43 results about "Peptide deformylase" patented technology

This invention provides a method for inhibiting the growth of a microorganism that expresses Peptide Deformylase by contacting the microorganism with an effective amount of the compound described herein. This method inhibits the growth of gram-positive and gram-negative microorganism, e.g., S. aureus, S. epidermidis, K. pneumoniae, E. aerogenes, E. cloacae, M. catarrhalis, E. coli, E. faecalis, H. influenzae and P. aeruginosa. This method can be practiced in vitro, ex vivo and in vivo. Further provided is a method for alleviating the symptoms of an infection by a Peptide Deformylase expressing microorganism in a subject by administering or delivering to the subject an effective amount of the compound described above.

The invention provides a peptide deformylase inhibitor containing 4-methylene pyrrolidine and relates to a peptide deformylase inhibitor. The peptide deformylase inhibitor has the structural formula shown in the specification, and in the formula, R1 is alkyl, R2 is H or alkyl, and R3 is alkyl or aryl or heterocycle. The peptide deformylase inhibitor can inhibit bacterial to synthesize protein so as to kill the bacterial, has small chance of drug resistance generation, is safe for a human body and can kill strains having antibiotic resistance, such as methicillin-resistant staphylococcus aureus (MRSA) and penicillin resistant streptococcus pneumoniae (PRSP).

The present invention provides methods and compositions for increasing the susceptibility of PDF inhibitors against Gram-negative organisms by using efflux pump inhibitors.

The invention discloses a novel peptide deformylase inhibitor containing spiro-three-membered ring and spiro-five-membered ring types. The novel peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types has antibacterial activity and anti-tumor activity. The peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types can serve as a novel antibacterial agent, by inhibiting the activity of peptide deformylase needed in synthesis of bacterium proteins, the novel peptide deformylase inhibitor is effective on multiple antibiotic resistant Gram-positive bacterium strains, the synthesis process of proteins of human bodies is not affected, and accordingly bacteria are killed selectively. The peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types can further serve as a novel anti-cancer drug; by inhibiting peptide deformylase in mitochondria of cancer cells, energy balance of the cells can be affected, accordingly mitochondrial membranes are depolarized, ATP is used up, and cell apoptosis is promoted; and the novel peptide deformylase inhibitor has good inhibiting activity to multiple cancer cell bacterial strains such as colorectal cancer cell bacterial strains, lung cancer cell bacterial strains, gastric cancer cell bacterial strains and liver cancer cell bacterial strains at the low concentration.

A macrocyclic peptide deformylase (PDF) inhibitor comprising a peptide or peptide mimetic having three residues, P1′, P2′, and P3′, wherein P2′ connects P1′ and P3′,wherein P1′ and P3′ each have a side chain, and wherein the side chains on P1′ and P3′ are crosslinked to form the macrocyclic PDF inhibitor. The side chains of P1′ and P3′ interact with the PDF active site, and preferably, P2′ has a side chain that interacts with a solvent. Also provided are methods of inhibiting the growth of a bacterium, the methods comprising contacting the bacterium with an anti-bacterial effective amount of the inventive macrocyclic PDF inhibitor. Additionally, a method of treating a bacterial infection in a subject comprising administering an effective amount of a macrocyclic PDF inhibitor to a subject in need of treatment. Additionally, methods of preparing macrocyclic PDF inhibitors comprising a) choosing an acyclic base molecule, having at least some PDF inhibitory activity, the acyclic base molecule having a first residue having a first side chain that interacts with the PDF active site and a second residue having a second that interacts with the PDF active site; and b) crosslinking the first side chain and the second side chain to form a macrocyclic PDF inhibitor.

The instant invention provides novel benzofuran-4,5-diones and pharmaceutical compositions thereof useful for inhibiting PDF and for treating proliferative and infectious diseases. Compounds may be selective for eukaryotic (e.g., human) PDF or prokaryotic PDF.

The present invention provides methods and compositions for increasing the susceptibility of PDF inhibitors against Gram-negative organisms by using efflux pump inhibitors.

The invention discloses novel peptide deformylase inhibitors containing spiro three-membered rings or spiro five-membered rings, and the inhibitors have antimicrobial activity and antineoplastic activity. The peptide deformylase inhibitors containing spiro rings such as the spiro three-membered rings or the spiro five-membered rings provided in the invention can be taken as a class of novel antibacterial agents, by inhibiting activity of peptide deformylase required in synthesis of bacterial proteins, the inhibitors have effects on gram-positive bacterium strains which have drug resistance to a plurality of antibiotics, and have no influences on synthetic processes of human proteins, thus the bacteria are selectively killed; and the peptide deformylase inhibitors containing the spiro rings such as the spiro three-membered rings or the spiro five-membered rings provided in the invention can also be taken as a class of novel anti-cancer drugs, by inhibiting peptide deformylase in mitochondria of cancer cells, the inhibitors can have influences on energy balance of the cells, thus mitochondrial membranes are depolarized, ATP is depleted and apoptosis is promoted, and the inhibitors have relatively-good inhibition activity on a plurality of cancer cell bacterial strains such as colorectal cancer cell bacterial strains, lung cancer cell bacterial strains, stomach cancer cell bacterial strains and liver cancer cell bacterial strains under relatively-low concentrations.

The invention discloses a heterocyclic peptide deformylase inhibitor and a preparation method and application thereof. The structure of the inhibitor is shown in formula (I), wherein A is a five-membered nitrogen-containing aromatic heterocycle, X, Y and Z are C, O, S or N independently, and R is a single substituent, multiple substituents or forms a ring with A. The peptide deformylase inhibitordisclosed by the invention is novel in structure, good in activity and low in toxicity, has obvious inhibition effects on gram-positive bacteria and gram-negative bacteria, and even has good inhibition effects on bacteria with multiple drug resistance; and meanwhile, the compound has remarkable inhibition effect on tumor cells such as colorectal cancer, lung cancer and osteosarcoma, can inhibit proliferation of the tumor cells, and can be prepared into antibacterial drugs or antitumor drugs for application.

A macrocyclic peptide deformylase (PDF) inhibitor comprising a peptide or peptide mimetic having three residues, P1′, P2′, and P3′, wherein P2′ connects P1′ and P3′, wherein P1′ and P3′ each have a side chain, and wherein the side chains on P1′ and P3′ are crosslinked to form the macrocyclic PDF inhibitor. The side chains of P1′ and P3′ interact with the PDF active site, and preferably, P2′ has a side chain that interacts with a solvent. Also provided are methods of inhibiting the growth of a bacterium, the methods comprising contacting the bacterium with an anti-bacterial effective amount of the inventive macrocyclic PDF inhibitor. Additionally, a method of treating a bacterial infection in a subject comprising administering an effective amount of a macrocyclic PDF inhibitor to a subject in need of treatment. Additionally, methods of preparing macrocyclic PDF inhibitors comprising a) choosing an acyclic base molecule, having at least some PDF inhibitory activity, the acyclic base molecule having a first residue having a first side chain that interacts with the PDF active site and a second residue having a second that interacts with the PDF active site; and b) crosslinking the first side chain and the second side chain to form a macrocyclic PDF inhibitor.

The present invention relates to the novel antibacterial compounds having potent antibacterial activity as inhibitors of peptide deformylase. This invention further relates to pharmaceutically acceptable salts thereof, to processes for their preparation, and to pharmaceutical compositions containing them as an active ingredient.

The invention discloses a formylation gene cassette knockout mutant of Escherichia coli DH5alpha and a construction method thereof. The construction method utilizes a lambdaRed homologous recombination technology to simultaneously perform gene knockout on the gene fmt encoding the methionine-tRNA transformylase on the Escherichia coli E.coli DH5alpha chromosome and the gene def encoding the peptide deformylase, and PCR product electrophoresis and sequencing identification confirm that the obtained strain is a knockout mutant. The construction method of the invention is simple, an expression frame of other proteins on the genome is not changed, and the knock-in replacement of the chloramphenicol resistance gene facilitates the preservation of the strain and is beneficial for subsequent application. The constructed formylation gene knockout mutant of Escherichia coli DH5alpha completely eliminates the influence of PDF from the gene level, and can be used as the original material for studying the physiological process of formylation and deformylation, and the samples are provided for proteomics and metabolomics.

The present invention relates to the novel antibacterial compounds having potent antibacterial activity as inhibitors of peptide deformylase. This invention further relates to pharmaceutically acceptable salts thereof, to processes for their preparation, and to pharmaceutical compositions containing them as an active ingredient.

The present invention is directed to certain {2-(alkyl)-3-[2-(5-fluoro-4-pyrimidinyl)hydrazino]-3-oxopropyl}hydroxyformamide derivatives, compositions containing them, the use of such compounds in the inhibition of bacterial peptide deformylase (PDF) activity, and in the treatment of bacterial infections. Specifically, the invention is directed to compounds of formula (I), wherein R1, R2 and R3 are defined herein and to pharmaceutically acceptable salts thereof. The compounds of this invention are bacterial peptide deformylase inhibitors and can be useful in the treatment of bacterial infections.

The invention relates to a method of identifying herbicides and to the use of inhibitors of plant peptide deformylase as broad spectrum herbicides.

The invention relates to alpha-aryl alanine compounds and a preparation method thereof. Alpha-aryl alanine compounds shown as general formulas (I) and (II) are racemate, wherein R1, R2 and R3 shown as general formulas (I) and (II) are expressed as hydrogen atoms, halogen atoms, hydroxyl, substituted or non-substituted alkyl, alkenyl, alkoxy, aryl, aryl alkyl, alkyl or aryl acyl; R4 is expressed as the hydrogen atoms, formoxyl, acetyl, trifluoro-acetyl, benzoyl, phthaloyl, triphenylmethyl, carbobenzoxy, trimethyl silicon carbethoxy, benzyl, 2,4-dimethoxy benzyl, p-methoxy benzyl and diphenyl phosphoryl; and R5 is expressed as the hydrogen atoms, methyl or ethyl. The invention has the advantages that a novel method for preparing the alpha-aryl alanine compounds, which is low in cost of raw materials, mild in reaction conditions and high in yield is provided, and the alpha-aryl alanine compounds can be used as a synthetic intermediate of a peptide deformylase enzyme (PDF) inhibitor.

This invention provides compounds and methods for using them to inhibit the growth of microorganism that expresses Peptide Deformylase, the compounds having the general formula:

The present invention relates to the novel antibacterial compounds having potent antibacterial activity as inhibitors of peptide deformylase. This invention further relates to pharmaceutically acceptable salts thereof, to processes for their preparation, and to pharmaceutical compositions containing them as an active ingredient.

The present invention relates to the design of the Antisense-oligonucleotide complementary to the specific region of peptide deformylase gene from Mycobacterium tuberculosis. The use of this Antisense-oligonucleotide on mycobacterial culture inhibits the production of the peptide deformylase enzyme by hybridizing within the region, which is found to be responsible for maintaining stability as well as retaining the functionality of the enzyme and thus in turn affecting the growth of the cells. This invention also establishes the essentiality of the peptide deformylase enzyme in mycobacteria and claims it as a drug target in this microorganism.

The instant invention provides novel benzofuran-4,5-diones and pharmaceutical compositions thereof useful for inhibiting PDF and for treating proliferative and infectious diseases. Compounds may be selective for eukaryotic (e.g., human) PDF or prokaryotic PDF.

The invention belongs to the technical field of antibacterial and anti-cancer drugs, and particularly relates to an aryl ketone peptide deformylase inhibitor and application thereof in antibacterial and anti-tumor aspects. The aryl ketone peptide deformylase inhibitor is novel in structure, better in activity and small in toxicity; on one hand, the aryl ketone peptide deformylase inhibitor has better antibacterial activity, especially on gram-negative bacteria (such as acinetobacter baumannii and the like), and can be applied to preparation of drugs for inhibiting pathogenic microorganisms; and on the other hand, the inhibitor has good anti-tumor activity, shows good inhibitory activity on various tumor cells (such as colorectal cancer, breast cancer, lung cancer and osteosarcoma), and can be applied to preparation of anti-tumor drugs. The aryl ketone peptide deformylase inhibitor has good application prospects in the antibacterial and anti-tumor aspects.

The invention discloses a novel peptide deformylase inhibitor containing spiro-three-membered ring and spiro-five-membered ring types. The novel peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types has antibacterial activity and anti-tumor activity. The peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types can serve as a novel antibacterial agent, by inhibiting the activity of peptide deformylase needed in synthesis of bacterium proteins, the novel peptide deformylase inhibitor is effective on multiple antibiotic resistant Gram-positive bacterium strains, the synthesis process of proteins of human bodies is not affected, and accordingly bacteria are killed selectively. The peptide deformylase inhibitor containing the spiro-three-membered ring and spiro-five-membered ring types can further serve as a novel anti-cancer drug; by inhibiting peptide deformylase in mitochondria of cancer cells, energy balance of the cells can be affected, accordingly mitochondrial membranes are depolarized, ATP is used up, and cell apoptosis is promoted; and the novel peptide deformylase inhibitor has good inhibiting activity to multiple cancer cell bacterial strains such as colorectal cancer cell bacterial strains, lung cancer cell bacterial strains, gastric cancer cell bacterial strains and liver cancer cell bacterial strains at the low concentration.

Benzimidazole compounds of the general formula (I) and pharmaceutically acceptable salts or esters thereof are peptide deformylase inhibitors useful in the treatment or prevention of infections and other diseases in which peptide deformylases are involved, especially in the treatment of bacterial and parasitic infections, for example infections fully or partly caused by microorganisms belonging to Staphylococcus, Enterococcus, Streptococcus, Haemophilus, Moraxella, Escherichia, Mycobacterium, Mycoplasma, Pseudomonas, Chlamydia, Rickettsia, Klebsiella, Shigella, Salmonella, Bordetella, Clostridium, helicobacter, Campylobacter, Legionella, or Neisseria.

The invention belongs to the technical field of biological medicines, and particularly relates to an imidazole peptide deformylase inhibitor with an anti-tumor effect. In order to research and develop a novel small molecule compound targeting HsPDF, the invention discloses an imidazole peptide deformylase inhibitor with an anti-tumor effect, and the imidazole peptide deformylase inhibitor is novel in structure, better in activity and small in toxicity, has better anti-tumor activity, and can be used for preparing an anti-tumor drug. The compound has good inhibitory activity on various tumor cells (such as colorectal cancer cells, breast cancer cells and lung cancer cells), can be applied to preparation of anti-tumor drugs or drugs for inhibiting tumor cell proliferation, and has good application prospects in the anti-tumor aspect.

Disclosed are the anti-bacterial activity and the anti-tumor activity of a class of new spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, are effective against many antibiotic-resistant Gram-positive strains by inhibiting the activity of the peptide deformylase required in the synthesis of bacterial proteins, and do not affect the synthetic process of the main proteins of the human body, thus selectively killing bacteria. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, can affect the energy balance of the cancer cells through inhibiting the peptide deformylase of the mitochondria in the cells, so that the mitochondrial membrane is depolarized, ATP is exhausted and cell apoptosis is promoted, and has good inhibitory activities on many cancer cell strains such as colorectal cancer, leukemia, lung cancer, gastric cancer, cervical cancer, breast cancer, prostatic cancer, liver cancer and osteosarcoma at relatively lower concentrations.

Isoxazole compounds of formula (I) and pharmaceutically acceptable salts or esters thereof are peptide deformylase inhibitors useful in the treatment or prevention of infections and other disease in which peptide deformylases are involved, especially in the treatment of bacterial and parasitic infections, for example infections fully or partly caused by microorganisms belonging to Staphylococcus, Enterococcus, Streptococcus, Haemophilus, Moraxella, Escherichia, Mycobacterium, Mycoplasma, Pseudomonas, Chlamydia, Rickettsia, Klebsiella, Shigella, Salmonella, Bordetella, Clostridium, Helicobacter, Campylobacter, Legionella or Neisseria.

Disclosed are the anti-bacterial activity and the anti-tumor activity of a class of new spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, are effective against many antibiotic-resistant Gram-positive strains by inhibiting the activity of the peptide deformylase required in the synthesis of bacterial proteins, and do not affect the synthetic process of the main proteins of the human body, thus selectively killing bacteria. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, can affect the energy balance of the cancer cells through inhibiting the peptide deformylase of the mitochondria in the cells, so that the mitochondrial membrane is depolarized, ATP is exhausted and cell apoptosis is promoted, and has good inhibitory activities on many cancer cell strains such as colorectal cancer, leukemia, lung cancer, gastric cancer, cervical cancer, breast cancer, prostatic cancer, liver cancer and osteosarcoma at relatively lower concentrations. The structure of exemplary invention spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitors are represented by one or more of:

The invention discloses antibacterial activities and antineoplastic activities of novel spiro three-membered ring and spiro five-membered ring containing peptide deformylase inhibitors. The spiro three-membered ring and spiro five-membered ring containing peptide deformylase inhibitors can be used as a novel antibacterial agent, are effective for multiple antibiotic-resistant Gram-positive bacteria strains by inhibiting activities of the peptide deformylase required in bacterial protein synthesis, and do not influence the protein synthesis process of the human body, thereby selectively killing the bacteria. The spiro three-membered ring and spiro five-membered ring containing peptide deformylase inhibitors can also be used as a novel anticancer drug, and can influence the energy balance of cells by inhibiting the peptide deformylase in cancer cell mitochondria; and therefore, mitochondrial membranes are depolarized, ATP is exhausted, cell apoptosis is promoted, so that the peptide deformylase inhibitors have favorable inhibition activities for multiple cancer cell strains, such as colorectal cancer, lung cancer, stomach cancer and liver cancer.