A new nanoemulsion formulation improves antileishmanial activity and reduces toxicity of amphotericin B

This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL). When the NE was submitted to gradual increases in pressure, the PI values and droplet size decreased. The droplet size (～145?nm) was lower than that obtained in previous studies. The zeta potential was negative and the EE was almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB-loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at 2?mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same dose, did not result in any sign of acute toxicity, promoting a significant reduction in parasite burden as compared to the C-AmB. These findings suggest that this new AmB-loaded NE constitutes an attractive alternative for the treatment of VL due to improved efficacy and lower toxicity.     

Phenatic acids A and B, new potentiators of antifungal miconazole activity produced by Streptomyces sp. K03-0132

Two new phenols, designated phenatic acids A and B, were isolated along with known actiphenol, from the culture of Streptomyces sp. K03-0132 by solvent extraction, silica gel column chromatography and HPLC. Their structures were elucidated by spectroscopic analyses including mainly various NMR experiments. They have a common 1-hydroxy 2, 4-dimethyl benzene ring. These compounds potentiate miconazole activity against Candida albicans. Phenatic acid B also showed moderate antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Bacteroides fragilis and Acholeplasma laidlawii.     

Physico-chemical and microbiological comparison of nystatin, amphotericin A and amphotericin B, and structure of amphotericin A

Two polyene antibiotics, nystatin and amphotericin A, were compared by physico-chemical and microbiological methods. The two antibiotics were found to have the same molecular weight, 926, by plasma desorption and electron-impact MS. However, 13C NMR spectrometry and HPLC studies indicated that the two molecules are different. The 200 MHz NMR studies indicated a chemical environment of 24 carbons of amphotericin A identical with that of the carbons of amphotericin B and nystatin. The structure of amphotericin A is identical with that of amphotericin B, except that there is a single bond between carbons 28 and 29 instead of a double bond, as shown by two-dimensional NMR studies.     

Halophilols A and B, two new stilbenes from Iris halophila

A new monomeric stilbene, halophilol A (1), and a new tetrastilbene, halophilol B (2), along with three known oligostilbenes were isolated from the seeds of Iris halophila. Their structures were established on the basis of the spectral data. The oligostilbene skeleton is encountered for the first time in the Iridaceae family. Bioactivity tests showed that 1 had moderate cytotoxicity against KB and HMEC cell lines (IC50 = 17.28 microM, 22.47 microM respectively), while 2 was inactive.     

Miyoshianines A and B,two new lycopodium alkaloids from Huperzia miyoshiana

Two new Lycopodium alkaloids, miyoshianines A and B, together with five known alkaloids, lycopodine, lycodoline, 12-epilycodoline, clavolonine, and flabelliformine, were isolated from Huperzia miyoshiana (Makino) Ching (Huperziaceae). Their structures were determined by means of spectroscopic techniques.     

Terrestrinins A and B, two new steroid saponins from Tribulus terrestris

Two new steroid saponins, named terrestrinins A (1) and B (2), along with six known compounds were isolated from the Chinese medicine herb Tribulus terrestris, and their chemical structures were elucidated as 26-O-beta-D-glucopyranosyl-(25S)-furostan-4(5),20(22)-diene-3,12-dione (1) and 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-3beta,22alpha,26-triol-3-O-beta-D-xylopyranosyl(1 --> 3)-[(beta-D-xylopyranosyl(1 --> 2)]-beta-D-glucopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-galactopyranoside (2) on the basis of spectroscopic techniques.     

锈毛野桐中的两个新二萜anomalusin A和anomalusin B(英文)

从锈毛野桐中分离得到两个新的ent-rosane型二萜anomalusin A(1)和anomalusin B(2),以及10个已知化合物。化合物1和2的结构和相对构型通过波谱学方法确定,它们的绝对构型通过CD谱确定。     

Asparosides A and B,two new steroidal saponins from Asparagus meioclados

Asparosides A ( 1 ) and B ( 2 ), two new saponins, were isolated from the roots of Asparagus meioclados . On the basis of chemical and spectroscopic evidence, their structures were elucidated as 23- O - f -arabinopyranosyl-(5 g ,25s)-spirostan-3 g ,23 f -diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside and 26- O - g -glucopyranosyl-5 g -furost-20(22)-ene-3 g ,26-diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside, respectively.     

Asparosides A and B,two new steroidal saponins from Asparagus meioclados

Asparosides A (1) and B (2), two new saponins, were isolated from the roots of Asparagus meioclados. On the basis of chemical and spectroscopic evidence, their structures were elucidated as 23-O-alpha-arabinopyranosyl-(5beta,25s)-spirostan-3beta,23alpha-diol-3-O-[beta-D-xylopyranosyl(1-->4)]-beta-D-glucopyranoside and 26-O-beta-glucopyranosyl-5beta-furost-20(22)-ene-3beta,26-diol-3-O-[beta-D-xylopyranosyl(1-->4)]-beta-D-glucopyranoside, respectively.     

Tensidols, new potentiators of antifungal miconazole activity, produced by Aspergillus niger FKI-2342

Two new furopyrrols, designated tensidols A and B, were isolated from the culture broth of Aspergillus niger FKI-2342 by solvent extraction, silica gel column chromatography and HPLC. Their structures were elucidated and shown to have the common skeleton of 6-benzyl-6H-furo[2,3-b]pyrrole. Tensidols A and B potentiated miconazole activity against Candida albicans. Tensidols also showed moderate antimicrobial activity only against Pyricularia oryzae.     

Leucoxenols A and B,two new phenolics from Bornean medicinal plant Syzygium leucoxylon

The medicinal plant, Syzygium leucoxylon or commonly known as Obah found in North Borneo was considered as traditional medicine by local committee. Two new phenolics, leucoxenols A (1) and B (2) were isolated and identified as major secondary metabolites from the leaves of S. leucoxylon. Their chemical structures were elucidated based on spectroscopic data such as NMR and HRESIMS. Furthermore, these compounds were active against selected strains of fungi.     

Fusaristatins A and B, two new cyclic lipopeptides from an endophytic Fusarium sp

Two new cyclic lipopeptides, fusaristatins A (1) and B (2) were isolated from rice cultures of a Fusarium sp. YG-45 in the course of a screening of endophytic fungi. Their structures of 1 and 2 were determined by spectroscopic methods. 2 showed a moderate inhibitory effect on topoisomerases I (IC50: 73 microM) and II (IC50: 98 microM) without cleavable complexes. Furthermore, 1 and 2 showed the growth-inhibitory activity toward lung cancer cells LU 65 with IC50 values of 23 and 7 microM, respectively.     

Isolation, structure elucidation and activity of an unknown impurity of amphotericin B

An unknown impurity named amphotericin B (2) (AmB(2)) isolated from amphotericin B (AmB) bulk material was identified as (1S,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(3-amino-3,6-dideoxy-beta-D-mannopyranosyl)oxy]-1-methyloxy-3,5,6,9,11,17,37-heptahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid according to the IUPAC. The structure was elucidated by various 1D and 2D NMR techniques, mass spectrometry and by comparison with the NMR data of AmB. Its activity against Candida albicans was evaluated by comparison with AmB.     

Synthesis and antifungal activity of N-benzyl derivatives of amphotericin B

N-Benzyl derivatives of the polyene macrolide antibiotic amphotericin B were formed by reacting it with benzaldehydes and cyanoborohydride under reductive amination conditions. The physicochemical and biological properties of the resulting amphotericin B derivatives were studied. The N-benzyl derivatives of amphotericin B had high antifungal activity against a broad range of test cultures. Biological studies found that the acute toxicity of the amphotericin B derivatives was three times less than for the starting antibiotic. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 7, pp. 20–24, July, 2007.     

Penisporolides A and B, two new spiral lactones from the marine-derived fungus Penicillium sp

In our continued screening on bioactive constituents from marine-derived fungi, two novel compounds containing a rare spiral-lactone skeleton were isolated from lyophilized culture broth of the marine-derived fungus Penicillium sp. The structures of penisporolides A and B were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The relative stereochemistries of the compounds were assessed by analysis of NOESY data together with the comparison with data from previous literatures.     

Lecanorosides A and B,two new triterpene glycosides from the sea cucumber Actinopyga lecanora

Two new sulphated triterpene glycosides, lecanorosides A (1) and B (2), along with the known compounds holothurins A (3), A₁ (4), and B (5), were isolated from the sea cucumber Actinopyga lecanora. Their structures were deduced from extensive spectral analysis (NMR and MS) and chemical evidence. Glycosides 1 and 4 showed marginal in vitro cytotoxicity against two human tumour cell lines.     

Poriacosones A and B: two new lanostane triterpenoids from Poria cocos

Two new lanostane triterpenoids, poriacosones A (8) and B (9), together with eight known compounds were isolated from the sclerotia of Poria cocos (Schw.) Wolf (Polyporaceae), and identified by spectroscopic analysis, including IR, UV, CD, ESI-TOF-MS, HR-SIMS, 1D-, and 2D-NMR spectra. The structures of the new compounds were established as 3alpha,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (8) and 3beta,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (9).     

Poriacosones A and B: two new lanostane triterpenoids from Poria cocos

Two new lanostane triterpenoids, poriacosones A (8) and B (9), together with eight known compounds were isolated from the sclerotia of Poria cocos (Schw.) Wolf (Polyporaceae), and identified by spectroscopic analysis, including IR, UV, CD, ESI-TOF-MS, HR-SIMS, 1D-, and 2D-NMR spectra. The structures of the new compounds were established as 3alpha,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (8) and 3beta,16alpha-dihydroxy-24-oxolanost-7,9(11)-dien-21-oic acid (9).     

Seimisochromenes A and B: two new dihydroisochromenes from the endophytic fungus,Seimatosporium sp.

Two new dihydroisochromenes, named seimisochromenes A and B (1 and 2), were isolated from an endophytic fungus, Seimatosporium sp. The structures of seimisochromenes A and B have been determined from 1D (¹H and ¹³C NMR spectra) and 2D (COSY, HMQC, HMBC, and NOESY) NMR experiments.