Assessing the Efficacy of Lemongrass (Cymbopogon citratus) and Sambong (Blumea balsamifera) Extracts in Combating Black Pod Disease: Sustainable Solutions for Controlling Phytophthora megakarya in Cameroon’s Cocoa Plantations

The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effective. This study evaluated the effectiveness of Cymbopogon citratus and Blumea balsamifora leaf extracts, both individually and in combination, against Phytophthora megakarya. We assessed the efficacy of the most promising combination (75% B. balsamifera, 25% C. citratus) after storage at room temperature for up to 9 days. Agar microdilution and in vivo bioassays were conducted to determine antifungal susceptibility and effectiveness. Blumea extract exhibited the highest overall inhibitory activity, with the lowest minimum inhibitory concentration (117 µl mL−1) while C. citratus had a narrower range of MIC (146 to 233 µl mL−1). The combination of C. citratus and B. balsamifera demonstrated a synergistic effect against P. megakarya, achieving growth inhibition on V8 media (92.72 ± 4.20% to 100%) and on artificially infected detached pod cortex (92.24 ± 4.53% to 98.75 ± 1.25%), which was not significantly different from the positive control (Ridomil). Furthermore, this combination maintained its effectiveness for up to 9 days at room temperature. These findings suggest that combining plant extracts can enhance their antifungal properties.

Synthesis of Pyridazinonethiadiazoles as Possible Antifungal Agents

Several 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl]-2-arylamino-1,3,4-thia diazoles were synthesized. The preliminary bio-active test shows that these compounds exhibit high antifungal activity.

Synthesis of a New Series of Chalcone Derivatives and Their Antifungal Activities

To study the antifungal effect of chalcone derivatives. Methods Sixteenchalcone derivatives were synthesized and confirmed by ~1H NMR and IR spectra, and tested forantifungal activity against four common pathogenic fungi. Their structure-activity relationship isdiscussed. Results Among 16 title compounds, there were 5 new compounds, which have not beenreported before. The preliminary antifungal test showed that all title compounds exhibitedantifungal activities to a certain extent. The activity of compound 8 against Trichophyton rubrumhad a potency equal to that of fluconazole, with a MIC of 4 μg·mL^(-1) . Conclusion Sixteenchalcones were prepared and their antifungal activities against four common pathogenic fungi invitro were examined. Some of them exhibited antifungal activities to a certain extent.

Value of eosinophil count in bronchoalveolar lavage fluid for diagnosis of allergic bronchopulmonary aspergillosis: A case report

BACKGROUND An immediate hypersensitive immune response to Aspergillus fumigatus antigens is one of the main characteristic features of allergic bronchopulmonary aspergillosis(ABPA).As ABPA is an allergic respiratory disease,immunoglobulin E and peripheral-blood eosinophilia have been used as diagnostic indicators.However,eosinophilia in bronchoalveolar lavage fluid(BALF)has not been considered in the diagnostic criteria for ABPA.CASE SUMMARY We present a case of ABPA in which the eosinophil count in peripheral blood was not increased,whereas the eosinophil percentage in BALF reached 60%.After antifungal and hormone therapy,imaging revealed very good resolution of lung infiltration.CONCLUSION The value of the eosinophil count in BALF for the diagnosis of ABPA is worthy of the clinician's attention,especially when the patient’s clinical features lack specificity and the diagnostic parameters are negative.

Topical Treatment of Infectious Vaginitis:Effects of Antibiotic,Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains

Objectives: The balance of the vaginal ecosystem depends on lactobacilli whose biofilm protectsagainst microorganisms that are not normally present or are subdominant in vaginal flora. Vaginal?infection treatments should eliminate pathogens while preserving the?Lactobacillus?flora to prevent relapse or recurrence. The objective of this study was to determine the sensitivity of lactobacilli to antiseptics, antibiotics and antifungal agents used, alone or in combination, in the topical treatment of infectious vaginitis. Materials and Methods: The minimum inhibitory concentration (MIC) of 15 active ingredients and the minimum inhibitory dilution (MID) of 17 pharmaceuticals products were determined for three main?Lactobacillus?strains (L. crispatus,?L. gasseri?and?L. jensenii). Results: The MICs of the antibiotics and antifungal agents were above their critical concentrations in the three strains, contrary to the antiseptics. According to their MID, some pharmaceutical products, especially combinations, inhibit the growth of one or more strains at concentrations that can be found in the vaginal mucosa after application at the usual dosage. Conclusions: Certain topical anti-infective drugs may interfere with the growth of lactobacilli, worsening the vaginal flora imbalance. Maintaining vaginal flora balance should be a selection criterion when choosing an anti-infective therapy.

Identification of a Candida albicans Biofilm Inhibitor

Candida albicans proliferates in the skin and oral cavity and is the causative agent of candida dermatitis and oral candidiasis. C. albicans is known to form biofilms on oral mucosa and denture surfaces. Formation of biofilms deteriorates the permeability of antifungal drugs, decreasing their effectiveness. Therefore, in this study, I identified a compound with inhibitory activity against C. albicans biofilm formation. Heat shock protein 90 was selected as the target protein, and a potential ligand for the same was extracted and identified as 2-(4-methylpiperazin-1-yl)cyclopentanol. C. albicans was then cultured with varying concentrations of this compound: 0 mmol/L, 0.63 mmol/l. 2.5 mmol/l, and 10 mmol/l, and biofilm formation was measured via crystal violet assay. The findings demonstrated that 2-(4-methylpiperazin-1-yl)cyclopentanol substantially inhibits biofilm formation when added at a concentration of 0.63 mmol/l or higher. It is suggested that C. albicans could be eliminated more efficiently using this compound in combination with the existing antifungal drug miconazole. Further, the compound may also be useful as a disinfectant for medical devices, such as catheters, to prevent the formation of C. albicans biofilms.

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.

Polygalacturonase-inhibiting proteins as an exogenously applied natural solution for prevention of postharvest fungal infections

Polygalacturonase inhibiting proteins(PGIPs)are plant proteins involved in the inhibition of polygalacturonases(PGs),cell-wall degrading enzymes often secreted by phytopathogenic fungi.Previously,we confirmed that PGIP2 from Phaseolus vulgaris(PvPGIP2)can inhibit the growth of Aspergillus niger and Botrytis cinerea on agar plate.In this study,we further validated the feasibility of using PGIP as an environmental and ecological friendly agent to prevent fungal infection post-harvest.We found that application of either purified PGIP(full length PvPGIP2 or truncated tPvPGIP2_5-8),or PGIP-secreting Saccharomyces cerevisiae strains can effectively inhibit fungal growth and necrotic lesions on tobacco leaf.We also examined the effective amount and thermostability of PGIP when applied on plants.A concentration of 0.75 mg/mL or higher can significantly reduce the area of B.cinerea lesions.The activity of full-length PvPGIPs is not affected after incubation at various temperatures ranging from20 to 42◦C for 24 h,while truncated tPvPGIP2_5-8 lost some efficacy after incubation at 42◦C.Furthermore,we have also examined the efficacy of PGIP on tomato fruit.When the purified PvPGIP2 proteins were applied to tomato fruit inoculated with B.cinerea at a concentration of roughly 1.0 mg/mL,disease inci-dence and area of disease had reduced by more than half compared to the controls without PGIP treatment.This study explores the potential of PGIPs as exogenously applied,eco-friendly fungal control agents on fruit and vegetables post-harvest.

Graphene oxide-Fe_3O_4 nanocomposites as high-performance antifungal agents against Plasmopara viticola

Plasmopam viticola, a causal agent of grapevine downy mildew, is a widely distributed pathogen, which can cause destructive disease in field-grown grapevines. Although fungicides are used to treat the disease, fungicide-resistant strains have been emerging. In this study, we developed graphene oxide （GO）-Fe3O4 nanocomposites, which could effectively repress the germination of sporangia and inhibit the development of downy mildew. 50 μg mL^-1 GO-Fe3O4 showed excellent protective and fungiddal activities. 250 μg mL^-1 GO-Fe3O4 on grapevine leaves in the field could significantly decrease the severity of downy mildew, suggesting its potent curative effect. Moreover, GO-Fe3O4 had no significant toxic effects on grapevine plants even at the concentration twice that of the highest dosage （1000 μg mL^-1） used in this study. Our work suggested that GO-Fe3O4 would offer an important opportunity to develop new approach for controlling plant diseases.

Structure-Activity Relationship, Cytotoxicity and Mode of Action of 2-Ester-substituted 1,5-Benzothiazepines as Potent Antifungal Agents

Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5- benzothiazepine （7a）. Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues （7a, 7b） were further studied by evaluating their cytotoxicity and mode of action （for 7a）. The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells.

Design,synthesis and biological evaluation of novel non-azole derivatives as potential antifungal agents

A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro antifungal activity with broad spectrum.The structure-activity relationships（SARs） of the derivatives were analyzed.Compound 9A2 exhibits better antifungal activity against 5 tested fungi in vitro than fluconazole,especially against Trichophyton rubrum and Microsporum gypseum.This study provides a series of novel lead compounds for the development of non-azole antifungal agents.

Controlling antifungal activity with light:Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin

Background During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents （voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin） against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. Methods The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. （5 species） were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35℃. MIC50, MIC90 and MIC range were acquired by Whonet 5.4 software. Results The MIC90 of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 μg/ml whereas the MIC90 against A. niger was 0.19μg/ml. For these four species, the MIC90 of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC90 of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC90 in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 μg/ml in all 7 strains tested. Conclusions The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

Effects of Two Curcuminoids on Candida albicans

Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth. Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C. albicans growth were first investigated and compared by microcalorimetry coupled with multiple analytical methods. The quantitative thermo-kinetic parameters obtained from these curves were analyzed to show difference of the actions. Results By analyzing the main parameters screened from principal component analysis together with 50% inhibiting concentration values, it was demonstrated that both CUR and DMC showed good antifungal activities and CUR was stronger. It was further concluded from structure-activity relationship that the existence of methoxy group might enhance lipophilicity of the mother nucleus, which made it easier for the molecular to enter into the cell membrane of fungi to inhibit its growth. Conclusion This study provides a new method for screening new antifungal agents with high efficacy and low toxicity. Meanwhile, it contributes to the application of curcuminoids as food additive, colorant, and drug. Microcalorimetry is real-time, online, and dynamic, and it could be used to characterize the subtle difference among the effects of synthetic and natural products on the vital process of fungi.

Efficacy and safety of micafungin for invasive candida infections：a meta-analysis of randomized controlled trials

Background Invasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients.Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus.We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.Methods We did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection.Seven trials involving 2913 patients were included in this analysis.Odds ratios （OR） and 95% confidence intervals （CI） were calculated.Results Micafungin was associated with significantly better treatment success compared with the comparator antifungal agents （modified intention to treat,2851 patients; random-effects model,OR 1.20,95% CI 1.00-1.45,P=0.0487）.In addition,micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation （OR 1.47,95% CI 1.08-2.00,P=0.01）.Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects （OR 0.94,95% CI 0.77-1.11）,fewer patients treated with micafungin withdrew from the studies because of adverse events （OR 0.64,95% CI 0.44-0.94）.Conclusions Micafungin has a good safety and tolerability profile,with an efficacy at least comparable to the other antifungal agents.Micafungin offers advantages over other agents for antifungal prophylaxis.Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

Small molecules for combating multidrug-resistant superbug Candida auris infections

Candida auris is emerging as a major global threat to human health. C. auris infections are associated with high mortality due to intrinsic multi-drug resistance. Currently, therapeutic options for the treatment of C. auris infections are rather limited. We aim to provide a comprehensive review of current strategies, drug candidates, and lead compounds in the discovery and development of novel therapeutic agents against C. auris. The drug resistance profiles and mechanisms are briefly summarized. The structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds will be illustrated in detail, and perspectives for guiding future research will be provided. We hope that this review will be helpful to prompting the drug development process to combat this fungal pathogen.

Screening of solanum surrattense for antibacterial,antifungal,phytotoxic and haemagglutination

OBJECTIVE： Plants produce a variety of useful bio- active materials that have been used to cure differ- ent ailments of human beings. With the same idea in mind, the crude methanolic extract and various fractions of Solanum surrattense were screened for antibacterial, antifungal, phytotoxic and heamag- glutination activities. METHODS： Standardized assays were followed for the determination of antibacterial, antifungal phy- totoxic and heamagglutination activity. RESULTS： The results of the antibacterial showed that crude methanolic extract was significantly ac- tive against Staphylococcus aureus （86%） The n- hexane fraction showed good activity against Pseu- domonas aerogenosa （66.6%） and Bacillus subtilus （66.6%）. The crude methanolic extract and various fractions were inactive against all test fungi. The crude methanolic extract, n-hexane, CHCI3 and aqueous fractions showed moderate phytotoxic ac- tivities of 46.67%, 40.00%, 33.34% and 33.34% re- spectively at 1000 pg/mL. The crude methanolic ex- tract and various fractions S. surrattense were un- able to aqqlutinate RBCs of the human blood indi-cating that this species lack phytolectins. CONCLUSION： The test sample showed significant antibacterial activity, no antifungal and heamagglu- tination activity while moderate phytotoxic was ob- served against Lemna minor L.

Synthesis and Bioactivity Evaluation of Novel N-Pyridylpyrazolemethanamine Derivatives

To further explore the structure-activity relationship（SAR） of amide bridge moeity of anthranilic diamides derivatives, a series of N-pyridylpyrazole derivatives was designed, synthesized and their biological activities were evaluated. The chemical structures of novel target compounds were confirmed by 1H nuclear magnetic resonance （N-MR）, 13C NMR and elemental analyses（EA）. Bioassay results of insecticidal activity demonstrated that the target compound 6h displayed 70% lethality rate against oriental armyworms at 200 mg/L. Moreover, most compounds displayed moderate to excellent antifungicidal activities against Fusarium oxysporumf sp. cucumerinum, Cercospora arachidicola Hori, Botryosphaeria dothidea, Alternaria solani, Gibberella zeae and Phytophthora capsici at 50 mg/L In particular, compound 6e showed 61.5% and 92.3% inhibition rate against Cercospora arachidicola Hori and Botryosphaeria dothidea, which was superior to the commercial positive control Chlorothalonil. These results will provide a potential clue for exploring novel high-effective agrochemicals.

Phytochemical investigation of medicinally important plants of the Pothohar region of Pakistan

OBJECTIVE:To report the phytochemical composition(flavonoids,phenolics,saponins,tannins,and terpenoids)and biological activities(antioxidant,phytotoxic,cytotoxic,antifungal activities)of medicinally important plants of Pothohar region.METHODS:In the current study various qualitative and quantitative phytochemical tests were conducted to investigate the phytochemical composition of plant extracts prepared in benzene,chloroform and methanol.The same extracts were further utilized in different biological activities i.e.,antioxidant[total antioxidant capacity,total reducing power,and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay],phytotoxicity(Radish seed bioassay),brine shrimp cytotoxicity and antifungal activities(against four pathogenic fungal strains).RESULTS:Phytochemical analysis indicate flavonoids,phenolics,saponins,tannins and terpenoids were present in almost all plants however,maximum amount of total phenolic and flavonoid contents was reported in of Malva parviflora and Lepidium pinnatifidum.Extracts of Malva parviflora and Lepidium pinnatifidum also depicted the superlative antioxidant activity(total antioxidant capacity,total reducing power,and DPPH scavenging activity).Maximum fungal growth inhibition was demonstrated by extracts of Centaurea calcitropa,Vicia sativa and Malva parviflora.The maximum cytotoxicity was shown by the extracts of Centaurea calcitropa.Moreover,for phytotoxicity assay the highest allelopathic potential was exhibited by extracts of Lepidium pinnatifidum.Solvents prejudiced results;the best results were obtained by Methanol followed by Chloroform and Benzene.CONCLUSION:Centaurea calcitropa,Vicia sativa,Malva parviflora and Lepidium pinnatifidum are most promising medicinal plants of Pothohar region for future studies.