Antioxidant and antifungal activities of marrubiin, extracts and essential oil from Marrubium vulgare L. against pathogenic dermatophyte strains.

OBJECTIVE: Medicinal plants extracts and plant-derived compounds are one of the natural sources for discovering new antifungal agents, the objectives of this work were to investigate for the first time the antidermatophytic, antipathogenic activities of methanol, acetone extracts, and essential oil of Marrubium vulgare L. grown in Tunisia and its active compound marrubiin on pathogenic for animals and humans, such as some dermatophytes and pathogenic for plants, and to evaluate antioxidant activities of different extracts with consideration to their chemical compositions. MATERIAL AND METHODS: Acetone and methanol extracts were evaluated by HPLC, the essential oil was also analyzed by GC/MS. PCL assay was used to determine the antioxidant activity. RESULTS: Results showed that methanol and acetone extracts exhibited a significant antioxidant activity (261.41 and 272.90µmol TE/g respectively), while the lowest one was observed in the case of marrubiin and essential oil. The antifungal activity of different extracts, marrubiin and essential oil at two concentrations (20 and 100µg/mL) were screened against the dermatophytes fungi Microsporum gypseum, Microsporum canis, Arthroderma cajetani, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum and against two fungi strains (Botrytis cinerea, Pythium ultimum). Among tested extracts, marrubiin at 100µg/mL showed about 50% inhibition for T. mentagrophytes and E. floccosum. The anti-phytopathogenic activity was also carried out, only marrubiin had in activity against B. cinerea at the highest dose (32.40%), while methanol extract of M.vulgare and marrubiin are able to increase the mycelial growth of P. ultimum at the highest concentration (45.15 and 40.30% respectively). CONCLUSION: In our study, we conclude that M.vulgare and marrubiin can be used as natural antioxidants and antifungal agent for treatment of skin dermatophyte infections.

Phloridzin derivatives inhibiting pro-inflammatory cytokine expression in human cystic fibrosis IB3-1 cells.

Cystic Fibrosis (CF) is the most diffuse autosomal recessive genetic disease affecting Caucasians. A persistent recruitment of neutrophils in the bronchi of CF patients contributes to exacerbate the airway tissue damage, suggesting that modulation of chemokine expression may be an important target for the patient's well being thus the identification of innovative anti-inflammatory drugs is considered a longterm goal to prevent progressive tissue deterioration. Phloridzin, isolated from Malus domestica by a selective molecular imprinting extraction, and its structural analogues, Phloridzin heptapropionate (F1) and Phloridzin tetrapropionate (F2), were initially investigated because of their ability to reduce IL-6 and IL-8 expression in human CF bronchial epithelial cells (IB3-1) stimulated with TNF-α. Release of these cytokines by CF cells was shown to be controlled by the Transcription Factor (TF) NF-kB. The results of the present investigation show that of all the derivatives tested, Phloridzin tetrapropionate (F2) is the most interesting and has greatest potential as it demonstrates inhibitory effects on the expression and production of different cytokines involved in CF inflammation processes, including RANTES, VEGF, GM-CSF, IL-12, G-CSF, MIP-1b, IL-17, IL-10 and IP-10, without any correlated anti-proliferative and pro-apoptotic effects.

Synthesis and biological evaluation of new vinyl ester pseudotripeptide proteasome inhibitors.

Here we report the synthesis and biological activities of new tripeptidic-based vinyl ester derivative proteasome inhibitors. Starting from Hmb-Val-Ser-Leu-VE prototype, we investigated P2 position and N-terminal substitution. The more effective inhibitors of the series showed remarkable inhibition and selectivity for the trypsin-like (beta2) subunit and were revealed to be specific for the proteasome. In vitro metabolic stability studies of the new vinyl ester analogues are also reported here.

HIV protease inhibitors: synthesis and activity of N-aryl-N'-hydroxyalkyl hydrazide pseudopeptides.

We describe the synthesis and activities of a series of pseudopeptides containing an N-aryl-N'-hydroxyalkyl hydrazide core structure to inhibit human immunodeficiency virus protease and viral replication. Of the series, compound Hmb-Leu-N(Bzl)-N(CH2-CH-OH)-rPro-Boc (24) displayed the greatest inhibitory potency (IC50 < 1 microM) and exhibited enzymatic resistance and stability in vitro.