Vinod R. Hegde

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.

COMPLESTATIN AND CHLOROPEPTIN I, CONDENSED AROMATIC PEPTIDES FROM TWO STRAINS OF STREPTOMYCETES

Abstract The mycelial extract of the fermentation broths from two strains of streptomycetes were found to contain complestatin and a mixture of complestatin and chloropeptin I, respectively. Extraction and detection of these compounds using identical procedures is evidence that complestatin and chloropeptin I are indeed natural products.

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.

D4 dopamine receptor-selective compounds from the Chinese plant Phoebe chekiangensis

5-Hydroxy-indoline ( 1 ), tyramine ( 2 ), N-norarmepavine ( 3 ), and a novel glycosylated tetrahydroisoquinoline analog SCH 71450 ( 4 ) were all isolated from a methanol extract from the fruit of the Chinese plant Phoebe chekiangensis based on their activity in displacing D 4 dopaminergic receptor ligand binding. These compounds and related natural products were evaluated for D 4 receptor selectivity relative to D 2 receptor binding displacement. Compounds 1 and 4 exhibited better D 4 selectivity than standard dopaminergic antagonists including the clinically useful compound clozapine. GppNHp shifts in displacement curves indicated that compound 1 is an agonist while compound 4 is an antagonist.

New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme.

The 70% aqueous methanolic extract of the Chinese plant Aristolochia manshuriensis was found to contain two novel substituted phenanthrene compounds, SCH 546909 (1), and another phenanthrene glycoside (2). The structures of 1 and 2 were established based on NMR studies. They were identified as inhibitors of the CDK2 enzyme. Compound 1 was found to be a potent inhibitor of the CDK2 enzyme with an IC50 of 140 nM, whereas compound 2 was found to be less active with an IC50 of >10 microM.

Novel thiodiketopiperazine fungal metabolites as epidermal growth factor receptor antagonists

Abstract The organic extract of the fermentation broth of an unidentified fungus was found to contain three epidermal growth factor (EGF) receptor anagonists: SCH 64874 ( 1 ), SCH 64875 ( 2 ), SCH 64877 ( 3 ). These compounds belong to a family of thiodiketopiperazine derivatives and are esters of an eight carbon aliphatic acid, 2,4- dimethyl-3-hydroxyhexanoic acid and a thiodiketopiperazine, aranotin. They exhibited potent EGF receptor antagonist activity. The IC 50 in EGF receptor assays for compounds 1 , 2 and 3 are 1.0, 1.0 and 1.25 μg/ml, respectively.

Semi-synthetic aristolactams--inhibitors of CDK2 enzyme.

Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure-activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature.

A new isochromanequinone antibiotic, SCH 38519, with a novel sugar linkage

Abstract The structure and absolute stereochemistry of antibiotic Sch 38519 have been determined from 2D 1 H- and 13 C-NMR data and by a single-crystal X -ray analysis of its hydrochloride salt. This antibiotic contains an aminosugar linked in a novel manner through C 1′ and C 5′ to the aromatic ring of an isochromanequinone.