITS1-5.8S-ITS2 identified T. erinacei. The final diagnosis was inflammatory tinea manuum due to T. erinacei. Clinical and mycological cure was achieved after treatment with oral terbinafine 250 mg/day × 1 month.

Anti-fungal potency of some Unani drugs in the treatment of dermatophytoses(Qūba)

Qūba(dermatophytoses)is a clinical condition caused by fungal infection of skin in humans.The fungi that cause dermatophytoses feed on keratin,the material found in the outer layer of skin,hair and nails.Many effective synthetic antifungal drugs have been discovered for the treatment of dermatomycoses but their use has remained limited due to various side effects on human systems.Herbal remedies are being used for its treatment.Unani medicines are also being promoted as dermatophytoses treatment.Detailed management consisting of single herbs and compound formulations along with other regimes has been mentioned to treat this disease in the classical Unani literature,which is safe and effective.The aim of this study was to systematically review the evidence for this notion and to discuss different aspects of Qūba(dermatophytoses).Extensive literature searches were carried out to identify drugs reported to be effective in the treatment of Qūba(dermatophytoses).In this review paper author has tried to present few Unani medicines prevalently used for treatment of dermatophytoses.

Mycotic Infections in Diabetic Patients in Casablanca

Introduction: The diabetes constitutes the factor risk of mycotic infections. The pathogenic agents depend on the climate, geography and the migration. The objective of this study is to evaluate the prevalence of the mycotic infections within the hospitalized diabetic patients, to describe their localization and identify the responsible germs. Patients and methods: It is about a descriptive and retrospective study conducted from November 2015 to March 2016 in endocrinology office at CHU Ibn Roch of Casablanca. It was included all diabetic patients hospitalized with whom mycotic infection has been suspected. Results: In total 350 diabetic patients have been hospitalized during the period of research. A mycotic infection has been suspected in 138 patients corresponding to the prevalence of 39.4 percent. The means localizations of mycotic infections were feet (intertrigos: 38.4%), onychomycosis (29%), vulvovaginal (21.7%) and mouth (oral candidiasis: 13.3%). The most frequent pathogenic agents were dermatophytes (Trichophyton rubrum: 61%, Trichophyton mentagrophytes: 6.3%) and Candida albicans (23.1%). The direct test and the culture were negative in 7.3%. Conclusion: One-third of the diabetic patients showed a mycotic infection. The feet, constitute the predilection localization of mycotic infections in the diabetic. The dermatophytes and Candida albicans constitute the most frequent pathogenic agents found in our study.

Antifungal Activity and Toxicity of the 3,4,5-Trihydroxybenzoic and 3,4,5-Tris(Acetyloxy)Benzoic Acids

Invasive fungal infections have been gaining notoriety due to several factors, mainly their increasing incidence in immunocompromised patients. The aim of the present study was to evaluate the antifungal activity and toxicity of the 3,4,5-trihydroxybenzoic acid (3,4,5-THB) and of its derivative, the 3,4,5-tris(acetyloxy)benzoic acid (3,4,5-TAB). The 3,4,5-THB was purchased and its derivative was obtained by purifying and characterizing performed using semisynthesis reactions (esterification), recrystallization, column chromatography and infrared analytical techniques and nuclear magnetic resonance. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were determined in order to evaluate the antifungal activity of the compounds against four clinical isolates and four standard strains of Candida sp. and five clinical isolates of dermatophytes, following the Clinical and Laboratory Standards Institute protocols. The toxicity of the compounds was evaluated by determining the lethal dosis (LD50) using lethality assay of Artemia salina. The most sensitive yeasts to the 3,4,5-THB were C. albicans ATCC 10231 and C. krusei ATCC 6258, both presenting a MIC of 128 μg·mL-1. For Trichophyton sp. and Epidermophyton floccosum, the MIC was 32 μg·mL-1. The 3,4,5-TAB showed a lower inhibitory activity against Candida and dermatophyte species tested. The LD50 of 3,4,5-THB was 222.60 μg·mL-1 and the 3,4,5-TAB showed 481.69 μg·mL-1 of LD50. In conclusion, the 3,4,5-trihydroxybenzoic acid showed antifungal activity against species of medical importance, mainly dermatophytosis-causing fungi, and the 3,4,5-tris(acetyloxy)benzoic acid showed no increasing antifungal activity and toxicity in relation to the original compound.