Pradip R. Das

A new fungal metabolite, Sch 202596, with inhibitory activity in the galanin receptor GALR1 assay

Abstract A novel spirocoumaranone, Sch 202596 ( 1 ), was isolated from the fermentation broth of Aspergillus sp. The isolation, structure elucidation and stereochemistry of 1 are described.

A novel microbial metabolite, activator of low density lipoprotein receptor promoter

The organic extract of the fermentation broth of a Micromonospora microorganism was found to contain SCH 351448 (1), the monosodium salt of a macrocyclic dilactone containing two identical diacids. The structure and relative stereochemistry were established by single-crystal X-ray analysis. SCH 351448 is a novel ionophoric compound and is a weak activator of low density lipoprotein receptor (LDL-R) promoter with an IC50 of 25 μM.

A depsipeptide fungal metabolite inhibitor of cholesteryl ester transfer protein

The organic extract of the fermentation broth of a fungus was found to contain a depsipeptide SCH 58149 (1), containing three amino acids and a beta-hydroxy acid, by spectroscopic studies. The amino acids were phenyl alanine, alanine and leucine and the beta-hydroxy acid is 3-hydroxy-4-methyl octanoic acid. SCH 58149 exhibited weak activity against cholesterol ester transfer protein (CETP) with an IC50 of 50 microM.

Two antiviral compounds from the plant Stylogne cauliflora as inhibitors of HCV NS3 protease

The 70% aq methanolic extract of the Peruvian plant Stylogne cauliflora was found to contain two novel oligophenolic compounds SCH 644343 (1) and SCH 644342 (2), which were identified as inhibitors of HCV NS3 protease. The structure of 1 and 2 was established based on high-resolution NMR studies. Compound 1 inhibited HCV NS3 protease with an IC(50) of 0.3 microM, while compound 2 showed an IC(50) of 0.8 microM.

Two selective novel triterpene glycosides from sea cucumber, Telenata Ananas: inhibitors of chemokine receptor-5.

The aqueous methanolic extract of a sea cucumber was found to contain two triterpene glycosides 1 and 2. The structures of 1 and 2 were established based on high-resolution NMR studies. Compounds 1 and 2 exhibited inhibitory activity (K(i)) of 30 and 5microM, respectively, in a chemokine receptor subtype 5 (CCR5) assay. Both compounds did not show any significant inhibition in a CXCR2 assay at 50microM, suggesting their selectivity for the CCR5 receptor.

Sch 65676: A novel fungal metabolite with the inhibitory activity against the cytomegalovirus protease

A new secondary metabolite, Sch 65676 (1), was isolated from the fermentation broth of a fungal culture. The structure of 1 was elucidated based on comprehensive NMR studies including COSY, NOE and HMBC experiments. Compound 1 displays inhibitory activity against the cytomegalovirus (CMV) protease.

Sch 53823 and Sch 53825, novel fungal metabolites with phospholipase D inhibitory activity

Abstract Two novel phospholipase D (PLD) inhibitors, Sch 53823 (1) and Sch 53825 (2), were isolated from a fungal culture. The acetylated derivatives, Sch 53827 (3) and Sch 53829 (4), were prepared for the purpose of structure determination. The extensive NMR studies of 3 and 4 including DEPT, COSY, NOESY, HETCOR, and selective INEPT experiments permitted the establishment of their structures, as well as relative stereochemistries. Among these compounds, 3 exhibited the most potent inhibitory activity in the phospholipase D assay with the IC50 = 17 μM.

Chemical modifications and structure activity studies of ziracin and related everninomicin antibiotics.

Chemical modifications of eveminomicin antibiotics, particularly ziracin (1), were carried out to study the SARs as well as the chemical properties of this class of compounds. Use of allyl ether group for protection and selective deprotection of phenolic groups provided access to a variety of novel analogs of the title compounds, some of which exhibited the same high in vitro potency as the parent compounds.

A new potent antifungal agent from Actinoplanes sp

Abstract A novel antifungal agent, Sch 56036 ( 1 ), was isolated from the fermentation culture broth of an Actinoplanes sp. Structure elucidation of 1 was accomplished by the analysis of spectroscopic data. Compound 1 was identified as a new polycyclic xanthone. Biological evaluation of 1 indicated that the compound possesses broad spectrum antifungal activity against various yeasts and dermatophytes with geometric mean MIC values ranging from 0.017∼0.031 μg/mL, respectively.

DETERMINATION OF THE ABSOLUTE STEREOCHEMISTRY AT THE C16 ORTHOESTER OF EVERNINOMICIN ANTIBIOTICS; A NOVEL ACID-CATALYZED ISOMERIZATION OF ORTHOESTERS

Abstract The absolute stereochemistry at C16 orthoester center of Ziracin ( 1 ) was unequivocally established via a novel acid-catalyzed orthoester isomerization. Structures of the resulting isomers 2 and 3 were determined by chemical degradation and extensive spectroscopic analyses. This novel isomerization was successfully extended to other related everninomicins ( 11–13 ), thus completing the entire structural assignment of everninomicin antibiotics.