3947-65-7

Basic information

• Product Name: (1'R,3'S,3S,5R,6R)-5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL
• Synonyms: (1'R,3'S,3S,5R,6R)-5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL;5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL;NEAMINE;U-5214;2-deoxy-4-o-(2,6-diamino-2,6-dideoxy-alpha-d-glucopyranosyl)-d-streptamin;dekamycinv;neamin;nebramycinx
• CAS NO: 3947-65-7
• Molecular Formula: C₁₂H₂₆N₄O₆
• Molecular Weight: 322.36
• Mol File: 3947-65-7.mol
• Article Data: 13

Chemical Properties

• Melting Point: 225.5°C (rough estimate)
• Boiling Point: 460.98°C (rough estimate)
• Flash Point: 303.3°C
• Appearance: /
• Density: 1.1885 (rough estimate)
• Vapor Pressure: 9.19E-16mmHg at 25°C
• Refractive Index: 1.6120 (estimate)
• Storage Temp.: Hygroscopic, Refrigerator, Under inert atmosphere
• Solubility: Aqueous Acid (Slightly), Methanol (Slightly, Heated), Water (Slightly)
• PKA: 13.24±0.70(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: (1'R,3'S,3S,5R,6R)-5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL(CAS DataBase Reference)
• NIST Chemistry Reference: (1'R,3'S,3S,5R,6R)-5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL(3947-65-7)
• EPA Substance Registry System: (1'R,3'S,3S,5R,6R)-5-AMINO-2-AMINOMETHYL-6-(4,6-DIAMINO-2,3-DIHYDROXY-CYCLOHEXYLOXY)-TETRAHYDRO-PYRAN-3,4-DIOL(3947-65-7)

Safety Data

• Hazardous Substances Data: 3947-65-7(Hazardous Substances Data)

Usage

Definition

ChEBI: 2-Deoxy-D-streptamine glycosylated at the 4-oxygen with a 6-amino-alpha-D-glucosaminyl group.

InChI:InChI=1/C12H26N4O6/c13-2-5-8(18)9(19)6(16)12(21-5)22-11-4(15)1-3(14)7(17)10(11)20/h3-12,17-20H,1-2,13-16H2

Synthetic route

(1S,2R,3R,4S,6R)-4,6-Diamino-3-((2R,3R,4R,5R,6R)-3-amino-6-aminomethyl-4,5-bis-benzyloxy-tetrahydro-pyran-2-yloxy)-cyclohexane-1,2-diol (549501-35-1) → neomycin A (3947-65-7)

Conditions	Yield
With hydrogen; 20% palladium hydroxide on carbon In water; acetic acid	91%
With hydrogen; acetic acid; palladium dihydroxide

neomycin B (119-04-0) → neomycin A (3947-65-7)

Conditions	Yield
With hydrogenchloride In methanol for 6h; Heating;	82%
With hydrogenchloride In methanol for 4h; Reflux;	80%
Stage #1: neomycin B With hydrogenchloride; methanol for 16h; acidic methanolysis; Stage #2: With Amberlite IRA-400 (OH-) In methanol for 0.5h; Hydrolysis;	67%
With water Acidic conditions; Inert atmosphere;

neomycin B trisulfate → neomycin A (3947-65-7)

Conditions	Yield
Stage #1: neomycin B trisulfate With hydrogenchloride In methanol for 6h; Heating; Stage #2: With ammonium hydroxide; ammonia In methanol Further stages.;	70%

neomycin B trisulfate (4146-30-9, 25389-98-4, 28002-70-2, 34289-38-8, 92283-95-9) → neomycin A (3947-65-7)

Conditions	Yield
With hydrogenchloride In methanol at 80℃; for 3h; pH=< 1;	67%

neomycin B sulphate (25389-98-4) → furfural (98-01-1) + β-D-ribofuranose (36468-53-8) + neomycin A (3947-65-7) + 2,6-dideoxy-2,6-diamino-D-glucose (59433-00-0) + (2R,3S,4R,5R,6R)-5-Amino-2-aminomethyl-6-((2R,3S,4R,5R)-4,5-dihydroxy-2-hydroxymethyl-tetrahydro-furan-3-yloxy)-tetrahydro-pyran-3,4-diol

Conditions	Yield
Product distribution; Rate constant; Irradiation; multistep reaction, radiolytic degradation;

neomycin B sulphate (25389-98-4) → furfural (98-01-1) + β-D-ribofuranose (36468-53-8) + neomycin A (3947-65-7) + (2S,3R,4R,5S,6S)-3-Amino-6-aminomethyl-tetrahydro-pyran-2,4,5-triol + (2S,3S,4R,5R,6R)-5-Amino-2-aminomethyl-6-((2R,3S,4R,5R)-4,5-dihydroxy-2-hydroxymethyl-tetrahydro-furan-3-yloxy)-tetrahydro-pyran-3,4-diol

Conditions	Yield
Product distribution; Rate constant; Irradiation; multistep reaction, radiolytic degradation;

neomycin-B → neomycin A (3947-65-7)

Conditions	Yield
With hydrogenchloride; methanol
With hydrogenchloride

1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-D-glucopyranose (171032-74-9) → neomycin A (3947-65-7)

Conditions

Yield

Multi-step reaction with 9 steps 1: 90 percent / ZnI2 / 1,2-dichloro-ethane / 50 °C 2: 98 percent / NaOMe / methanol 3: 94 percent / pyridine 4: 100 percent / NaN3 / dimethylformamide / 80 °C 5: 86 percent / NaH / dimethylformamide 6: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 7: NaOMe / methanol 8: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 9: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

phenyl 2-azido-2-deoxy-1-thio-α/β-D-glucopyranoside (202462-37-1) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: 94 percent / pyridine 2: 100 percent / NaN3 / dimethylformamide / 80 °C 3: 86 percent / NaH / dimethylformamide 4: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 5: NaOMe / methanol 6: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 7: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

phenyl 2-azido-2-deoxy-3,4,6-tri-O-acetyl-1-thio-α/β-D-glucopyranoside (183875-22-1) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: 98 percent / NaOMe / methanol 2: 94 percent / pyridine 3: 100 percent / NaN3 / dimethylformamide / 80 °C 4: 86 percent / NaH / dimethylformamide 5: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 6: NaOMe / methanol 7: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 8: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

phenyl 2,6-diazido-2,6-dideoxy-1-thio-α/β-D-glucopyranoside (632330-84-8) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 86 percent / NaH / dimethylformamide 2: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 3: NaOMe / methanol 4: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 5: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

Toluene-4-sulfonic acid (2R,3S,4R,5R)-5-azido-3,4-dihydroxy-6-phenylsulfanyl-tetrahydro-pyran-2-ylmethyl ester (632330-83-7) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 100 percent / NaN3 / dimethylformamide / 80 °C 2: 86 percent / NaH / dimethylformamide 3: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 4: NaOMe / methanol 5: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 6: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

(3R,4R,5R,6R)-3-Azido-6-azidomethyl-4,5-bis-benzyloxy-2-phenylsulfanyl-tetrahydro-pyran (549501-23-7) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: N-iodosuccinimide; silver trifluoromethanesulfonate / diethyl ether; CH2Cl2 / -20 °C 2: NaOMe / methanol 3: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 4: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

3′,4′-di-O-benzyl-1,3,2′,6′-tetraazidoneamine (549501-27-1) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 2: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme
Multi-step reaction with 2 steps 1: trimethylphosphane / tetrahydrofuran 2: hydrogen / 20% palladium hydroxide on carbon / water; acetic acid View Scheme

5,6-di-O-acetyl-3',4'-di-O-benzyl-1,3,2',3'-tetraazidoneamine (549501-26-0) → neomycin A (3947-65-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaOMe / methanol 2: P(CH3)3; 0.1 N aq. NaOH / tetrahydrofuran 3: H2; aq. AcOH / 20 percent Pd(OH)2/C View Scheme

neomycin B sulphate (25389-98-4) → neomycin A (3947-65-7)

Conditions	Yield
With hydrogenchloride

butan-1-ol (71-36-3) → neomycin A (3947-65-7)

Conditions	Yield
With acetic acid

neomycin A (3947-65-7) + benzyl chloroformate (501-53-1) → N,N',N'',N'''-tetra(benzyloxycarbonyl)neamine (22854-75-7)

Conditions	Yield
With sodium carbonate In acetone	95%
With sodium hydrogencarbonate In acetone; toluene at 4℃;	86%

di-tert-butyl dicarbonate (24424-99-5) + neomycin A (3947-65-7) → {(1R,2S,3R,4R,5S)-5-tert-Butoxycarbonylamino-4-[(2R,3R,4R,5S,6R)-3-tert-butoxycarbonylamino-6-(tert-butoxycarbonylamino-methyl)-4,5-dihydroxy-tetrahydro-pyran-2-yloxy]-2,3-dihydroxy-cyclohexyl}-carbamic acid tert-butyl ester (54230-72-7)

Conditions	Yield
	95%

C22H31N3O8 + neomycin A (3947-65-7) → C25H48N6O11

Conditions	Yield
In water; acetone for 1h;	92%

C21H30N2O7 + neomycin A (3947-65-7) → C24H47N5O10 (936707-05-0)

Conditions	Yield
In water; acetone for 1h;	92%

C27H24N2O6 + neomycin A (3947-65-7) → C30H41N5O9 (936707-01-6)

Conditions	Yield
In water; acetone for 1h;	91%

di-tert-butyl dicarbonate (24424-99-5) + neomycin A (3947-65-7) → 1,3,2',6'-tetra-N-(tert-butoxycarbonyl)neamine

Conditions	Yield
With triethylamine In methanol; water at 20℃; for 2h;	91%

neomycin A (3947-65-7) + 2-Chloro-benzoic acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl ester (100898-23-5) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-2-chloro-benzamide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	90%
In water; acetonitrile at 20℃; for 0.5h;	90 %Chromat.

neomycin A (3947-65-7) → 1,3,2′,6′-tetraazidoneamine (671809-10-2)

Conditions	Yield
With triflic azide; copper(II) sulfate; triethylamine In methanol; dichloromethane; water Inert atmosphere;	90%
With triflic azide; copper(II) ion	77%
With triflic azide; copper(II) sulfate; triethylamine

γ-L-Glu-((S)-4-amino-2-hydroxybutyryl)-N-acetylcysteamine thioester (1064665-41-3) + neomycin A (3947-65-7) → γ-L-Glu-[(S)-4-amino-2-hydroxybutyryl]-neamine (1141768-83-3)

Conditions	Yield
With recombinant BtrH enzyme at 20℃; for 6h; pH=7.9; aq. buffer; Enzymatic reaction;	90%

C26H22N2O6 + neomycin A (3947-65-7) → C29H39N5O9 (936707-00-5)

Conditions	Yield
In water; acetone for 1h;	89%

neomycin A (3947-65-7) + Boc-β-Ala-ONB (65785-41-3) → C20H39N5O9 (936707-03-8)

Conditions	Yield
In water; acetone for 1h;	87%

Naphthalen-1-yl-acetic acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl ester + neomycin A (3947-65-7) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-2-naphthalen-1-yl-acetamide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	85%
In water; acetonitrile at 20℃; for 0.5h;	85%

neomycin A (3947-65-7) + N-benzoyloxy-5-norbornene-endo-2,3-dicarboximide (24147-30-6) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-benzamide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	80%
In water; acetone for 1h;	80%
In water; acetonitrile at 20℃; for 0.5h;	80%

neomycin A (3947-65-7) + trityl chloride (76-83-5) → (2R,3S,4R,5R,6R)-6-[(1R,2R,3S,4R,6S)-2,3-Dihydroxy-4,6-bis-(trityl-amino)-cyclohexyloxy]-5-(trityl-amino)-2-[(trityl-amino)-methyl]-tetrahydro-pyran-3,4-diol

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide	77%

C12H9NO4 + neomycin A (3947-65-7) → C15H26N4O7

Conditions	Yield
In water; acetone for 1h;	77%

neomycin A (3947-65-7) + trifluoroacetic anhydride (407-25-0) → 1,2',3,6'-tetrakis-N-(trifluoroacetyl)neamine (61066-03-3)

Conditions	Yield
With triethylamine In acetonitrile for 1h; Ambient temperature;	75.3%

neomycin A (3947-65-7) + Phenyl-acetic acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl ester (100898-22-4) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-2-phenyl-acetamide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	75%
In water; acetonitrile at 20℃; for 0.5h;	75%

C11H10N4O4 + neomycin A (3947-65-7) → C14H27N7O7

Conditions	Yield
In water; acetone for 1h;	75%

neomycin A (3947-65-7) + N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide (1092494-97-7) → 6'-N-benzyloxycarbonylneamine (77967-96-5)

Conditions	Yield
In 1,4-dioxane; water at 20℃; for 6h;	72%

endo-N-hydroxy-5-norbornene-2,3-dicarboximide O-bromoacetate (872054-82-5) + neomycin A (3947-65-7) → N-6'-bromoacetylneamine (220874-82-8)

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	70%
In water; acetone for 1h;	70%
In water; acetone for 0.25h; Sonication;
In water; acetonitrile for 0.166667h; Product distribution / selectivity;
In water; acetone for 0.166667h;

Butyric acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl ester + neomycin A (3947-65-7) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-butyramide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	70%
In water; acetonitrile at 20℃; for 0.5h;	70 %Chromat.

Dodecanoic acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl ester + neomycin A (3947-65-7) → Dodecanoic acid [(2R,3S,4R,5R,6R)-5-amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-amide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	70%
In water; acetonitrile at 20℃; for 0.5h;	70 %Chromat.

neomycin A (3947-65-7) + acetone O-<(vinyloxy)carbonyl>oxime (139705-38-7) → {(1R,2S,3R,4R,5S)-4-[(2R,3R,4R,5S,6R)-4,5-Dihydroxy-3-vinyloxycarbonylamino-6-(vinyloxycarbonylamino-methyl)-tetrahydro-pyran-2-yloxy]-2,3-dihydroxy-5-vinyloxycarbonylamino-cyclohexyl}-carbamic acid vinyl ester (791064-36-3)

Conditions	Yield
With sodium hydroxide In phosphate buffer at 0℃; for 5h; pH=8.0;	66%

neomycin A (3947-65-7) + N-(t-butoxycarbonyloxy)-5-norbornene-endo-2,3-dicarboximide → 6'-N-(tert-Butoxycarbonyl)neamine (153953-67-4)

Conditions	Yield
In 1,4-dioxane; water for 5h; Ambient temperature;	65%
With triethylamine In 1,4-dioxane; water at 20℃; for 15.1667h;

2-acetoxy-(3ac,7ac)-3a,4,7,7a-tetrahydro-4r,7c-methano-isoindole-1,3-dione (24147-28-2) + neomycin A (3947-65-7) → N-[(2R,3S,4R,5R,6R)-5-Amino-6-((1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxy-cyclohexyloxy)-3,4-dihydroxy-tetrahydro-pyran-2-ylmethyl]-acetamide

Conditions	Yield
In water; acetonitrile for 0.5h; sonication;	60%
In water; acetone for 1h;	60%
In water; acetonitrile at 20℃; for 0.5h;	60%

Nα-[(thymin-1-yl)acetyl]-Nε-(2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl)-L-arginine + neomycin A (3947-65-7) → 6'-N-[Nα-[(thymin-1-yl)acetyl]-Nε-(2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl)-DL-arginyl]neamine (886208-72-6)

Conditions	Yield
Stage #1: Nα-[(thymin-1-yl)acetyl]-Nε-(2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl)-L-arginine With WSC*HCl In N,N-dimethyl-formamide for 3h; Stage #2: neomycin A In water; N,N-dimethyl-formamide for 20h;	58.3%

Upstream product

• 119-04-0 neomycin B 
• 4146-30-9 neomycin B trisulfate 
• 549501-23-7 (3R,4R,5R,6R)-3-Azido-6-azidomethyl-4,5-bis-benzyloxy-2-phenylsulfanyl-tetrahydro-pyran 
• 632330-83-7 Toluene-4-sulfonic acid (2R,3S,4R,5R)-5-azido-3,4-dihydroxy-6-phenylsulfanyl-tetrahydro-pyran-2-ylmethyl ester 
• 632330-84-8 phenyl 2,6-diazido-2,6-dideoxy-1-thio-α/β-D-glucopyranoside 
• 171032-74-9 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-D-glucopyranose 
• 549501-35-1 (1S,2R,3R,4S,6R)-4,6-Diamino-3-((2R,3R,4R,5R,6R)-3-amino-6-aminomethyl-4,5-bis-benzyloxy-tetrahydro-pyran-2-yloxy)-cyclohexane-1,2-diol 
• 25389-98-4 neomycin B sulphate 
• 549501-26-0 5,6-di-O-acetyl-3',4'-di-O-benzyl-1,3,2',3'-tetraazidoneamine 
• 549501-27-1 3′,4′-di-O-benzyl-1,3,2′,6′-tetraazidoneamine 
• 183875-22-1 phenyl 2-azido-2-deoxy-3,4,6-tri-O-acetyl-1-thio-α/β-D-glucopyranoside 
• 202462-37-1 phenyl 2-azido-2-deoxy-1-thio-α/β-D-glucopyranoside 

Downstream Products

• 14307-02-9 D-mannosamine 
• 936707-05-0 C₂₄H₄₇N₅O₁₀ 
• 936707-00-5 C₂₉H₃₉N₅O₉ 
• 936707-01-6 C₃₀H₄₁N₅O₉ 
• 936707-03-8 C₂₀H₃₉N₅O₉ 
• 153953-66-3 3,6'-di-(N-tert-butoxycarbonyl)-neamine 
• 671809-10-2 1,3,2′,6′-tetraazidoneamine 
• 1141768-83-3 γ-L-Glu-[(S)-4-amino-2-hydroxybutyryl]-neamine 
• 1383687-49-7 3',4'-di-O-acetyl-5-[[(propylamino)carbonyl]oxy]-1,3,2',6'-tetraazidoneamine 
• 1383687-50-0 3',4'-di-O-acetyl-6-[[( propylamino)carbonyl]oxy]-1,3,2',6'-tetraazidoneamine 
• 1383687-51-1 5-[[(propylamino)carbonyl]oxy]-1,3,2',6'-tetraazidoneamine 
• 1383687-52-2 6-[[(propylamino)carbonyl]oxy]-1,3,2',6'-tetraazidoneamine 

Relevant articles and documents

New amphiphilic neamine conjugates bearing a metal binding motif active against MDR E.?aerogenes Gram-negative bacteria

Structure of bacterial envelope is one of the major factors contributing to Gram negative bacterial resistance. To develop new agents that target the bacterial membranes, we synthesized, by analogy with our previous peptide conjugates, new amphiphilic 3′,4′,6-trinaphthylmethylene neamines functionalized at position 5 through a short spacer by a chelating group, tris(2-pyridylmethyl)amine (TPA) and di-(picolyl)amine (DPA) and tetraazacyclotetradecane (Cyclam). ESI+mass spectrometry analyses showed that neither Zn(II)(NeaDPA) nor Cu(II)(NeaCyclam) were stable in the Mueller Hinton (MH) medium used for antibacterial assays. In contrast Zn(NeaTPA) was stable in the MH medium. Interestingly, in MH, the free ligand NeaTPA was found bound to zinc, the zinc salt being the most abundant salt in this medium. Thus, the antibacterial activities of all compounds were evaluated as free ligands against E.?coli strains, wild type AG100 and E.?aerogenes EA289 (a clinical MDR strain that overexpresses AcrAB-TolC efflux pump), as well as AG100A an AcrAB- E.?coli strain and EA298 a TolC- derivative. NeaCyclam and Zn(NeaTPA) were by far the most efficient compounds active against resistant isolate EA289 with MICs in the range 16–4 and 4?μM, respectively, while usual antibiotics such as β-lactams and phenicols were inactive (MICs?>?128) and ciprofloxacin was at 64?μM. Zn(NeaTPA) and NeaCyclam were shown to target and permeabilize the outer membrane of EA289 by promoting the cleavage of nitrocefin by periplasmic β-lactamase. Moreover, all the neamine conjugates were able to block the efflux of 1,2’-dinaphthylamine in EA289, by acting on the efflux transporter located in the inner membrane. These membranotropic properties contribute to explain the activities of these neamine conjugates toward the MDR EA289 strain.

Neamine Compositions and Methods of Use Thereof

Provided herein are compositions containing neamine, or a composition containing an agent that possesses one or more activities of neamine, and the research, diagnostic and therapeutic uses of such compounds, such as for the treatment of cancer.

Neamine Compositions and Methods of Use Thereof

Provided herein are compositions containing neamine, or a composition containing an agent that possesses one or more activities of neamine, and the research, diagnostic and therapeutic uses of such compounds, such as for the treatment of cancer.