Cytotoxic depsipeptides

a cytotoxic and peptide technology, applied in the field of new depsipeptide compounds, can solve the problems of cancer being the leading cause of death in animals and humans

Inactive Publication Date: 2008-09-18
INST BIOMAR SA
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cancer is a leading cause of death in animals and humans.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Cytotoxic depsipeptides
  • Cytotoxic depsipeptides
  • Cytotoxic depsipeptides

Examples

Experimental program
Comparison scheme
Effect test

example 1

Production of IB-01211

[0080] Inoculum development: a frozen culture of ES7-008 or a well grown slant culture (5% vol.) is used to seed 100 ml of a seed medium, as described in Table 1, that it is contained in a 250 ml shake flask. The flask is incubated during 48 h. A 2 l Erlenmeyer flask with 500 ml of the same medium is seeded with 10% vol. of the first stage inoculum. The flask is incubated during 48 h.

[0081] Fermentation step: 50 l of production medium, as described in Table 1, contained in a 75 l fermentation tank are seeded with 2.5 l of second stage inoculum. The fermentation is carried out during 96 h with 400 rpm agitation and an air flow of 0.5V / V.M.

example 2

Isolation of IB-01211

[0082] 8.5 liters of whole harvested broth were filtrated to separate the biomass and other solids. The mycelia cake was extracted twice with a mixture solvent (2.4 l) of CHCl3:CH3OH:H2O (2:1:1). The activity was concentrated in the lower layer. The organic solvent was concentrated and evaporated to dryness in vacuo to yield 4.8 g of crude extract.

[0083] The extract was applied to a silica gel VFC (vacuum flash chromatography) system, using a mixture of n-hexane-EtOAc and EtOAc-MeOH as eluting solvents. The fractions with antitumour activity, containing IB-01211 (900 mg) were eluted with EtOAc-MeOH 1:1, EtOAc-MeOH 1:3 and methanol. The active fractions were chromatographied twice with a silica gel column using CHCl3-MeOH and EtOAc-MeOH mixtures as eluting solvents. The cytotoxic activity was detected in fractions eluted with CHCl3-MeOH 96:4 in the first chromatography (200 mg of pure compound IB-01211) and in fractions eluted with EtOAc-MeOH 85:15-8:2 in the s...

example 3

Biological in vitro Activity Bioassays for Antitumour Screening

[0085] The finality of these assays is to interrupt the growth of an “in vitro” tumour cell culture by means a continued exhibition of the cells to the sample to be testing. The following human cell lines were used:

CELL LINESNameNo ATCCTissueCharacteristicsK-562CCL-243leukemiaerythroleukemia (pleural effusion)A-549CCL-185lunglung carcinoma “NSCL”SK-MEL-28HTB-72melanomamalignant melanomaHT-29HTB-38coloncolon adenocarcinomaDU-145HTB-81prostateprostate carcinoma, not androgenreceptorsLNCaPCRL-1740prostateprostate adenocarcinoma, with androgenreceptorsPC-3CRL-1435prostateprostate adenocarcinomaBT-474HTB-20breastbreast adenocarcinomaMX-1breastbreast adenocarcinoma,Hs746tHTB-135gastricstomach carcinomaSK-HEP-1HTB-52liverliver adenocarcinomaSK-OV-3HTB-77ovaryovary adenocarcinoma (malignant ascites)PANC-1CRL-1469pancreaspancreatic epitheloid carcinoma5637HTB-9bladderbladder carcinomaFADUHTB-43pharynxsquamous cell carcinoma786...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
pharmaceutical compositionaaaaaaaaaa
UV spectrumaaaaaaaaaa
spectrumaaaaaaaaaa
Login to view more

Abstract

Compounds of general formula (1) wherein R1, R2, R3 are as defined and R4 groups are each independently selected from NR2, O and S; are of use in treatment of cancers.

Description

FIELD OF THE INVENTION [0001] The present invention relates to new depsipeptide compounds, pharmaceutical compositions containing them and their use as antitumoural agents. BACKGROUND OF THE INVENTION [0002] Several cyclic peptides obtained from marine organisms have been disclosed (see for example Rudi A. et al., J. Nat. Prod., 2003, 66, 575-577: “Didmolamide A and B, two new cyclic hexapeptides from the marine Ascidian Didemnum molle”). [0003] JP 11180997 discloses an antitumour compound of formula which is obtained from Streptomyces nobilis. Its IC50 in Hela S3 cells is 14 nM. [0004] Cancer is a leading cause of death in animals and humans. Several efforts have been and are still being undertaken in order to obtain an antitumour agent active and safe to be administered to patients suffering from a cancer. The problem to be solved by the present invention is to provide compounds that are useful in the treatment of cancer. SUMMARY OF THE INVENTION [0005] The present invention is ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/429C07D498/22C12N1/20C12P17/00C07K5/083
CPCC07K5/0808Y10S530/825A61P35/00C07K11/00C07K5/0821
Inventor ROMERO, FRANCISCOMALET, LEYRECANEDO, LIBRADA MARIACUEVAS, CARMENREYES, JOSE FERNANDO
Owner INST BIOMAR SA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap