Oxidized mC modulates synthetic lethality to PARP inhibitors for the treatment of leukemia.

TET2 haploinsufficiency is a driving event in myeloid cancers and is associated with a worse prognosis in patients with acute myeloid leukemia (AML). Enhancing residual TET2 activity using vitamin C increases oxidized 5-methylcytosine (mC) formation and promotes active DNA demethylation via base excision repair (BER), which slows leukemia progression. We utilize genetic and compound library screening approaches to identify rational combination treatment strategies to improve use of vitamin C as an adjuvant therapy for AML.

B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease.

Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases.

Antifungal activity of Lavandula angustifolia essential oil against Candida albicans yeast and mycelial form.

The antifungal activity of the essential oil of Lavandula angustifolia Mill. (lavender oil) and its main components, linalool and linalyl acetate, was investigated against 50 clinical isolates of Candida albicans (28 oropharyngeal strains, 22 vaginal strains) and C. albicans ATCC 3153.

Effect of propolis on virulence factors of Candida albicans.

Propolis is a resinous substance collected by honeybees from plant sources. Its antimicrobial activity has been well documented but little is specifically known about its activity on virulence factors of Candida albicans. The aim of this work was therefore to evaluate in vitro the propolis effect on yeast-mycelial conversion (Y-M), extracellular phospholipase activity and fungal adhesion to epithelial cells.

In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi.

The antifungal activity of Melaleuca alternifolia Maiden (Myrtaceae) essential oil against yeasts (Candida spp., Schizosaccharomyces pombe, Debaryomyces hansenii) and dermatophytes (Microsporum spp. and Tricophyton spp.

Propyl gallate increases in vitro antifungal imidazole activity against Candida albicans.

We looked at the in vitro effect of an antioxidant, propyl gallate (PG), on the antifungal activity of miconazole sulphosalicylate, econazole sulphosalicylate and ketoconazole against 40 clinical isolates of Candida albicans. The combination of imidazole and PG gave MIC values 10-150 times lower than those of imidazole alone. The optimal conditions for this enhanced activity were pH 6.

Anticandidal activity of SPA-S-843, a new polyenic drug.

The activity of a new, soluble and stable polyene (SPA-S-843) against Candida albicans was assessed by contact and culture tests and by inhibition of germ-tube formation. The drug demonstrated a higher contact activity and lower MICs than amphotericin B. This antimicrobial activity was more evident under acid pH and low ionic strength.

Antifungal activity of ketoconazole and other azoles against Malassezia furfur in vitro and in vivo.

The in vitro activity of several antifungal agents (ketoconazole, miconazole, econazole, fenticonazole, itraconazole, fluconazole) in routine clinical use against Malassezia furfur infections has been studied with freshly isolated strains of M. furfur from pityriasis versicolor lesions. The results indicate that the drugs tested exert a good activity, and both ketoconazole and itraconazole appear very active (0.

In vivo and in vitro antifungal activity of the polyene derivative SPA-S-753 against encapsulated form of Cryptococcus neoformans.

The in vitro and in vivo activity of SPA-S-753 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate), a new water soluble polyene, was compared with amphotericin B against Cryptococcus neoformans in encapsulated (K) and nonencapsulated (N) morphological forms. In vitro tests against 17 isolates of C. neoformans (in K or N form) showed that SPA-S-753 activity is about ten times higher than that of amphotericin B.

Antifungal agents. 9. 3-Aryl-4-[alpha-(1H-imidazol-1-yl)arylmethyl]pyrroles: a new class of potent anti-Candida agents.

A new class of potent antifungal agents, namely, 3-aryl-4-[alpha-(1H-imidazol-1-yl)arylmethyl]-pyrroles, is described. These compounds are related to bifonazole and pyrrolnitrin, two compounds belonging to the class of antimycotic drugs. The synthesis of the title pyrroles has been performed starting from 1,3-diaryl-2-propen-1-ones, which were reacted with tosylmethyl isocyanide to give 3-aroyl-4-arylpyrroles.

Antimicrobial contact activity of econazole sulfosalicylate.

The aim of this investigation was to compare the contact action of econazole sulfosalicylate (E-SSA) on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, T. cutaneum, Pityrosporum sp.), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Citrobacter freundii) with that exerted by econazole nitrate (E-NIT).

Increased in vitro sensitivity of Candida albicans to fluconazole.

Sodium dioctyl sulfosuccinate (SDSS), an anionic surfactant used at a non-antimicrobial concentration, increased the sensitivity of Candida albicans to fluconazole in complex media (such as Sabouraud). The conditions were assessed to determine the in vitro sensitivity to fluconazole. In this connection, the use of a liquid medium at a non-alkaline pH is important.

Investigations of the activity by contact of miconazole sulfosalicylate.

The in-vitro antimicrobial activity of miconazole sulfosalicylate (M.SSA) has been investigated on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus niger, Trichophyton mentagrophytes), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Proteus vulgaris) in comparison with miconazole nitrate (M.NIT).

[Antimicrobial activity exerted by sodium dichloroisocyanurate].

Sodium dichloroisocyanurate is a chlorinated cleaner. It was used for swimming pool sanitation and for the sterilisation of linen. Not recently ago sodium dichloroisocyanurate has substituted hypochlorite for the sterilisation of infant feeding bottles and teats.

[Antimicrobial characteristics of a tincture of dequalinium chloride].

Dequalinium is a quaternary ammonium salt. From about 30 years Dequalinium (D.C.

The antibacterial activity of a new 3-azinomethyl-rifamycin.

The new 3-azinomethyl-rifamycin, SPA-S-565, was shown to exert an effective antibacterial activity in vitro comparable to that of rifampicin. In fact, the antibacterial activity of SPA-S-565 against numerous Gram-positive cocci belonging to Staphylococcus and Streptococcus species as well as against 20 strains of Mycobacterium tuberculosis, was similar to that of rifampicin. In Swiss albino mice intraperitoneally infected with Staphylococcus aureus Oxford strain or Streptococcus pyogenes, the protective activity of SPA-S-565 and rifampicin was quite remarkable, and no significant difference was noted between the two antibiotics.

A study of the antifungal activity of LY121019, a new echinocandin derivative.

LY121019 is a cyclic peptide antibiotic of the echinocandin group, which is characterized by strong anti-Candida activity (in particular against Candida albicans) as well as by low experimental toxicity. Its anti-Candida activity is thought to be due to an inhibition of the synthesis of beta-glucan, an essential cell wall polysaccharide. The different composition of culture media or the presence of animal serum did not show adverse effects on LY121019's anti-Candida activity and the addition of reducing compounds such as cysteine and hydroquinone did not manifest a negative influence.

Itraconazole activity against fungal germination.

Itraconazole was found to be superior to ketoconazole in its antifungal activity in vitro against Hyphomycetes and Candida. In particular, complete inhibition of germination of Candida albicans and Aspergillus spp. by a lower dose of itraconazole can explain the better activity in vivo of this drug.

Itraconazole: increased activity by chlorhexidine.

Chlorhexidine increases the activity of itraconazole against Candida isolates; itraconazole-chlorhexidine combinations show synergistic activity in culture media. The activity of itraconazole is discussed.

Microbiological perspective of ketoconazole.

The analysis of the results obtained in our trials, which took into account different experimental conditions, suggests that ketoconazole is a very effective anti-Candida drug. In particular, ketoconazole inhibits the development of the hyphal form of C. albicans which is highly invasive.

[Antibacterial and antifungal agents. IV. Synthesis and antifungal activity of econazole analogs with pyrrole structure].

The synthesis of analogues of antifungal econazole with a pyrrole moiety starting from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanone and from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanol is described. Results of antimicrobial screening of the new derivatives in comparison with econazole are also reported.

In vitro and in vivo antifungal activity of the combination methylpartricin-5-fluorocytosine.

In vitro studies on the antifungal activity exerted by the combinations SPA-S-222 (a hydrosoluble derivative of the polyene antibiotic methylpartricin) and 5-fluorocytosine evidence a favourable interaction against the formation of germ-tube in Candida albicans; against Cryptococcus neoformans and 5FC induced-resistant strains of Candida albicans. In the experimental infections with Candida albicans and Cryptococcus neoformans a significantly favourable interaction was exerted by polyene-5FC combinations.

[Effect of propyl gallate on the antibacterial activity of meclocycline sulfosalicylate].

Propyl gallate shows little antibacterial activity however it markedly potentiates the activity of meclocycline against Pseudomonas, Proteus, Serratia, Escherichia coli and Klebsiella strains. The potentiating effect of propyl gallate is seen especially with resistant strains whereas sensitive strains of Salmonella do not manifest a potentiating effect on meclocycline by propyl gallate. The mechanism of action of propyl gallate is discussed.