KR101497145B1 - Novel compound and Antibiotic Composition comprising the same - Google Patents

Abstract

The present invention relates to a novel antibiotic activity compound and an antibiotic composition including the same and, more specifically, a compound, which inhibits lipogenesis of microorganisms, and uses thereof. To this end, provided is either a compound denoted by chemical formula 1 or pharmaceutically acceptable salt thereof. In addition, provided is a pharmaceutical composition for treating or preventing inflammation of pathogenic bacterium including the compound and pharmaceutically acceptable carriers thereof. One type of lead compounds which inhibits the growth of cells is found in the present invention.

Description

TECHNICAL FIELD The present invention relates to a novel antibiotic active compound and an antibiotic composition comprising the compound.

The present invention relates to novel antibiotic active compounds and antibiotic compositions comprising the compounds, and more particularly to compounds and their use for inhibiting microbial lipid synthesis.

The use of antibiotics to treat infectious diseases worldwide has increased significantly over the past several decades. In 1954, only two million pounds of antibiotics were produced in the United States. Today, the figure has exceeded 50 million pounds. According to the Centers for Disease Control (CDC), people consume 235 million antibiotics a year.

Pervasive abuse or overuse of antibiotics increases antibiotic resistance, contributing to serious public health problems. Antibiotic resistance occurs when the bacteria causing the infection are not rescued by the antibiotic used to stop the infection. Bacteria survive, multiply, and become more harmful. For example, Staphylococcus aureus is epidemiologically the main factor that infects a hospital that responds satisfactorily to vancomycin antibiotics. However, many Staphylococcus aureus strains have recently been shown to be resistant to vancomycin. Moreover, the mortality rate of some infectious diseases such as tuberculosis is increasing again due to bacterial resistance to antibiotics, in part.

Antibiotics are being used therapeutically to treat bacterial infections. Many types of antibiotics are currently used that are classified according to their mechanism of action. Known types of antibiotics include, for example, cell wall synthesis inhibitors, cell membrane inhibitors, protein synthesis inhibitors, and inhibitors that affect or bind DNA or RNA synthesis.

Cell wall synthesis inhibitors such as beta-lactam antibiotics generally inhibit some synthetic steps of bacterial peptidoglycan. Penicillin is generally effective against non-resistant streptococcus, gonococcus, and staphylococcus. Amoxicillin and ampicillin represent a broad spectrum of gram-negative bacteria. Cephalosporin is commonly used as a surgical precautions and penicillin replacement for gram-negative bacteria. Monobactam is generally useful for allergic subjects.

A number of antibiotics suitable for use in the treatment of bacterial-related diseases and disorders are described, for example, in The Physician's Desk Reference (PDR), Medical Economics Company (Montvale, NJ), (53rd Ed.), 1999; Mayo Medical Center Formulary, Unabridged Version, Mayo Clinic (Rochester, MN), January 1998; Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals, (11th Ed.), Merck & Co., Inc. (Rahway, NJ), 1989; University of Wisconsin Antimicrobial Use Guide, http: //www.medsch. wisc.edu/clinsci/5amcg/amcg.html: Introduction on the Use of the Antibiotics Guideline, of Specific Antibiotics Classes, Thomas Jefferson University, http://jeffiine.tju.edu/CWIS/OAC/antibiotics guide / intro.html Lt; / RTI >

FabD, which is Xoo0880, is one of Xoo's most important drug targeting enzymes. The FabD gene expresses the Malonyl-CoA-acyl carrier protein transacylase (MCAT) enzyme (EC 2.3.1.39). This protein transfers the malonyl moiety to the holo-acyl transfer protein, which forms the malonyl-ACP intermediate in bacterial type II fatty acid synthesis (Ruch, FE, and Vagelos, PR (1973). J Biol Chem 248 , 8086-94 .). This intermediate, malonyl-ACP, provides two carbons at the extended stage of fatty acid synthesis. Fatty acid synthesis (FAS) is essential for the survival of organisms (Magnuson, K., Jackowski, S., Rock, CO, and Cronan, JE, Jr. (1993) Microbiol Rev 57 , 522-42; SW, Zheng, J., Zhang, YM, and Rock (2005) Annu Rev Biochem 74 , 791-831). MCAT helps extend the length of the acyl chain to two carbon units. It has also been reported that MCAT is involved in polyketide biosynthesis that produces acyl-ACP thioester to produce one of the largest moieties of secondary metabolites such as tetracyclines and erythromycins (Keatinge-Clay, AT et al. 2003), Structure 11 , 147-54, Summers, RG et al. (1995), Biochemistry 34 , 9389-402). Thus, among the enzymes involved in the FAS process, MCAT is considered to be an essential enzyme in bacterial metabolism and is used as a potential drug target for the development of antibacterial drugs (Campbell, JW and Cronan, JE Jr. (2001). J Bacteriol, 183 , 5982-90 .; Miesel, L., J. Greene, and TA Black, 2003. Nature , 4 , 442-456; White, SW et al ., (2005) Annu Rev Biochem 74 , 791 -831.).

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made in view of the above-mentioned needs, and an object of the present invention is to provide a compound having antibiotic activity.

Another object of the present invention is to provide a composition comprising said compound.

In order to achieve the above object, the present invention provides a compound of the formula (I) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In one embodiment of the present invention, the compound inhibits malonyl-CoA: acyl carrier protein transactase (MCAT) activity, but is not limited thereto.

The present invention also provides a pharmaceutical composition for preventing or treating infection by a pathogenic bacterium comprising the compound of formula (I) of the present invention and a pharmaceutically acceptable carrier.

The present invention also provides a feed composition for preventing or treating infection by a pathogenic bacterium comprising the compound of formula (I) of the present invention and a pharmaceutically acceptable carrier.

The present invention also provides a pesticidal composition for preventing or treating infection comprising the compound of the formula (1) of the present invention and a pharmaceutically acceptable carrier.

In one embodiment of the present invention, the composition preferably has a microbial lipid synthesis inhibitory activity, but is not limited thereto.

In addition, the pharmaceutical composition of the present invention may further comprise pharmaceutically acceptable excipients, carriers, diluents and the like.

Examples of carriers that can be used in the present invention include macromolecules that are slowly metabolized, such as liposomes, polysaccharides, polylactic acid, polyglycolic acid, polymeric amino acids, and amino acid copolymers. Salts of inorganic acids such as, for example, hydrochloride, hydrobromide, phosphate and sulfate; Pharmaceutically acceptable salts such as salts of organic acids such as acetate, propionate, malonate and benzoate; Liquids such as water, saline, glycerol and ethanol, and auxiliary materials such as wetting agents, emulsifying agents or pH buffering substances may be used.

Pharmaceutically acceptable carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, 1991.

In addition, the composition may be formulated into a unit dosage form suitable for intra-body administration of a patient according to a conventional method in the pharmaceutical field, preferably a formulation useful for administration of a compound drug, Or intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual, vaginal or rectal But are not limited to, the parenteral route of administration.

Effective compound doses for bacterial therapy are from about 0.1 to about 50 mg or from 0.1 to 200 mg per kilogram of body weight per day of receptor body, more typically from about 0.1 to about 100 mg per kilogram of body weight per day of receptor body. The effective dose range of the pharmaceutically acceptable salts and prodrugs can be calculated based on the weight of the parent compound delivered. If the salt or prodrug exhibits activity on its own, the effective dose can be estimated as described above using the weight of the salt or prodrug, or by other means known to those skilled in the art.

For oral therapeutic administration, the active compounds may be used in the form of tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wipers etc. in combination with one or more excipients.

Tablets, troches, pills, capsules etc. may contain one or more of the following ingredients: binders such as microcrystalline cellulose, tragacanth gum, acacia, corn starch or gelatin; Excipients such as dicalcium phosphate, starch or lactose; Disintegrants such as corn starch, potato starch, alginic acid, Primogel and the like; Lubricants such as magnesium stearate or Sterotes; Lubricants such as colloidal silicon dioxide; Sweeteners such as sucrose, fructose, lactose, saccharin or aspartame; Flavorings such as peppermint, methyl salicylate, wintergreen oil or cherry flavor; And peptide antimicrobials such as Enbuviride (Fuzeon (TM)).

When the unit dosage form is a capsule, it may contain a liquid carrier such as vegetable oil or polyethylene glycol, in addition to materials of this type. Various other materials may be present as coatings or to modify the physical form of the solid unit dosage form.

The pharmaceutical composition of the present invention may be manufactured, packaged, or marketed as a formulation suitable for rectal administration. Such compositions may be, for example, in the form of suppositories, rectal preparations and solutions for rectal or colon cleansing. The pharmaceutical composition of the present invention may also be manufactured, packaged, or marketed as a formulation suitable for vaginal administration. Such compositions may be, for example, in the form of suppositories, implants or coated vaginal inserts such as tampons, detergents, solutions for vaginal cleaning.

The pharmaceutical composition of the present invention may be manufactured, packaged, or marketed as a formulation suitable for administration to the eye. For topical administration, the compounds of the present invention can be applied in pure form, i.e., as a liquid. Typically, however, the compound may be administered to the skin as a composition or formulation combined with a dermatologically acceptable carrier. Useful solid carriers include finely divided solids such as talc, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols, glycols, and mixtures of two or more thereof, wherein the compounds of the invention may optionally be dissolved or dispersed to an effective level using a non-toxic surfactant.

The pesticidal composition according to the present invention may further comprise other additional components such as an agriculturally acceptable support, carrier or filler.

As used herein, the term "support " refers to a natural or synthetic organic or inorganic material to which the active material is bound, in particular to facilitate its application to parts of plants. Thus, this support should be generally inert and agriculturally acceptable.

The retard can be solid or liquid. Examples of suitable supports include clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, water, alcohols, especially butanol, organic solvents, mineral oils and vegetable oils and their derivatives. Mixtures of the supports may also be used.

The pesticidal composition may also contain other additional ingredients. In particular, the pesticidal composition may further contain a surfactant. Surfactants may be ionic or nonionic emulsifiers, dispersants or wetting agents or mixtures of these surfactants. These include, for example, polyacrylates, lignosulfonates, phenol sulfonates or naphthalene sulfonates, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty amines, substituted phenols (especially alkyl phenols or aryl phenols) , Sulfosuccinic ester salts, taurine derivatives (especially alkyl taurates), phosphoric esters of polyoxyethylated alcohols or phenols, fatty acid esters of polyols, and derivatives of the above compounds having sulfate, sulfonate and phosphate functionalities. When the active substance and / or inert support is water-insoluble and the vector reagent for application is water, it is generally necessary that at least one surfactant is present. Preferably, the surfactant content may be from 5 to 40% by weight of the composition.

Additional components may also include, for example, protective colloids, tackifiers, thickeners, thixotropic agents, penetrants, stabilizers, sequestering agents. More generally, the active material may be combined with any solid or liquid additive according to conventional formulation techniques.

In general, the pesticidal composition according to the present invention may contain 0.05 to 99% (by weight), preferably 10 to 70% by weight of active substance.

The composition according to the present invention can be used as an aerosol dispenser, a capsule suspension, a chrysanthemum concentrate, a dustable powder, an emulsifiable concentrate, an oil-in-water emulsion, a water-in-oil emulsion, an encapsulated granule, a fine granule, a fluid concentrate for seed treatment, Oil-miscible liquids, oil-miscible liquids, pastes, plant rodlets, powders for dry seed treatment, etc.), gas generant products, granules, hotmelt concentrate, macrogranules, microgranules, oil dispersible powders, Suspension concentrates (fluid concentrates), ultra low volume (ulv) solutions, microvolume suspensions, water-dispersible granules or tablets, water-soluble granules or tablets, Water-dispersible powders for slurry treatment, water-soluble granules or tablets, soluble powders for seed treatment, and wettable powders.

These compositions include not only those compositions that are to be applied directly to plants or seeds to be treated using suitable equipment such as spraying or spraying equipment but also commercial concentrated compositions that must be diluted before application to crops.

The pesticidal composition of the present invention can be used for the therapeutic or prophylactic remedy of insects, as well as the therapeutic or prophylactic remedy of plant pathogenic bacteria of crops.

Accordingly, in accordance with a further aspect of the present invention there is provided a method for the treatment of seeds, leaves, stem application, or seed, plant and / or plant fruit or plant growth, (Eg, sand, rock wool, glass wool, expansive minerals such as pearlite, vermiculite, zeolite, expansive clay), plows, incineration rocks / tuff, synthetic organic matter (Eg, floats, compost, wood waste (eg coir, wood fiber / chip, bark)) and / or liquid substrates (eg float water systems, Nutrient Film Technique, A method of treating or prophylactically relieving insects as well as therapeutically or prophylactically rescue a phytopathogenic fungus of a crop, characterized in that it is applied through drench / drip application (irrigation) / RTI >

The expression "effective non-phytotoxic amount" refers to the amount of a composition according to the invention which is sufficient to rescue or eradicate pests and / or diseases present or present in the crop and which does not involve any significant plant toxic symptoms It means quantity. This amount can vary widely depending on the insect and disease to be eliminated or remedied, the type of crop, the climatic conditions and the compound contained in the composition according to the present invention. The amount may be determined by those skilled in the art and may be determined by systematic field trials.

The treatment methods according to the present invention may be useful for the treatment of seeds, seedlings or transplanted seedlings and plants or grafted plants as well as treatment of propagation material such as tubers or rhizomes. The treatment method may also be useful in the treatment of roots. The method of treatment according to the present invention may also be useful for treating surface areas of plants such as the body, stem or sack, leaf, flower and fruit of the relevant plant.

Plants that can be protected by the method of the present invention include cotton; maybe; Vine; Fruit or vegetable crops, seedlings, major crops such as Graminae sp. (Eg corn, grass or wheat, cereals such as rice, barley and lime), flowers, horticulture and forest crops; As well as genetically modified homologues of these crops.

In addition, the feed composition comprising the compound of the present invention or a salt thereof is used as feed for animals such as mammals, birds, reptiles, amphibians and fishes, preferably mammals. For example, the feed of the present invention is used as feed for pets such as dogs, cats, rats, cattle feed such as cows and pigs, feed for poultry such as chickens and turkeys, feed for breeding fish such as sea breams and defenses , Preferably used as feed for pets or feed for livestock.

The feed of the present invention can be prepared by appropriately compounding the compound of the present invention or a salt thereof in feed materials. Examples of feed materials include cereal grains, crude steel, vegetable oils, animal feedstuffs, other feedstuffs, and refined products.

Examples of cereals include maize, wheat, barley, oats, rye, brown rice, buckwheat, buckwheat, sorghum, blood, corn, soybeans and the like.

Examples of the crude steel include rice bran, defatted rice bran, wheat bran, horse meal, wheat, embryo, barley bran, screening, pellets, corn bran, and corn embryo.

Examples of vegetable oils include soybean meal, soybean meal, flaxseed meal, cottonseed meal, groundnut meal meal, safflower meal, palm oil palm, palm oil, fomarak, sunflower oil, rapeseed meal, cowpea oil and mustard oil.

Examples of raw animal feeds include fish meal (bean mill, imported wheat, hall mill, coastal wheat), fish shavings, meat meal, fish meal, blood meal, Casein, dry whey, and the like.

Examples of other feed materials include plant foliage (alfalfa, heukube, alfalfa leaf, and similar acacia powder), corn processing industry by-products (conglutin, wheat, conglutinfeed, constay prima etc.), starch products, (Cassava, bean curd, bean curd, bean curd, malt bean curd, alcohol bean curd, jangyu bean curd), agricultural production byproducts (citrus processing, tofu, coffee, cocoa, Krill, spirulina, chlorella, minerals, etc.).

Examples of the purified product include proteins (casein, albumin, etc.), amino acids, saccharides (starch, cellulose, sucrose, glucose, etc.), minerals and vitamins.

As can be seen from the present invention, the present inventors have found one kind of lead compound inhibiting bacterial cell growth in the range of ~ ug / ml.

Figure 1 shows the synthesis pathway of Type II bacterial fatty acids.
FIG. 2A is an SDS-PAGE photograph of purified fab D (Xoo0880), and 2b is a crystal photograph of 0.1 M CHES pH 9.0, 1.5 M NH ₄ SO ₄ , and 0.2 M NaCl.
Figure 3a shows the overall structure of XoMCAT, and 3b is a detail view of its active site.
FIG. 4 is a diagram illustrating a VLS experiment for searching for an antagonist drug for a specific target protein. FIG.
FIG. 5 is a diagram showing a process of analyzing bacterial cell growth inhibition with a selected compound derived from VLS. FIG.

The present invention will now be described in more detail by way of non-limiting examples. The following examples are provided for the purpose of illustrating the present invention, and the scope of the present invention is not construed as being limited by the following examples.

Preparation Example: Preparation of the compound of the present invention

The compounds used in the present invention were purchased from ChemBridge Corporation (16981 Via Tazon, Suite G, San Diego, CA, 92127, USA) in the United States and are available from the company's web site: http://www.chembridge.com/ .

Example 1: Xanthomona soryzae pv. oryzae Expression, purification, crystallization, crystal structure determination of XoMCAT derived from (Xoo)

Cloning

The FAD coding sequence of Xoo0880 was amplified by polymerase chain reaction using a bacterial cell (Xoo KACC10331 strain) as a template. Oligonucleotide primer sequences have been designed based on previously reported gene sequences (Lee, BM, et al. (2005) Nucleic Acids Res 33 , 577-86.). The forward and reverse primers were constructed as: 5'GGG GGG CAT ATG ACC GAA TCC ACT CTC GCC TTC A-3 and 5'-GGG GGG GGA TCC TCA GTG GCC CCA CGC GTC GAG A-3 'respectively. Nde I and Bam HI restriction sites are indicated in bold. The PCR amplicon was double-treated with Nde I and Bam HI and the tobacco etch virus (TEV) protease cleavage site and an additional residue of 6xHis were added to the Nde I site in the pET11a vector (Novagen) in order to facilitate the purification of the expressed protein Lt; RTI ID = 0.0 > pET11a < / RTI > vector (His-TEV-pET11a).

Over-expression and purification

A His-TEV-pET11a expression vector containing the coding sequence of Xoo0880 was introduced into E. coli BL21 (DE3). The cells were grown in Luria-Bertani medium containing 50 / / ml ampicillin at 37 째 C until OD ₆₀₀ reached 0.5. Protein expression was induced by adding 0.5 mM Isopropyl-beta-D-thiogalactopyranoside to the culture medium. After induction, the cells were incubated at the same temperature for an additional 16 hours. The cultured E. coli was collected by centrifugation (Vision VS24-SMTi V5006A rotor) at 277K for 20 minutes at 6,000 rpm. Then, the collected E. coli was resuspended in a temperature-lowered buffer for cell disruption A [25 mM Tris-HCl pH 7.5, 150 mM NaCl, 10 mM Imidazole] and sonicated in ice (Sonomasher, S & T Science, Korea) Lt; / RTI > Then, to obtain a cell extract, the disruption was centrifuged at 277K and 12,000 rpm for 30 minutes (Vision VS24-SMTi V508A rotor). Only 10% of the entire expressed Xoo0880 was water soluble (not shown). To use the affinity purification method, the supernatant containing the water-soluble fab D was loaded onto Ni-NTA resin (Novagen). The affinity purification was carried out at 4 캜 according to the manufacturer's protocol. The FabD protein with the 6xHis-tag was then eluted using a buffer A for disruption containing 200 mM imidazole and treated with TEV protease at 4 ° C overnight to remove the 6XHis-tag. The protein solution thus treated was dialyzed at 4 ° C. for 6 hours using buffer solution B [25 mM Tris-HCl pH 7.5, 15 mM NaCl], and further purified using a UNO 6 Q column (Bio-Rad). The purity of the purified protein was analyzed using SDS-PAGE (Fig. 2). The purified protein was concentrated to 7 mg ml ^-1 and used for crystallization.

Crystallization and X-ray diffraction data collection

Crystallization of XoMCAT was performed through the Hydra II e-drop (Matrix) automated pipetting system using several screening kits such as Crystal screen HT, Index HT, and Salt Rx HT (Hampton Research) high throughput (HT)] determination Screening started. Initially, a very thin needle-like crystals Wizard G-5 obtained in conditions (0.1 M CHES pH9.5, 1.25 M NH 4 SO 4, and 0.2 M NaCl), the modified conditions (0.1 M CHES pH9.0, 1.5 M NH ₄ SO ₄ , and 0.2 M NaCl). They were reproduced using the hanging drops method, and crystals were made for a week. The grown crystals were frozen at 100 K in liquid nitrogen after addition of antifreeze 20% ( v / v ) glycerol to the crystallization conditions. And used for data collection. Determination data was collected at 1.9 resolution using an ADSC Quantum 270 CCD detector at Beamline 17A of Photon Factory, Japan. Data sets were integrated and calculated using DENZO and SCALEPACK (Otwinowski, Z. and Minor, W. (1997) Methods Enzymol 276 , 307-326.). Through the auto-indexing process, the decision space group of P2 ₁ 2 ₁ 2 ₁ and the unit cell parameter a = 41.4, b = 74.6, c = 98.5 were deduced.

The crystal structure of XoMCAT and its active site residues are shown in Fig. The overall structure of XoMCAT consisted of two domains, a larger domain and a smaller domain, and folded reliably. The active site is located in the canyon between these domains. Larger domains were calculated from the DSSP program (Kabsch, W. and Sander, C. (1983). Biopolymers 22, 2577-637.) Water molecules of 12585 A ² had 14 alpha-helical structures with accessible surface area and 8 Beta-linear structure. Ser-94, the nucleophilic activating residue, is located in the sharp turn located between the alpha-helical structure and the beta-linear structure of the larger domain and the other active site residues Gln 13, Arg 119 and His 203 are located near the nucleophilic residue Located.

Example 2: Virtual library screening (VLS) process for target enzyme XoMCAT

Since Xoo0880 (XoMCAT) is one of the potential target genes for rice blight blight based on GlaxoSmithKline (GSK), it is antagonistic to the substrate binding site of XoMCAT enzyme through high efficiency (HT) virtual library screening (VLS, The drug lead compound was searched.

A computer simulation VLS was performed using a database of 18 million compounds in the ICM Molsoft modeling suite for drug screening. The substrate of each flexible structure present in the compound database found in the Lipinski formula of the VLS was docked to the substrate bonded pocket grid of XoMCAT using ICM and assigned a score reflecting the quality of the complex. In order to check the regeneration of each substrate binding result, they were simultaneously run in parallel three times. 1991 compounds with top scores were selected and their complexes were visualized (quantified) by coefficients such as shape complementarity, hydrogen bonding network and ligand flexibility. 500 compounds were obtained based on the final selection step for characterization through experimental analysis.

Example 3: Xoo, E. coli , And pseudomonas , Analysis of bacterial cell growth inhibition of the synthesized chemical compounds against each other and measurement of MIC (minimum inhibitory concentration) of each effective screened compound

3 ml of Xoo incubated overnight were inoculated into 100 ml of NB medium. The bacterial culture was incubated until an OD ₆₀₀ of 0.6 was reached. 150 [mu] l of bacterial culture was transferred to a 96 well ELISA plate containing 1 mM of screened compound retrieved from VLS. DMSO was used to dissolve the compound into a 30 mM concentration of the stock compound. The DMSO concentration was kept below 5% for all bacterial growth assays and the negative control used only the same concentration of DMSO. The plates were incubated at 28 with continuous shaking and absorbance was measured at constant intervals of 0, 3, 6, 9, and 12 hours at 600 nm. Compounds that inhibit more than 50% Xoo growth were selected to measure the MIC ₅₀ value of the compound.

MIC ₅₀  Method (microtiter plate-based anti-bacterial assay)

3 ml of Xoo incubated overnight were inoculated into 100 ml of NB medium. The bacterial culture was cultured to a cell density of 0.5 McFarland standards. The culture was diluted 10-fold and 150 [mu] l of the diluted culture broth was divided into sterilized 96-well clear flat bottom plates. Selected compounds with high bacterial cell growth inhibitory activity were serially diluted and added to 96-well plates at a concentration of 600 M to 9.5 M. A bacterial culture having only the same concentration of DMSO was used as a negative control. The plate incubated at 28 ℃, which was carried out the OD ₆₀₀ measured after 20 hours. Percent inhibition of bacterial growth was calculated by the equation below.

Inhibition Percent = 100 x (OD _nc - OD _tc ) / (OD _nc - OD _pc )

[OD _nc: the negative control OD _600, OD _tc: OD ₆₀₀ of the positive control (a known inhibitor): OD _600, OD _pc of the test compound.

MIC ₅₀ values were determined as the minimum compound concentration that inhibited 50% bacterial cell growth.

Table 1 is a table for MICs of lead compounds derived from bacterial cell growth inhibition assay.

ID rescue MIC ₅₀
 (쨉 g / mL)
6430298

13

Claims (8)

A compound of the formula (1):

[Chemical Formula 1]
The compound or its pharmaceutically acceptable salt thereof according to claim 1, wherein the compound inhibits malonyl-CoA: acyl carrier protein transactase (MCAT) activity. A pharmaceutical composition for preventing or treating infection by a pathogenic bacterium comprising the compound of claim 1 or 2 and a pharmaceutically acceptable carrier. [Claim 5] The pharmaceutical composition according to claim 3, wherein the composition is for preventing or treating infection by a pathogenic microorganism having lipid-lowering activity. A feed composition for the prevention or treatment of infection by a pathogenic bacterium comprising the compound of claim 1 or 2 and a pharmaceutically acceptable carrier. 6. The feed composition according to claim 5, wherein the composition is a microbial lipid synthesis inhibiting activity. A pesticidal composition for preventing or treating an infection comprising the compound of claim 1 or 2 and an agrochemically acceptable carrier. An antimicrobial composition comprising the compound of claim 1 or 2 as an active ingredient.

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