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Cryptococcosis is a potentially fatal fungal disease which has aggrandized with the emergence of AIDS and antifungal resistance. The currently used antifungals lack the broad-spectrum activity and result in several toxicities during long treatment regimens. Thus, the present study aims to evaluate the antifungal activity of cinnamaldehyde against Cryptococcus neoformans var. grubii, the etiological agent of the disease. Quantitative and qualitative in vitro fungal susceptibilities were carried out by minimum inhibitory concentration assay, flow cytometric analysis, and confocal microscopy. Micromorphological alterations were studied through scanning electron and light microscopies. "In vivo" antifungal efficacy of cinnamaldehyde was assessed. Cinnamaldehyde showed antifungal activity against C. neoformans in a dose-dependent manner. A concentration of 1.37 mg/mL of cinnamaldehyde was found to be inhibitory and fungicidal while the low concentration (0.68 mg/mL) was found to induce micromorphological changes and formation of giant/titan-like cells in this pathogen. The reparative activity of cinnamaldehyde and its ability to prolong the life even after the advent of cryptococcal meningitis in mice was also noticed. This study suggests potent anti-cryptococcal activity of cinnamaldehyde. Though, it has a couple of limitations like allergy and low bioavailability. However, these problems can be circumvented by developing suitable analogs of the compound. It, therefore, could be used as a therapeutic option against cryptococcosis and cryptococcal meningitis. Moreover, the evaluation of its pharmacokinetic and pharmacodynamic properties is desirable.

We describe Mus musculus castaneus as a new mammalian host for Cryptococcus neoformans var. grubii (VNI). Eighteen apparently healthy adults and pups of the rodent were collected from human dwellings in Varanasi, a city of India. Both clinical and behavioral examinations of the rodents did not reveal any sign of the disease. Among visceral organs, histological examination of only liver exhibited the presence of single celled, encapsulated, Southgate's mucicarmine positive fungal structures consistent with C. neoformans. Nevertheless, culture of tissue homogenates of brain, lungs, liver, and kidneys yielded white colonies on Sabouraud's dextrose agar and brown mucoid colonies of C. neoformans on Staib's and Tobacco agar media. The pathogen was isolated from habitat soil as well as fresh faeces of the animals. All isolates were urease positive, nitrate and canavanine-glycine bromothymol blue negative, exhibited phenoloxidase activity and grew at 37°C. The isolates were identified as C. neoformans var. grubii with ITS primers and unique marker (GACA)4. The pathogen when inoculated in immunosuppressed mice showed low pathogenicity. To our knowledge, we for the first time report case cluster of Mus musculus castaneus as new passenger host for C. neoformans var. grubii (VNI)., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A series of novel coumarin‐amino acid conjugates was synthesized and structural characterization was done by various spectroscopic methods. All the conjugates were screened for their antifungal activity against five fungal strains namely T. rubrum, A. niger, A. fumigatus, A. flavus and C. albicans by two‐fold serial microdilution method. Some of them showed significant activity with MIC values in the range of 6.25–25 μg/mL. Notably, compound 5 e showed potential antifungal effect against three tested strains with MIC's in the range of 6.25–12.5 μg/mL. The molecular docking studies showed that some conjugates possessed good binding affinity with the modelled receptor of integrin‐like protein of Cryptococcus neoformans var. grubii. Compounds 5 d and 5 e also exhibited good binding efficiency with the Candida spp. cell wall associated proteins in in vitro binding assay. Additionally, in silico physicochemical parameters such as lipophilicity and pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) of the synthesized compounds were also evaluated. [ABSTRACT FROM AUTHOR]

Cryptococcosis is amongst potentially deadly diseases whose impact has aggrandized with the advent of AIDS and antifungal resistance. Antifungals used presently are short of broad spectrum activity and furthermore are involved in several side effects. Henceforth, the present manuscript focuses on the evaluation of antifungal activity of bacitracin against Cryptococcus neoformans var. grubii, the causative agent of the disease. Minimum inhibitory concentration, flow cytometric analysis and confocal microscopy were used to determine the in-vitro fungal susceptibilities. Light microscopy was used to determine the changes in the micromorphology of the fungal organism. Swiss mice were used for testing the efficacy of bacitracin in-vivo. Bacitracin showed cidal activity against C. n. grubii at 5.5 mg/ml which is on the higher side but on testing under in-vivo conditions it was observed that doses as high as 15 mg/kg bw/day did not show any adverse effect in the body. Better survival rate of the bacitracin treated mice, lowering of the fungal load and changes showing improvement in the tissue morphology depicts the mild anticryptococcal activity of bacitracin. Although, bacitracin has proved to be a potent antifungal yet there are several limitations like low bioavailability and its peptide nature. However, these problems can be limited by developing suitable analogs of the compound. [ABSTRACT FROM AUTHOR]

Drug development is a dynamic field which undergoes changes continuously. The past decade or so has witnessed huge strides in the field of screening of the drugs as well as target and ligand identifications but unfortunately this has not led to useful drugs. Many diseases still remain untreatable because we do not have proper drugs against them. In case of fungi the situation is graver due to the limited drug targets peculiar to fungi. Thus, in order to combat the fungal diseases the need of the hour is to develop new antifungals that have fewer side effects and broad spectrum activity. The current work deals with closantel, a veterinary drug targeting chitinase, which is utilized as a therapeutic option against helminths. The fact that chitin is an important constituent of the cell wall of the fungi also and it undergoes regular degradation and remodelling through an enzyme called fungal chitinase motivated the authors to test the efficacy of closantel against fungal chitinase. In the present study Cryptococcus neoformans has been used as a model organism against which the antifungal activity of closantel has been tested. In-silico studies carried out using PatchDock and FireDock predicted the global energy (binding energy)involved in docking closantel on chitinase as -47.58 Kcal/mol. Further, the results obtained through the in-silico studies were validated by the minimum inhibitory concentration assay (MIC). It was observed that 736 (±7.024) μg/ml of closantel can inhibit the cryptococcal growth by 80% (MIC80). [ABSTRACT FROM AUTHOR]

Griseofulvin is a well known drug against dermatophytes. It is particularly prescribed for an infection called scrap ringworm or tinea capitis. In general, griseofulvin inhibits the tubulin protein that is responsible for the cell division. Not much is known about the effect of griseofulvin on Cryptococcus neoformans. Therefore, the authors made an effort to check the activity of griseofulvin against it. The webservers (T-Coffee, Bluues simulation and CASTp) and software (Autodock 4.0) have been used in order to determine the activity of griseofulvin against the beta subunit of tubulin protein of C. neoformans. The results obtained from the in silico studies show a high affinity of griseofulvin towards the beta chain of tubulin protein. The negative value of binding energy (-9.02 kcal/mol) also shows that the complex is thermodynamically favourable and stable. These in silico results were further validated by MIC assay showing 74.1% inhibition of C. neoformans (isolate no. 5) against griseofulvin. The present study reports that apart from dermatophytes, the drug has significant effect on C. neoformans and it may be used in the combinatorial therapy against the same. [ABSTRACT FROM AUTHOR]