SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NOVEL α-AMINOPHOSPHONATES BEARING A QUINOLINE MOIETY

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NOVEL α-AMINOPHOSPHONATES BEARING A QUINOLINE MOIETY

Ahmed A. El Gokha ¹, Ibrahim M. S. Ghanim ¹, Ahmed El S. Abdel Megeed ¹, Elkhabiry Shaban ² and Ibrahim El-Tantawy El Sayed ^1*

Department of Chemistry ¹, Faculty of Science, El Menoufia University, Shebin El Koom, Egypt

Textile Research Division ², National Research Centre, Dokki, Cairo, Egypt

ABSTRACT: A novel aminophenylaminoquinoline analogues have been synthesized starting from 4,7 dichloroquinloine and (p-phenylenediamine 2a, o-phenylenediamine 2b or m-phenylenediamine 2c). The one pot reaction with aldehydes and triphenylphosphite in presence of LiClO₄ as a Lewis acid catalyst led to the formation of novel α-aminophosphonate derivatives bearing quinoline moiety in good yields. The synthesized compounds have been characterized on the basis of the spectral analysis.  All the synthesized compounds were screened for in vitro antibacterial activity and most of them showed a potency against both gram positive and gram negative bacteria

Aminoquinoline, aldehydes, triphenylphosphite, Lewis Acid, α-aminophosphonates, Antibacterial Activity

INTRODUCTION: Organ phosphorus compounds have found a wide range of applications in the areas of industrial, agricultural, and medicinal chemistry owing to their biological and physical properties as well as their utility as synthetic intermediates. ¹ α-Functionalized phosphonic acids are valuable intermediates for the preparation of medicinal compounds and synthetic intermediates. ^{2, 3} Among α-functional phosphonic acids, α-aminophosphonic acids are an important class of compounds that exhibit a variety of interesting and useful properties. These compounds have already been found to act as α-Aminophosphonic acids I, as structural mimics of α-amino acids II (cf. Fig. 1), exhibit a broad spectrum of biological activities.^5-11

FIG.1: STRUCTURES OF α-AMINOPHOSPHONATES I, α AMINO ACID II AND QUINOLINE III

Antibacterial agents, neuroactive compounds, anticancer drugs, and pesticides, with some of them already commercialized. ^11-27 In this context, The therapeutic potential for modified α-aminophosphonates with improved pharmacokinetic properties, potency or spectrum, and lower side effects, prompted us to start a synthetic program to explore new quinoline aminophosphonate conjugates. We focused on quinoline and its derivatives because it is an important class of compounds and attracted widespread attention due to their pharmacological properties, being reported to have a large spectrum of biological effects, especially antimalarial, antibacterial and anticancer properties. In this paper we would like to present the synthesis of novel quinoline modified α - aminophosphonates conjugates.

Materials:

All 1HNMR experiments (solvent DMSO) were carried out with a 300 MHz at Cairo University, Egypt. Chemical shifts are reported in part per million (ppm) relative to the respective solvent. The mass spectroscopy experiments were performed at Cairo University, Egypt. Melting points were recorded on Stuart scientific melting point apparatus and are uncorrected. The microanalysis were performed in microanalysis laboratory at National Research Centre (NRC), Egypt. All reactions were followed by thin layer chromatography (TLC) on kiesel gel F254 precoated plates (Merck). Starting materials, MeOH, DMF, acetonitrile, CH₂Cl₂, hexane and diethylether were either commercially available as reported in literature.

Procedure for the synthesis N1-(7-chloroquinolin-4-yl)benzene-1,4-diamine (3a) ²⁷:

(1 mmol) 4,7 dichloroquinoline dissolved in MeOH and excess of the appropriate amine (2 mmol) p-phenylenediamine were heated at reflux  at 135-155 ºC for 10-15 minutes. TLC monitoring was used to ensure the completion of reaction. The solid formed was collected by filtration.

General procedure for the synthesis N1-(7-chloroquinolin-4-yl) benzene-1, 2  -diamine (3b) and N1-(7-chloroquinolin - 4 - yl)benzene - 1, 3-diamine (3c) ²⁷: 4,7 dichloroquinoline dissolved in dry DMF and an excess of the appropriate amine o-phenylenediamine or m-phenylenediamine were heated at reflux  at 135-155 ºC in presence of 10 eqs.  of triethyl amine for 4h. TLC monitoring was used to ensure the completion of reaction. The resulting crude poured into ice water and the solid formed was collected by filtration and dried.

General procedure for the synthesis:

α-aminophosphonate derivatives (6a-g), (7a-c) & (8a-g): Aldehyde (1.2 mmol), aminophenyl aminoquinoline derivatives (1 mmol) and triphenylphosphite were dissolved in acetonitrile (5 ml) and stirred at r.t about 15 minutes. Then the lewis acid, LiClO₄ (10 mmol%) was added in one portion. The mixture was stirred at r.t, until TLC analysis showed the complete consumption of aminophenylaminoquinoline derivatives with using hexane and CH₂Cl₂ as eluent. Then for aminophosphonate derivatives of compund 3a and 3c the collection of the precipitate by filteration afford the protected α-aminophosphonates in good to excellent yields, but for α-aminophosphonate derivatives of compound 3b, acetonitrile evaporated and the residue dissolved in diethylether, the product was percipitated from this solution immediately followed by the collection of the precipitate by filteration afford the protected aminophosphonates in good to excellent yields.

N1-(7-chloroquinolin-4-yl) benzene-1,4- diamine (3a): Show the following data m.p = 208-210 ^◦C, Yield = 91 % , Dark yellow solids, The Infra- red spectra of compound show characteristic bands for ν_NHat 3430 cm^-1  and at 3317 cm^-1 corresponding to ν_NH, ¹HNMR ( DMSO): δ ppm = 6.6(m, 1H, HAr), 6.8(d,  J=8.4Hz, 1H, HAr), 7.1(d, J=9Hz, 2H, HAr), 7.8(d,  J=8.4Hz, 2H, CHquinoline), 8.1(d, J=4.8Hz, 1H, CHquinoline), 8.4(d, J=6.9Hz, 1H, CHquinoline), 8.7(d, J=9.3Hz, 1H, CHquinoline), 10.7(s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 272 (M+3,7%).

N1-(7-chloroquinolin-4-yl) benzene- 1,2-diamine (3b): Show the following data m.p = 215-217^◦C, Yield = 85%, Pale brown solids, ¹HNMR ( DMSO): δ ppm = 6.2 (d, J=3.6Hz, 2H, HAr),  6.6 (m, 1H,  HAr), 6.9 ( m , 1H, CHAr), 7.8 -7.9 (m, 2H, CHquinoline) , 8.1 – 8.2 (m, 3H , CHquinoline),  8.8 (d, J=4.5Hz, 1H, NH), The mass spectra show the molecular ion peak at m/e = 270(M+1,23%).

N1-(7-chloroquinolin-4-yl) benzene- 1,3-diamine (3c): Show the following data m.p = 205-207 ^◦C, Yield =76 %, Dark gray solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3276 cm^-1  and at 3387 cm^-1 corresponding to ν_NH  ¹HNMR ( DMSO): δ ppm = 6.4(m, 1H, HAr), 6.6(m,1H, HAr), 6.9(m, 1H , CHAr), 7.4(m, 1H, CHAr), 7.9 – 8.1(m, 2H, CHquinoline), 8.4(d, J=6.3Hz, 1H, CHquinoline), 8.5(d, J=7.5Hz, 1H, CHquinoline), 8.9(s, 1H, CHquinoline), 9.1(s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 262 (M+3,6%).

Diphenyl (((4-((7-chloroquinolin-4-yl) amino) phenyl)amino) (phenyl)methyl) phosphonate (6a): Show the following data m.p =  265-267^◦C Yield =  90%, pale yellow solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3320 cm^-1  and at 3431 cm^-1 corresponding to ν_NH and at 1227cm^-1 corresponding to ν_P=O and at 1004 cm^-1 corresponding to ν_POC, ¹HNMR ( DMSO): δ ppm = 5.8 ( s , 1H, CHP), 6.6 (d, J=6.9Hz, 2H, HAr) , 6.7 (t, J=3Hz, 4H, HAr), 7 – 7.2 (m, 7H, HAr), 7 .3 (m, 6H, HAr) , 7.8 – 8.1 (m, 3H, CHquinoline) , 8.4 ( d, J=6.9Hz, 1H, CHquinoline) , 8.8 (d, J=9.3Hz, 1H, CHquinoline) , 10.9 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 595 (M+3,54% ).

Diphenyl ([1,1'-biphenyl] – 4 – yl ((4-((7-chloroquinolin-4-yl) amino) phenyl) amino) methyl)phosphonate (6b):

Show the following data m.p =245-248^◦C Yield =92% , dark yellow solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3318 cm^-1  and at 3430 cm^-1 corresponding to ν_NH and at 1230cm^-1 corresponding to ν_P=O and at 1011 cm^-1 corresponding to ν_POC, ¹HNMR ( DMSO): δ ppm = 6.6 – 6.7(m, 4H, HAr), 6.8 – 6.9(m, 5H, HAr), 7 – 7.7(m, 15H, HAr), 8.1(s, 1H, CHquinoline), 8.4(d, , J=6.6Hz, 2H, CHquinoline),

8.7(d, J=5.1Hz, 1H, CHquinoline), 8.8(s, 1H, CHquinoline), 10.8 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 700 (M+2, 21%).

Diphenyl (((4-((7-chloroquinolin-4-yl) amino) phenyl) amino) (1H – indol – 3 - yl) methyl) phosphonate (6c):

Show the following data m.p = 252-254 ^◦C Yield = 85 %, yellow solids, ¹HNMR ( DMSO): δ ppm = 6.6(d, J=6.9Hz, 3H, HAr) , 6.7(m, 2H, HAr), 6.9 -7.1(m, 13H, HAr ), 7.7 (m, 1H , CHquinoline), 8.1

(d, J=1.5Hz, 1H, CHquinoline), 8.4(d, J=7.2Hz, 2H, CHquinoline), 8.7(d, J=9.3Hz, 1H, CHquinoline),  10.7 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 633  (M+2,17% ).

Diphenyl (((4-((7-chloroquinolin-4-yl) amino) phenyl) amino) (4-methoxyphenyl) methyl) phosphonate (6d):

Show the following data m.p = 240-243 ^◦C Yield = 88 % , dark yellow solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3318 cm^-1  and at 3430 cm^-1 corresponding to ν_NH and at 1229cm^-1 corresponding to ν_P=O and at 1018 cm^-1 corresponding to ν_POC , ¹HNMR ( DMSO): δ ppm = 3.8(d, J=3.9Hz, 3H, CH3), 6.6(d, J=6.9Hz, 4H, HAr), 6.7(d, J=6.5Hz, 3H, HAr), 7(d, J=8.1Hz, 11H, HAr), 7.7(d, J=8.7Hz, 2H , CHquinoline), 8.1(s, 1H, CHquinoline), 8.4(d, J=6.6Hz, 1H , CHquinoline), 8.8(d, J=9Hz, 1H, CHquinoline),  10.8 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 625 (M+3,38%).

Diphenyl (((4-((7-chloroquinolin-4-yl) amino) phenyl) amino) (2-hydroxynaphthalen-1-yl) methyl) phosphonate (6e):

Show the following data m.p = 274-276^◦C Yield =93%, yellow solids, ¹HNMR ( DMSO): δ ppm =

4.8 (s , 1H , CHP), 6.5 – 6.7(m, 4H,  HAr), 7.0– 7.3(m,16H, HAr), 7.8 - 7.9(m, 2H, CHquinoline), 8-8.1 ( m, 2H, CHquinoline) , 8.9(d, J=8.7Hz,  1H, CHquinoline), 10.9(s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 661 (M+3,64%).

Diphenyl(((4-((7-chloroquinolin-4 - yl) amino) phenyl) amino) (4-(dimethylamino) phenyl)methyl) phosphonate (6f):

Show the following data m.p = 231-234 ^◦C Yield = 92 %, yellow solids, ¹HNMR (DMSO): δ ppm = 5.1(S, 1H, CHP), 6.6(d, J=5.4Hz, 4H, HAr), 6.7(d, J=7.2Hz, 3H, HAr), 7.1(d,  J=8.4Hz, 11H, HAr), 7.7 (t, J=8.7Hz, 2H , CHquinoline), 8.1(s, 1H, CHquinoline),  8.3(d, J=6Hz, 1H , CHquinoline), 8.8(d, J=9.3Hz, 1H, CHquinoline), 10.8 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 636 (M+1,52%).

Diphenyl ((4-chlorophenyl) ((4-((7-chloroquinolin-4-yl) amino) phenyl) amino) methyl) phosphonate (6g):

Show the following data m.p = 269-271^◦C Yield =91%, dark yellow solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3329 cm^-1  and at 3438 cm^-1 corresponding to ν_NH and at 1235cm^-1 corresponding to ν_P=O ,¹HNMR ( DMSO): δ ppm = 6.6(t, J=7.2Hz , 2H, HAr), 6.7(m, J=7.2Hz, 2H, HAr), 7 – 7.1(m, 3H, HAr), 7.4 – 7.6 (m, 11H, CHAr), 7.8 (d, J=9.3Hz, 2H, CHquinoline), 8.1(s, 1H , CHquinoline),

8.4(d, J=6.9Hz, 1H, CHquinoline), 8.7(d, J=9Hz, 1H, CHquinoline), 10.8 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 628 (M+2,60%).

Diphenyl (((2-((7-chloroquinolin-4-yl) amino) phenyl)amino)(phenyl)methyl)phosphonate (7a):

Show the following data m.p = 278-279 ^◦C Yield = 86 % , pale brown solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3427 cm^-1  and at 1207cm^-1 corresponding to ν_P=O and at 1003 cm^-1 corresponding to ν_POC, ¹HNMR ( DMSO): δ ppm = 5.8 (s, 1H, CHP),7.1(m, 7H, HAr), 7.3 – 7.4(m, 12H, HAr), 7.8(m, 2H, CHquinoline), 8.1 – 8.3(m, 3H, CHquinoline),  8.8(d, J=4.5Hz, 1H, NH), The mass spectra show the molecular ion peak at m/e = 595  (M+3,74%).

Diphenyl([1,1'-biphenyl] – 4 – yl ((2-((7-chloro quinolin-4-yl)amino)phenyl) amino) methyl) phosphonate (7b): Show the following data m.p = 289-292 ^◦C Yield =80 % , dark brown solids, The Infra- red spectra of compound show characteristic bands for ν_NH at 3435 cm^-1  and at 1207cm^-1 corresponding to ν_P=O and at 1005 cm^-1 corresponding to ν_POC, ¹HNMR ( DMSO): δ ppm = 5.8(s , 1H, CHP), 6.7(t, J=6.9Hz, 7H, HAr), 7.1(d, J=7.5Hz, 6H, HAr), 7.3(m, 10H, HAr), 7.8(t, J=9.3Hz, 2H, CHquinoline), 8.1 – 8.2(m, 3H, CHquinoline),  8.9(d, J=5.1Hz, 1H, NH), The mass spectra show the molecular ion peak at m/e = 670  (M+2,26%).

Diphenyl (((2-((7-chloroquinolin – 4 - yl) amino) phenyl) amino) (1H-indo l- 3 - yl) methyl) phosphonate (7c): Show the following data m.p = 243-245 ^◦C Yield = 92%, dark brown solids, ¹HNMR ( DMSO): δ ppm = 6.7(d, J=8.4Hz , 2H, HAr), 7.1 – 7.3(m, 8H, HAr), 7.5(d, J=7.5Hz, 4H, HAr), 7.8(s, 2H, CHquinoline), 8.0 – 8.2(m, 3H , CHquinoline), 9.9(s, 1H, NH), 12.1(s, 1H, NHindol), The mass spectra show the molecular ion peak at m/e = 631  (M,73%).

Diphenyl (((3-((7-chloroquinolin-4-yl) amino) phenyl) amino) (phenyl) methyl) phosphonate (8a): Show the following data m.p = 282-286 ^◦C Yield = 86 % , pale gray solids, show characteristic bands for ν_NH at 3276 cm^-1  and at 3426 cm^-1 corresponding to ν_NH and at 1208cm^-1 corresponding to ν_P=O and at 1000 cm^-1 corresponding to ν_POC, ¹HNMR ( DMSO): δ ppm = 5.8(s, 1H , CHP), 6.8 – 6.9(m, 4H, HAr), 7 – 7.2(m, 5H, HAr), 7.3 – 7.6(m, 10H, HAr), 7.8 – 7.9(m, 2H, CHquinoline), 8.4 – 8.5(m, 3H, CHquinoline),  9.4 (s, 1H, NH), The mass spectra show the molecular ion peak at m/e = 593  (M+1,56%).

Diphenyl ([1,1'-biphenyl] – 4 – yl ((3-((7-chloroquinolin-4-yl)amino) phenyl) amino) methyl)phosphonate (8b):

Show the following data m.p =  277-279^◦C Yield =79 %, pale gray solids, ¹HNMR ( DMSO): δ ppm = 6.8(d, J=6Hz, 4H, HAr),  7 – 7.2 (m, 6H, HAr), 7.3 – 7.6(m, 13H, HAr) ,7.8 – 8(m, 2H , CHquinoline), 8.4 (d, J=8.7Hz, 1H , CHquinoline), 8.5(d,  J=4.8Hz, 2H, CHquinoline), 9.1(s, 1H, NH),

The mass spectra show the molecular ion peak at m/e = 670 (M+2,8%).

Diphenyl (((3-((7- chloroquinolin–4 -yl) amino) phenyl) amino) (1H-indol-3-yl) methyl) phosphonate (8c):

Show the following data m.p = 252-255 ^◦C Yield = 84 %, pale gray solids, ¹HNMR (DMSO): δ ppm =

5.8(s, 1H, CHP), 6.8 -6.9(m, 4H, HAr), 7 – 7.5(m, 15H, HAr), 7.8 – 7.9(m, 2H, CHquinoline), 8.4(d, J=8.7Hz, 2H, CHquinoline), 8.5(d, J=5.4Hz, 1H, CHquinoline), 9.1(s, 1H, NH), The mass spectra show the molecular ion peak at m/e =634 (M+3,83%).

Diphenyl (((3-((7-chloroquinolin-4-yl) amino) phenyl) amino) (4 - methoxyphenyl) methyl) phosphonate (8d):

Show the following data m.p = 263-267 ^◦C Yield = 88 %, pale gray solids, ¹HNMR (DMSO): δ ppm = 3.8(m, 3H, CH3), 5.8(s, 1H, CHP), 6.8-6.9(m, 5H, HAr), 7 -7.1(m, 5H, HAr), 7.3(s, 1H,  HAr),7.4(d, J=8.1Hz, 2H,  HAr),  7.5 – 7.6(m, 5H, HAr), 7.9(d, J=1.8Hz, 2H, CHquinoline),  8.4(d, J=9Hz, 2H, CHquinoline), 8.5(d, J=5.1Hz, 1H, CHquinoline), 9.1(s, 1H, NH), The mass spectra show the molecular ion peak at m/e =625 (M+3,31%).

Diphenyl (((3-((7-chloroquinolin-4-yl) amino) phenyl) amino)(2-hydroxynaphthalen – 1 - yl) methyl) phosphonate (8e):

Show the following data m.p = 224-226^◦C Yield =  93 % , dark gray solids,¹HNMR ( DMSO): δ ppm =

6.7(t, J=8.1Hz, 4H, HAr), 7-7.1(m, 5H,  HAr), 7.3 – 7.7(m, 11H,  HAr), 7.9(d, J=5.4Hz, 2H,  CHquinoline), 8.4 – 8.5(m , 3H, CHquinoline),  9.6(s, 1H, NH), The mass spectra show the molecular ion peak at m/e =657  (M-1, 87%).

Diphenyl (((3-((7-chloroquinolin-4-yl) amino) phenyl) amino) (4-(dimethylamino) phenyl) methyl) phosphonate (8f):

Show the following data m.p = 210-215 ^◦C Yield = 82% , dark gray solids, ¹HNMR ( DMSO): δ ppm = 5.8(s, 1H, CHP), 6.7 – 6.9(m, 5H, HAr), 7-7.2(m, 4H, HAr), 7.3 – 7.6(m, 9H,  HAr), 7.8-7.9(m, 2H , CHquinoline), 8.4(d, J=8.7Hz, 2H , CHquinoline), 8.5(d, J=5.4Hz, 1H, CHquinoline), 9.1(s, 1H, NH), The mass spectra show the molecular ion peak at m/e =636  (M+1,35%).

 Diphenyl ((4-chlorophenyl) ((3-((7-chloro quinolin-4-yl) amino) phenyl) amino) methyl) phosphonate (8g):

Show the following data m.p = 274-278 ^◦C Yield = 86 %, pale gray solids, ¹HNMR ( DMSO): δ ppm = 6.7 – 6.8(m, 4H, HAr), 7-7.1 (m, 3H, HAr), 7.3 – 7.6(m, 11H,  HAr), 7,9(m, 2H, CHquinoline), 8.4 (d,  J=8.7Hz, 2H , CHquinoline), 8.5(d, J=5.4Hz, 1H, CHquinoline), 9.2(s, 1H, NH), The mass spectra show the molecular ion peak at m/e =626 (M, 17%).

RESULTS AND DISCUSSION:                                     

Chemistry: Our strategy for synthesis of 4,7 dichloroquinoline analogues was based on the amination of 4-chlorosubstituted quinoline compound 1 obtained through scheme 1. This method is used for synthesis of quinoline with N-substitutions at 4-substitution. Thus, aminophenylaminoquinoline 3a-c were prepared with various amino- containing groups 2a-c in position 4, which was aminated via SN_Ar in MeOH  with the appropriate amines 2a at high temperature, yielding target compounds 3a, 4,7dichloroquinoline was aminated via SN_Ar in DMF  with the appropriate amines 2b,2c  at high temperature, yielding target compounds 3b,3c as shown in Schemes 1 and 2.

SCHEME: 1

SCHEME: 2

The synthesis of α-aminophosphonates 6,7,8 bearing quinoline skeleton were accomplished in good yield using aminophenylaminoquinoline 3, (benzaldehyde, 4-biphenylcarboxaldehyde, indole-3-aldehyde, anisaldehyde, 4-chlorobenzaldehyde,

2-hydroxynaphthaldehyde or 4-Dimethylamino) benzaldehyde) and triphenylphosphite in the presence of a Lewis acid such as LiClO₄ and acetonitrile as solvent according to schemes 3,4 and 5.

SCHEME: 3

SCHEME: 4

SCHEME: 5

Moreover, the SCHEME: 5

mechanism of this reaction has not been investigated in detail. However, we firstly proposed that the reaction of the aldehydes 4a-g with the amino-compounds 3a-c in the presence of lithum percholorate as a lewis acid (LA) catalyst afforded the corresponding imine- intermediates 10 according to scheme 6. Then, the imine intermediate 10 is attacked by nucleophilic phosphite 5 leading to the formation of a phosphonium intermediate 11 and most likely this step is catalyzed by the Lewis acid (LA). Reaction of phosphonium intermediates 11 with water afforded the target α-aminophosphonates 12 after elimination of phenol as shown in Scheme 6.

    SCHEME: 6

Antibacterial Screening:                                    

The diverse biological activities of aminophenylaminoquinoline derivatives and their α-aminophosphonates prompted us to test and study the antibacterial activities of some of the newly synthesized products. Many antimicrobial agents have been introduced into therapy; however the field still needs extensive efforts for the development of new antibacterial agents to overcome the highly resistant strains of microorganisms. The newly synthesized compounds were tested in vitro for their antibacterial activity against Escherichia coli (Gram -ve bacteria), Bacillus subtilis (gram +ve bacteria) and Staphylococcus aureus (Gram +ve bacteria), Klebsiela Spp (gram –ve bacteria) and pseudomonas aeruginosa (gram –ve bacteria). DMSO was used as a control solvent and Cefotaxim, as a reference drug. After 18-24h incubation at 37ºC, the zone of inhibition was measured in mm. The results are depicted in table 1. It should be noted that compounds 3b and 7a-c showed the best antibacterial activity against all tested bacterial strains as shown in Table 1. It is worth noting that the presence of α-aminophosphonate moiety at fourth position of the quinoline system significantly increases the antibacterial activity against bacterial strains.

TABLE 1: IN VITRO SCREENING OF SAMPLES FOR ANTIMICROBIAL ACTIVITY AFTER SOLUBILITY IN DMSO SOLVENT ON COLD AFTER 24 h:

**= MIC For each microorganism(used as stander)      Nil= No antimicrobial activity

CONCLUSION: New aminophenyl aminoq uinoline derivatives and their α-aminophosphonates analogues were synthesized and evaluated for their antibacterial activities. Some tested compounds showed strong antimicrobial activity against all tested pathogenic bacteria.

ACKNOWLEDGEMENT: The authors are thankful to the Department of organic chemistry of Menoufia University, Egypt for providing literature survey facility to carry out the work.

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    How to cite this article:

    El Gokha AA, Ghanim IMS, El S. Abdel Megeed E, Shaban E and El-Tantawy El Sayed I: Synthesis and Antibacterial Activity of Novel α-Aminophosphonates Bearing a Quinoline Moiety. Int J Pharm Sci Res 2016; 7(1): 181-89.doi: 10.13040/IJPSR.0975-8232.7(1).181-89.

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