An in vitro and in silico study of anti-dermatophytic activity of gossypol from fruits of Thespesia populnea (L.) Sol. ex Correa

Objective: To isolate, purify, and characterize gossypol from the fruits of Thespesia populnea (L) Sol. ex Correa, test its anti- dermatophytic activity, identify its targets on the dermatophyte, and confirm the binding of gossypol with the fungal target by molecular docking study. Methods: Gossypol from Thespesia populnea was characterized by high performance liquid chromatography, liquid chromatograph- mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance. The anti-dermatophytic activity of gossypol was tested against four different dermatophytes, viz. Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, and Microsporum gypseum. Trichophyton mentagrophytes was selected for further studies. The inhibitory mode of action of gossypol on Trichophyton mentagrophytes was determined by analyzing the modulation of gene expression in various pathways of the dermatophyte. Results: Gossypol inhibited all the dermatophytes. The minimum inhibitory concentrations were 12.5 μg/mL for Trichophyton mentagrophytes and Microsporum canis and 25 μg/mL for Trichophyton rubrum and Microsporum gypseum. The minimum fungicidal concentrations were 50 μg/mL for Trichophyton mentagrophytes, 100 μg/mL for Microsporum canis and Trichophyton rubrum, and 200 μg/mL for Microsporum gypseum. Gossypol inhibited the mRNA expression of metalloprotease (MEP4) and isocitrate lyase (ICL). The binding of gossypol with the enzymes was confirmed by molecular docking studies. The best docking poses were found and the low binding energies were recorded with the two target enzymes. Conclusions: Gossypol is a potential antifungal agent and can be further explored as an anti-dermatophytic drug.

Antifungal activity of chitooligosaccharides against the dermatophyte Trichophyton rubrum.

Antifungal activity against the dermatophytic fungus Trichophyton rubrum by a well-characterized chitooligosaccharides (COS) sample, hydrolyzed using a recombinant chitosanase, was investigated in vitro and in vivo. The minimum inhibitory concentration (MIC) of COS ranged between 0.25 and 0.50%, which was measured using a microdilution method. Analysis of inhibition rates using an agar diffusion method showed that treatment with 0.5% and 1% COS significantly suppressed T. rubrum cell growth (p<0.05 and p<0.01, respectively, in comparison with untreated control). Morphological changes and structural alterations of cells were observed by TEM. In vivo efficacy of COS in treatment of T. rubrum dermatophytosis was evaluated using a guinea pig model. Skin lesion scores revealed a strong, dose-dependent therapeutic effect of COS. The 5% COS group showed a reduction of skin lesions even greater than that of the positive control group treated with 1% fluconazole (FCZ). Histological analysis revealed no inflammation or tissue destruction in the groups treated with 5% COS or 1% FCZ. Hyperkeratosis was also observed, perhaps resulting from a defensive response of the tissue cells to COS. The findings indicate that COS has excellent potential for development of novel antifungal drugs for clinical treatment/remission of dermatophytoses.

A study on anti dermatophytic potential of selected ethno medicinalplants against Trichophyton rubrum, a common etiologic agent in and around Visakhapatnam region (India)

Objective: The purpose of this study was to evaluate the clinical patterns and etiology of dermatophytosis and the anti dermatophytic potentiality of some selected medicinal plants used by tribal people in and around Visakhapatnam region, India. Methods: 62 patients with dermatophytosis who attended the dermatology clinic of King George hospital, Visakhapatnam were studied. Isolation and identification was done by direct microscopic observation, cultural characteristics and by using biochemical tests in the microbiology laboratory. Some ethno medicinal plant parts like Albizia lebbeck bark, Annona reticulata leaf and bark, Cassia fistula leaf, Wrightia tinktoria bark and Couroupita guianensis leaf were tested for anti dermatophytic activity by agar well diffusion method and minimum inhibitory concentration (MIC) studies were carried out by broth dilution assay. Results: 51 patients out of 62 were positive (82.2%) by direct smear and culture. Tinea corporis was the most common dermatophytosis which was predominantly caused by Trichophyton rubrum in and around Visakhapatnam. Two dermatophyte species were isolated and identified. Trichophyton rubrum was the most frequent isolate (58.8%) followed by Trichophyton mentagrophytes (19.6%). Albizia lebbek bark, Annona reticulata bark and leaf extracts showed inhibitory against T. rubrum while Cassia fistula leaf extract did not show significant inhibitory activity. Wrightia tinktoria bark and Couroupita guianensis leaf extracts did not show inhibitory activity. Conclusions: The results showed that tinea corporis was the most common dermatophytosis in and around Visakhapatnam region. Trichophyton rubrum was the most common etiologic agent. Albizia lebbek bark, Annona reticulata leaf and bark extracts showed potential inhibitory activity against Trichophyton rubrum than other tested ethno medicinal plants.