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A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-a]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated in vitro for their inhibition properties against a representative panel of hCA isoforms (hCA I, II, IV, IX, and XII). The target tumour-associated isoforms hCA IX and XII were potently inhibited with KIs in the low nanomolar range of 5–96 nM and 4–72 nM, respectively. Compounds 1d, 1j, 1v, and 1x were the most potent hCA IX inhibitors with KIs of 5.1, 8.6, 4.7, and 5.1 nM, respectively. Along with derivatives 1d and 1j, compounds 1r and 1ab potently inhibited hCA XII isoform with KIs in a single-digit nanomolar range of 8.8, 5.4, 4.3, and 9.0 nM, respectively. Compounds 1e, 1m, and 1p exhibited the best selectivity against hCA IX and hCA XII isoforms over off-target hCA II, with selectivity indexes ranging from 5 to 14. [ABSTRACT FROM AUTHOR]

There is extensive ethnobotanical information on Ocimum campechianum as it is widely used by the natives of Central and South America and the Amazon. Although many of its traditional uses have been confirmed, studies are still scarce and scattered. Therefore, the main focus of this review is to provide a comprehensive and critical analysis of the state of the art about ethnobotanical, phytochemical, pharmacological, and toxicological knowledge of O. campechianum. This overview offers a starting point for further studies of possible health applications that meet modern needs for human well-being. Future challenges should be focused on research based on new approaches for the understanding of its global benefits. It is suggested to promote studies on multiple herbal remedies, and the antiproliferative and cytotoxic activities of the compounds, as well as new strategies that relate phytochemistry with bioactivity, toxicological evaluations on acute and long-term toxicity, mechanisms of action, pharmacodynamic, and pharmacokinetic studies. Finally, a focus on the possible application of O. campechianum as a biopesticide for the sustainable protection crop of crops and suggests the need to explore new uses of its essential oil for the treatment of foodborne pathogens. [ABSTRACT FROM AUTHOR]

To assess the ocular surface status after treatment with urea/crosslinked hyaluronate (U-HACL) tear substitute in dry eye (DE) patients. Seventeen DE patients were included in the study. They instilled U-HACL drops three times/day for 2 months. Symptoms (by OSDI and VAS), osmolarity, tear film (through Schirmer and tear film breakup time), corneal and conjunctival damage (with NEI and van Bijsterveld scores), impression cytology (number of PAS positive cells and MUC-4 immunostaining), and tear sampling were analyzed pre- and post-treatment. After the treatment, there was a significant improvement of VAS (7.16 ± 2.59 vs. 3.94 ± 2.23), OSDI (56.96 ± 25.97 vs. 29.94 ± 20.15), Schirmer (8.22 ± 6.86 vs. 10.66 ± 6.92), TFBUT (3.16 ± 2.28 vs. 5.55 ± 2.47), NEI (7.16 ± 2.50 vs. 2.88 ± 2.80), and van Bijsterveld (10.27 ± 4.25 vs. 6.5 ± 3.79) score, p < 0.01. There was a significant increase of PAS positive cells and MUC-4 (respectively, 44.21 ± 14.8 vs. 67.0 ± 10.1 and 49.79 ± 20.0 vs. 75.9 ± 20.7), p < 0.01. The rise of MUC-4 expression probably contributed to the increase in ocular wettability and amelioration of clinical parameters following the administration of U-HACL eye drops. [ABSTRACT FROM AUTHOR]

Amaranthus spp. (Amaranthaceae family), known as amaranth, are plants native of Central America, today produced in many parts of the world. due to their popularity popular as a health food. Because of its composition, amaranth can be considered to be attractive not only as a food but also for pharmaceutical and cosmetics uses. To date, antifungal activity of amaranth extracts has not been totally investigated, therefore the scope of this study was to evaluate the antifungal effect of the apolar fraction from Amaranthus cruentus L. seeds extract, alone and in association with antifungal drugs terbinafine, a common antifungal agent, which itself has only fungistatic effect on Candida albicans strains without exerting fungicidal activity. Our results demonstrate that this amaranth oil in combination with terbinafine has synergic fungistatic and fungicidal activity, with FICI of 0.466 and 0.496, respectively. No fungistatic and fungicidal activity of terbinafine alone at concentrations up to 64 μg/mL and amaranth oil alone at concentrations up to 2000 μg/mL, against all tested C. albicans strains, were observed. does not show activity towards Candida albicans strains but it can effectively potentiate the antifungal activity of terbinafine, a common antifungal agent which itself This result suggests the possible application of amaranth oil in the preparation of formulations with terbinafine for topical use. [ABSTRACT FROM AUTHOR]

A comprehensive study on essential oil samples extracted from Ridolfia segetum Moris (Apiaceae) collected in Tarquinia (Italy) is reported. In this study, a 30-hour, fractionated, steam distillation procedure for essential oil preparation was applied. The gas chromatographic-mass spectrometry analysis showed monoterpene o-cymene and phenylpropanoid dill-apiol as the major essential oil's constituents revealing a new chemotype dependent on extraction duration. Great impact of the duration of the distillation process on chemical profile of essential oil was observed; prolonged distillation gives chemically more diverse essential oil samples. Preliminary microbiological evaluations of the essential oils samples revealed some activity, although not high, against Candida albicans. [ABSTRACT FROM AUTHOR]

A comprehensive study on essential oil samples of Foeniculum vulgare Miller from Tarquinia (Italy) is reported. A 24-h systematic steam distillation was performed on different harvested samples applying different extraction times. The GC-MS analysis of the residue outcome showed o-cymene, α-phellandrene, α-pinene and estragole as the major constituents. The predominance and continued presence of o-cymene makes this fennel oil a rather unique chemotype. An evident correlation between the antifungal activity and phenological stage is demonstrated. The most active fractions were particularly rich in estragole, as well as a significant amount of fenchone that possibly exerts some additive effect in the expression of overall antifungal potency. Pre-fruiting material produced oil particularly rich in o-cymene. With reference to the duration of the extraction, the maximum amount of oil was released within the first 3 h, whereas the reproductive phase material needed at least 6 h for the extraction. [ABSTRACT FROM AUTHOR]

A study on essential oil fractions of the Western Balkan endemic Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood collected in Montenegro is reported. The 24-h systematic steam distillation extraction procedure was performed. The gas chromatographic/mass spectrometric (GC/MS) analysis of the fractions showed γ-elemene and spathulenol as two main constituents, revealing a new chemotype of this plant species. Although varying in the content of these two main compounds, which makes the fractions quite different between each other, evaluation of the anti-Candida activity showed the lack of any significant efficacy. [ABSTRACT FROM AUTHOR]

An ever-increasing incidence of skin neoplastic diseases is registered. Therefore, it is important to protect the skin from the UV radiation that reaches the epidermis and dermis but also to block ROS generated by them. Our attention was attracted in developing new compounds provided with both UV filtering and antioxidant capacities. To this end, 2-phenyl-1H-benzimidazole-5-sulfonic acid (PBSA), a known UV filter, was selected as lead compound for its lack of antioxidant activity, high water solubility and good safety profile. PBSA was sequentially modified introducing hydroxyls on the phenyl ring and also substituting the functional group in position 5 of the benzimidazole ring. At the end of the synthetic study, a new, very potent class of antioxidants has been obtained. Surprisingly some of the developed molecules, while devoid of significant UV-filtering activity was endowed with potent UV-filtering booster capability if associated with known commercial UVB and UVA filters. [ABSTRACT FROM AUTHOR]

High-performance thin-layer chromatography (HPTLC) is an innovative, green, reliable, and rapid method for the characterization of complex sugar mixtures. For research into sustainable nontimber forest products,Adansonia digitatadry fruit pulp in this proof-of-concept study was used to demonstrate this method due to its reported high nutritional value and prebiotic activity. Chromatographic separations were performed on (20 × 10 cm2) HPTLC glass plates with diol stationary phase, using a 15-step gradient by mixing solutions acetone/acetonitrile 1:1, and ultrapure water for enzymatic degradation products. Instead, monosaccharide moieties were separated on HPTLC silica gel 60 F254over isocratic mode with 80 mm of eluent front composed of acetonitrile/acetic acid/water 63/33/5 v/v/v. Identification and quantification were performed by densitometry acquisitions at 400 nm after opportune derivatization. Our research highlighted that this technique can be used as a standard method to gain new insights into inulin determinations, with several advantages over existing conventional liquid chromatography. The development of innovative methods for the characterization of biopolymers is crucial, for food and nutraceutical industry and for quality control of phytochemicals. Characterization of such materials, up until now, has been done by mass difference and so accurate analytical methods were lacking. [ABSTRACT FROM AUTHOR]

[image omitted] A rapid and efficient synthesis of 1-benzyl-2-difluoromethyl-piperazine is herein described. The new pathway has the advantage of avoiding orthogonal protection at the two piperazine nitrogen atoms; therefore it is suitable for access to several 1-benzyl 2-substituted piperazines starting from the simple commercially available N,N'-dibenzylethylendiamine. [ABSTRACT FROM AUTHOR]

The antifungal activity of eight pyrazolo[3,4- c]isothiazole derivatives was evaluated on five dermatophytes: three were of an anthropophilic species (i.e., Epidermophyton floccosum, Trichophyton rubrum, and Trichophyton tonsurans) and two were of a geophilic species (i.e., Microsporum gypseum and Nannizzia cajetani). The new compounds proved to be unlikely effective in inhibiting the growth of the different strains. In general, the fungi parasitic on man were more sensitive than the geophilic species. This fact can be positive for a possible practical-therapeutic utilization of this class of compounds. To verify their possible use against fungi of medical interest, the most interesting substance at low doses, 6-(4-chlorophenyl)-4-methyl-6 H-pyrazolo[3,4- c]isothiazol-3-amine, was chosen to perform in vitro genotoxicity tests using the following: Salmonella/microsome test (SAL), sister chromatid excange test (SCE), cytokinesis-blocked micronucleus test (CBMN), and its improvement (Ara-C/CBMN). The compound showed no mutagenic activity at low doses, whereas at the highest dose (100 µµg/mL), it caused a generalized cytotoxic effect. The high growth inhibition exerted on fungi at the lowest dose and the concomitant lack of genotoxicity, at least until the dose of 50 µµg/mL, might suggest the compound as a safe candidate as an antidermatophytic substance. [ABSTRACT FROM AUTHOR]

Context: The diseases of plants and humans due to pathogenic fungi are increasing. Among the substances used to combat fungi, the azoles are of primary interest, both in agricultural field both in health. To avoid fungal resistance phenomena, the synthesis and tests of new derivatives are necessary. Objective: This article discusses the synthesis and the antifungal activity of pyrazolo[3,4- c]isothiazole and isothiazolo[4,3- d]isoxazole derivatives against three fungi that are pathogenic only for plants and two fungi that are opportunistic in humans and plants. Materials and Methods: The compounds were prepared starting from 2-cyano-3-ethoxy-2-butenethioamide. The antifungal activity of the compounds was determined by measuring the inhibition of growth of the fungi tested at 20, 50, and 100 µµg/mL in comparison with the controls. Results: Results demonstrated that several compounds were able to control the mycelial growth of the tested fungi, even if they showed different sensitivity to the different azole-derivatives. In general Magnaporthe grisea (T.T. Hebert) Yaegashi & Udagawa was the most sensitive fungus, being blocked almost entirely by 4-chloro derivative even at 20 µµg/mL, a concentration at which the reference commercial compound tricyclazole was nearly ineffective. Discussion and conclusion: These findings demonstrate that the pyrazolo[3,4- c]isothiazole derivatives have a wide spectrum of activity on phytopathogenic and opportunistic fungi. In particular the 4-chloro derivative seems to have a great potential as new product to combat M. grisea in the agricultural field. [ABSTRACT FROM AUTHOR]

The synthesis of model 7 deazapurine derivatives related to tubercidin and toyocamycin has been performed. Tubercidin derivatives were obtained by simple conversion of the amino group of the heterocyclic moiety of the starting 7-deazadenosine compounds, into a hydroxyl group. Preparation of toyocamycin derivatives was accomplished by treatment of the silylated 6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-4-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose. The glycosylation reaction afforded a mixture of 8-bromo 7-cyano 2',3',5' tri-O-benzoyl 7-deazainosine and 6-bromo-5-cyano-3-(2',3',5'-tri-O-benzoyl-β-d-ribofuranosyl)pyrrolo[2,3-d]-pyrimidin-4-one isomers: The structures were assigned on the basis of NMR spectroscopy studies. Next deprotection treatment gave the novel 7-deazainosine ribonucleosides. [ABSTRACT FROM AUTHOR]

There is a body of evidences demonstrating, in biological systems, a cooperative interaction between tocopherols and carotenoids. FeAOX-6 is a novel antioxidant that combines the chroman head of α-tocopherol and a fragment of the isoprenyl chain of lycopene. We have tested its antioxidant effect on different radical species generated in a chemical system, where peroxyl, alkoxyl and methyl radicals are generated by the ferrous ion-mediated decomposition of tert -butyl hydroperoxide. We found that FeAOX-6 has the same effectiveness of α-tocopherol in quenching peroxyl radical with no contribution by lycopene. The antioxidant activity of FeAOX-6 on alkoxyl and methyl radicals is comparable to that of the equimolar mixture of the parent compounds. Lycopene is able to quench alkoxyl radical, while it has no effect on peroxyl radical, showing a different antioxidant activity compared to other carotenoids, such as β-carotene and lutein. [ABSTRACT FROM AUTHOR]