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Synthesis and Antibacterial Activity of Novel Cyclic α-Aminophsophonates

Authors:
Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936. 17609
Research Article
ISSN: 2574 -1241
Synthesis and Antibacterial Activity of Novel Cyclic
α-Aminophsophonates
Ibrahim El Tantawy El Sayed*, Ghady Fathy and Abdullah A S Ahmed
Department of Chemistry, Egypt
*Corresponding author:
El-Kom, Egypt
DOI: 10.26717/BJSTR.2019.23.003936
Introduction
-Aminophosphonates I gained great interest of medicinal
       
stability and their weak toxicity towards mammalians. These
organometallic compounds are phosphorus analogues of naturally
occurring -amino acids II (cf   
–aminophosphonates was reported in literatures as anticancer
      
        
    –aminophosphonates considered
  
     
  
      
         

       
with     
        
 
–aminophosphonates bearing quinoline nucleus. Further aim
is to screen the resulting hybrids as antibacterial agents against


Figure 1: Structures of α -Aminophosphonates I, α -Amino
acids II andquinoline III.
Materials and Methods
All 1H-NMR experiments (DMSO-d6 and CDCl3) were carried out
     

Warfare Laboratories, Egypt. Chemical shifts are reported in part

Received: 
Published: December 06, 2019
Citation: Ibrahim El Tantawy El Sayed,
Ghady Fathy, Abdullah A S Ahmed. Syn-
     -
   Biomed
      
MS.ID.003936.
ARTICLE INFO Abstract
          
temperature with good yields by three one-pot reaction of glutaraldehyde 1 with
    


  

            
screened for their in vitro  Klebsiella pneumonia
and E. coli

Keywords:     

Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936.
Volume 23- Issue 4 DOI: 10.26717/BJSTR.2019.23.003936
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
      
  
       
        
Control Research, Egypt. All reactions were followed by thin layer

   
diphenyl phosphite and triphenyl phosphite were commercially

dichloromethane, hexane, dimethylformamide and diethyl ether
       
       

Synthesis of α -Aminophosphonate Derivatives Using
Triphenyl Phosphites
General Procedure for The Synthesis of
α-Aminophosphonate Derivatives (4a-e): To solution of glutaral-

-
lyst LiClO (2.1 mg, 10% mol) was added. The reaction mixture was
stirred at r.t and the completion of the reaction was monitored by

afford 
Diphenyl (α-Aminopiperidin-2-yl) Phosphonate 4a: Yield
    -1 
(NH2    
     17H21N2O3   +
found: 332.26. 1H-NMR (DMSO-d6   1.13 (m, 2H,
CH2 2   2), 6.02 (s, 1H, CH-
 31P-NMR (DMSO d6: -17.17
ppm
Diphenyl (α-(2-Aminoethyl) Piperidin-2-yl) Phosphonate
4b-1
2
      19HN2O3P), calcd.: 360.39
+1H-NMR (DMSO-d6: 1.13 (m,
2H, CH222
CH2), 6.00 (s, 1H, CH
Diphenyl (α-(3-Aminopropyl) Piperidin-2-yl) Phosphonate
4c:     -1
2
     20H27N2O3   +
  1H-NMR (DMSO d6   : 1.16(m, 2H,
CH2222), 3.79
(m, 2H, N-CH2), 6.07 (s, 1H, CH-P), 6.73-7.33 (m, 10H, Ar-H).
Diphenyl (α-(3-Aminophenyl) Piperidin-2-yl) Phosphonate
4d:  -1  
(NH2
    23HN2O3   + 
1H-NMR (DMSO d62), 2.23
(br.m, 2H, CH2), 3.96 (br.m, 2H, CH22), 6.07 (s,
1H, CH2).
Diphenyl (α-(4-Aminophenyl) Piperidin-2-yl) Phosphonate
4e:         -1 : 3370
(NH2
    23HN2O3   + 
 1H-NMR (DMSO d6       2),
2H
General Procedures for Synthesis of α-Aminophosphonate
Derivatives Bearing Quinoline Moiety: (7a-e): Glutaraldehyde
         

of LiClOas Lewis acid catalyst (2.1 mg, 10% mol.) was added. The
reaction mixture was stirred at r.t and the completion of the reaction

off and dried to afford -aminophosphonates 9 with goodyields.
Diphenyl(α-((7-Chloroquinolin-4-yl) Amino) Piperidin-2-
yl) Phosphonate 7a:   
󰒇C, IR (KBr) cm-1   
    ,     
 26HClN3O3  +   1H-NMR
(DMSO d62), 6.10 (s, 1H, CH-
Ar).
Diphenyl(α-(2-((7-Chloroquinolin-4-yl) Amino) Ethyl)
Piperidin-2- yl) Phosphonate 7b:     
     󰒇C, IR (KBr) cm-1  
     , 
    H29ClN3O3  .97 +
 .79. 1H-NMR (DMSO d6   ppm: 1.20 (br.s,
2H, CH2 2 2 
2H, CH2 H  
CH=NAr).
Diphenyl(α-(3-((7-Chloroquinolin-4-yl) Amino) Propyl)
Piperidin-2-yl) Phosphonate 7c:     
yellow solids, m.p = 106-110 󰒇C, IR (KBr) cm-1
    , 
   29H31ClN3O3 +
1H-NMR (CDCl32),
22), 3.79 (br.m, 6H, 3CH2), 6.17
(s, 1H, CHAr, J
9.22 (br.s, 1H, NH). 31P-NMR (DMSO d6   ppm: 0.310,
-1.709.
Diphenyl (α-(3-((7-Chloroquinolin-4-yl) Amino) Phenyl)
Piperidin-2-yl) Phosphonate 7d:     
solids, m.p = < 300 󰒇C, IR (KBr) cm-1
 ,   
  32H29ClN3O3   +  
Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936.
Volume 23- Issue 4 DOI: 10.26717/BJSTR.2019.23.003936
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1H-NMR (DMSO d62
1H, CHAr
1H, NH).
Diphenyl(α-(4-((7-Chloroquinolin-4-yl) Amino) Phenyl)
Piperidin-2-yl) Phosphonate 7e: 
 󰒇C, IR (KBr) cm-1   
, 1230 (P=O),
  32H29ClN3O3 + 
1H-NMR (DMSO d6: 1.16 (m, 2H, CH2
(br.m, 6H, 3CH2H
(d, 1H, CH=NAr, J
Biological Screening
Bacterial Strains
      
was tested against a set of E.coli ATCC 11229, Staphylococcus
aureus  and human MDR pathogenic clinical strains of
Klebsiella pneumonia E. coli (E13,
  Staphylococcus aureus
       

at 37°C
Compounds Preparation for Antimicrobial Activity



on the growth of microorganisms.
Agar Well Diffusion Method
   l bacterial suspension (106  

plates using sterile cork borer, and then 100 l of each prepared
compound was introduced into appropriately marked wells, then
       °C. DMSO was taken as a

   
.
Result and Discussion
Chemistry
-aminophsophonates

          
phosphite 3 (0.39 mL, 2 mmol) in presence of (LiClO) in acetonitrile

scheme 1. 
the absorption bands of (NH2-1 and
(P=O) from 1367 to 1226 cm-1. The 1H-NMR spectra showed the
chemical shift of (CH
    -aminophosphonate. It is
noticeable that the absence of the aldehydic group (CHO) in 1H-NMR
     -aminophosphonates through
  
    throughout the
coincidence of the molecular ion peak with expected mass.
Scheme 1: Synthesis of α-aminophosphonate.
The recommended mechanism for preparation of cyclic
-aminophosphonates using LiClO as a catalyst illustrated in
         
of glutaraldehyde by Lewis acid catalyst (LiClO) followed by
condensation of the carbonyl group of the starting dialdehyde with
primary amines to afford the Schiff base B. Then the nitrogen of
-aminophosphonates
formation donates a pair of electron to make a coordinante bond
with LiClO
2 carbon followed by nucleophilic attack
of nitrogen of Schiff base on carbon atom of the other carbonyl group
of glutaraldehyde. Then the free pair of electrons of phosphorus
         
elimination of phenol C and afford cyclic - aminophosphonates
as depicted in Scheme 3.     
-aminophsophonate bearing quinoline moiety was accomplished
  
 (2 mmol)and diphenyl phosphite 7
Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936.
Volume 23- Issue 4 DOI: 10.26717/BJSTR.2019.23.003936
17612
(0.37 mL, 2 mmol) in presence of Lewis acid catalyst (LiClO) and acetonitrile with equal molar ratios (1:1:1) to get the desired product
with good yields.
Scheme 2: Suggested mechanism of α-aminophsophonate.
Scheme 3: Synthesis of α-aminophsophonate bearing 4.7 dichloroquinoline.
Scheme 4: A plausible mechanism of α-aminophsophonate bearing 4.7 dichloroquinoline.
Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936.
Volume 23- Issue 4 DOI: 10.26717/BJSTR.2019.23.003936
17613
In the structure elucidation of installation of 7, the IR spectra
 2)
  -1  -
1. The 1H-NMR spectra showed the chemical shift of (CH-P) as

formation of -aminophosphonate. While the aromatic (CH=N) of

absence of the aldehydic group (CHO) in 1  
formation of cyclic -aminophosphonates through intra molecular
       
     throughout the coincidence of the
molecular ion peak with expected mass.A proposed mechanism
of formation of 7 was established. A plausible mechanism for
preparation of -aminophosphonates using LiClO as a catalyst
         
        

. Then the free pair of
        
carbon of the other carbonyl group of glutaraldehyde, which was
, followed nucleophilic attack of phosphorus to
the carbon of imine double bond to afford the target compound 7.
Biological Evaluation
In vitro, two groups of synthetic chemical compounds, cyclic
-amino phosphonate using tri phenylphosphiteand cyclic -amino
phosphonate bearing quinolone moiety, were tested against
MDR strains of E.coli and K. pneumonia that already resistant to
  Staphylococcus aureus   S.
aureus    Candida albicans using well diffusion
         
The cyclic -amino phosphonate using tri phenylphosphite
     
tested microorganisms, where diphenyl (1-aminopiperidin-2-yl)

(Table 1). MDR E. coli 17 and K. pneumonia (with gyrase mutation at

     
substitution with other diamines as ethylene diamine, 1.3 di amino
       
      

Table 1: Antimicrobial activity of cyclic α-amino phosphonate using tri phenylphosphite against tested microorganisms.
Chemical
Formula
Bacterial Species (Inhibition zones mm ± SD*)
Gram-Negative Bacteria Gram-Positive bacteria
CIP-Resistant E. Coli CIP-Resistant Klebsiella Pneumonia E. coli ATCC
11229
Staph. Aureus
ATCC 25923
MRSA Staph.
aureus SA4
E15 E16 E17 E13 Kp1 Kp8 Kp9 Kp5
 2 ± 0 2 ± 0 3 ± 0 2.2 ± 0 1.7 ± 0 2.7 ± 0 1.9 ± 0 3.6 ± 0 ± ± 0 ± 0
 0 0 0 0 2.2 ± 0 ± 1.9 ± 0.1 0 ± ± 0 ±
 0 0 0 0 2 ± 0 ± 2 ± 0 0 2.2± 0 0
 0 0 0 0 0 ± 0 0 ± 0 0
 0 0 0 0 0 0 0 0 0 1.2± 0 0
7a 1.2 ± 0 1.2 ± 0 ±
 0 0 0 0 1.2 ± 0 ± 0 0
7b 3.1 ± 0.1 0 0 2.3 ±
0.1 0 0 0 0 2.2± 0 0
7c ± 0 1.3 ± 0 ± 0 1.7 ± 0 ± 0 ± ±
 0 2.0± 0 0
7d 0 0 0 0 0 0 0 1.03 ± ± ± 0.0 0
7e 0 0 0 0 0 0 0 ± ± ± 0.0 ±
On the other hand, the latter group with quinoline moiety,

  
all tested pathogens (Figure 2). A comparison between cyclic
-amino phosphonate using triphenyl phosphite group and cyclic
-amino phosphonate group bearing quinolone moiety showed
           

di amino propane connected with   
studies stated that   
 Figure 2: Structures of target α -Aminophosphonates.
Copyright@ Ibrahim El Tantawy El Sayed | Biomed J Sci & Tech Res | BJSTR. MS.ID.003936.
Volume 23- Issue 4 DOI: 10.26717/BJSTR.2019.23.003936
17614
Conclusion
     -aminophsophonate was
installed by three one pot reaction of glutaraldehyde, 
        
LiClO   
  Klebsiella pneumonia and
E. coli bacteria.
Acknowledgment
    

Conict of Interest
interest.
References
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            
      


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

6.       

Molecules 11(6): 666-676.
7. 
 
9.        

10. 
11. 
12. 
312.
13.          
acridone and quinoline/quinolone-containing drugs. A critical
       
timeframe in antitumor chemotherapy and treatment of infectious

    
Peña, Leonor Y, et al. (2019) Natural and synthetic quinoline molecules
        
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       



     
        

16. Xi Feng Zhu, Jing Zhang, Shuo Sun, Yan Chun Guo, Shu Xia Cao, et
       
  

17. (1993) Glutaraldehyde Cross-Linking, Fast and Slow Modes Timothy J
A Johnson.

     

19. 
thermal studies of some transition metal complexes of a Schiff base

20.  
       
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21. El GokhaAhmed A, Ghanim Ibrahim MS, Abdel MegeedAhmed El S,
Elkhabiry Shaban, Ibrahim El Tantawy El Sayed (2013) synthesis and


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ISSN: 2574-1241
DOI: 10.26717/BJSTR.2019.23.003936
Ibrahim El Tantawy El Sayed. Biomed J Sci & Tech Res
... The present work has been carried out as part of our ongoing program for developing novel antibacterial agents which are based on α-aminophsophonates. In our previous work, we have reported a new class of cyclic α-aminophophonates bearing quinoline and hydrazine moiety with potent antibacterial activity [26]. These results prompted us to further extend and evaluate their antibacterial activity to understand the mode of action of the active compounds, for example, the determination of DNA gyrase binding affinity as potential inhibitors. ...
... A two series of cyclic diphenylphosphonates (1a-e and 2a-e) were prepared by following the procedure previously reported by us starting from glutaraldehyde, amines, diphenylphosphite, and Lewis acid catalyst. The structures of the synthesized compounds were confirmed based on their spectral data and in good agreement with the proposed structures and with those reported in the literature [26]. The two synthesized series of compounds used for current biological screening are listed in the following Figure 1. ...
... Recently, two series of synthetic chemical compounds (1a-e and 2a-e) were tested against different highly virulent strains of clinical isolates E.coli, K. pneumonia, and Staphylo-Antibiotics 2022, 11, 53 3 of 15 coccus aureus MRSA that previously showed resistance to ciprofloxacin [25,[27][28][29], besides two reference strains (Staphylococcus aureus ATCC 25923, and E. coli ATCC 11229) and exhibited good antibacterial activity [26] as depicted in Figure 2 and Table S1 (cf. supplementary file). ...
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DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC50 of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg2+ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.
... α-Aminophosphonates ( Figure 1) play a crucial role as a platform to design new drugs [13][14][15][16][17][18][19][20]. Among other advantages, there are several reports regarding their antimicrobial activity; alafosfalin, for example, a simple dialkyl α-aminophosphonate, exhibits activity against pathogenic E. coli, S. aureus, Bacillus, and K. pneumonia strains (Figure 1) [21][22][23][24][25][26][27][28][29][30]. However, the application of alafosfalin in medicine is limited due to its instability. ...
... In the absence of enzyme only traces of the target product 1 was formed ( Table 1, entry 1). In addition, four different nonenzymatic catalysts were reported in the literature as sustainable promoters of the Kabachnik-Fields reaction [81][82][83]94,95]; copper(I) iodide, copper(I) oxide, copper(II) acetate, and phenylboronic acid were tested under similar reaction conditions, leading to the target product 1 with up to a 39% yield ( Table 1, entries [19][20][21][22]. It is well recognized that the type of solvent used has a great impact on enzyme stability and activity [84]. ...
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We reported a new method dealing with the synthesis of novel pharmacologically relevant α-aminophosphonate derivatives via a lipase-catalyzed Kabachnik−Fields reaction with yields of up to 93%. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The developed protocol is applicable to a range of H-phosphites and organic amines, providing a wide substrate scope. A new class of α-aminophosphonate analogues possessing P-chiral centers was also synthesized. The synthesized compounds were characterized on the basis of their antimicrobial activities against E. coli. The impact of the various alkoxy groups on antimicrobial activity was demonstrated. The crucial role of the substituents, located at the aromatic rings in the phenylethyloxy and benzyloxy groups, on the inhibitory action against selected pathogenic E. coli strains was revealed. The observed results are especially important because of increasing resistance of bacteria to various drugs and antibiotics.
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Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.
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Green synthesis of a series of novel dialkyl (aryl substituted)(2-fluoro-4-((2-methylcarbamoyl)pyridine-4-yl)oxy)phenyl)amino)methyl)phosphonates is accomplished by a simple and an efficient one pot three component reaction of 3-(4-amino-3-fluorobenzyl)-N-methylbenzamide with different substituted aromatic aldehydes and dialkyl phosphite in the presence of nano Sb2O3 catalyst under solvent free conditions at 40–50 °C to obtain the title compounds. Excellent isolated product yields are obtained (85–95%) with high purity within shorter reaction times (30–60 min). The title compounds are characterized by IR, ¹H, ¹³C, ³¹P-NMR and mass spectral data. The synthesized compounds are screened for their anticell-proliferation activity on seven cell lines, Control cells–HEK293 (human embryonic kidney), DU-145 (human prostate adenocarcinoma), MCF-7 (human ER+/PR+/Her2− breast cancer), MDA-MB-231 (human ER−/PR−/Her2− breast cancer), Mia-Paca-2 (human pancreatic carcinoma), HeLa (human cervical cancer) cells as well as HepG2 (human hepatocellular carcinoma) cancer cell lines using Sulforhodamine B (SRB) assay method. Docking studies were carried out for all these synthesized compounds against topoisomerase-II by using Auto dock method. Doxorubicin was taken as standard. Compounds 4a, 4c, 4d, 4e, 4h, 4i, 4k, and 4l exhibited higher cytotoxic activity than the standard doxorubicin.
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Syntheses of novel N-protected α-aminophosphonates 6 were achieved with high yields through lithium per chlorate catalyzed one-pot three component reaction process. It involves the reaction of aryl substituted Quinoxalinealdehydes, benzyl carbamate, aniline, p-methoxy aniline, p-chloro aniline, p-methyl aniline, propyl amine, pentyl amine, p-amino benzoic acid, 1,4-phenylenediamine, amino uracil, N-glycosyl amine and triphenylphosphite using lithium perchlorate as Lewis acid catalyst in dry dichloromethane at room temperature. A mechanism for this condensation reaction is proposed. Cleavage of the N-phenyloxycarbonyl group under acid hydrolysis afforded the free α-aminophosphonates 8 in quantitative yields. The structures of all new compounds were established by IR, ¹HNMR, 13 CNMR and mass spectral data. All the synthesized compounds were screened for in vitro antibacterial activity and most of them showed potency against both gram positive and gram negative bacteria.
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New generation of copper(II) complexes with α-aminophosphonate as tridentate ligands has been synthesized. It is characterized by elemental analyses, spectral (IR, UV-Vis, MS, EPR, and 1H NMR) studies, thermal analysis as well as magnetic and molar conductance measurements. On the basis of spectral studies, a distorted square planar geometry has been assigned for all the complexes. Specific rotation measurements for both ligands and copper(II) complexes showed that they are enantiomerically enriched. The metal-free ligands and their Cu(II) complexes were tested for their in vitro anticancer activity against human colon carcinoma HT-29 cell lines. The results showed that the synthesized copper(II) complexes exhibited significantly higher anticancer activity than their free ligands. Among all the tested compounds in the series, the complex 5g demonstrated the highest anticancer activity at low micromolar inhibitory concentrations (IC50 = 14.2 µM) which is about a half of the reference drug activity, cisplatin (IC50 = 7.0 µM) in the same assay.
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A simple, efficient, and general method has been developed for the synthesis of various alpha-aminophosphonate derivatives 4a-41 by treatment of substituted benzaldehydes and aniline with bis(2-methoxyethyl)- or bis(2-ethoxyethyl) phosphite under microwave irradiation without solvents and catalysts. The products were characterized by elemental analysis, IR, H-1-N-MR, C-13- and P-31-NMR spectra. The X-ray crystallographic data of the representative compound 41 was determined. The new a-aminophosphonate derivatives were found to possess moderate to good antiviral activity.
Chapter
The recent developments in the use of natural quinoline products and synthetic quinoline-based molecules as antiparasitic agents for Chagas disease (CD), African sleeping sickness (human African trypanosomiasis, HAT), and leishmaniasis (LE) are reviewed in this chapter. Classical and contemporary syntheses of quinoline derivatives are also discussed, paying attention to new green reaction conditions for classical methods such as Skraup and Friedländer syntheses, Doebner reaction or Povarov reaction, among others. Lipinski’s parameters and in silico study are briefly mentioned and applied to some quinolines active against Leishmania and Trypanosoma parasites. This chapter is focused on medicinal chemistry research with natural and synthetic quinoline molecules as antitrypanosomal agents for these parasitic infections. Carefully selected examples are discussed to underline the progress made in the development of natural and synthetic quinolines for potential therapeutic applications in CD, HAT, and LE.
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New α-aminophosphonates bearing 1,2,3-triazolyl moiety were easily synthesized by one-pot reaction of 1-aryl-1H-1,2,3-triazole-4-carbaldehydes, anilines and trimethyl phosphite in good to excellent yields. All the synthesized compounds were characterized by IR, ¹H NMR and ¹³C NMR analysis. These novel 1,2,3-triazole-incorporated α-aminophosphonates may be potential biological compounds due to the presence of both important moieties, 1,2,3-triazole and aminophosphonates. Graphical abstract Open image in new window
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Acridines/acridones, quinolines/quinolones (chromophores) and their derivatives constitute extremely important family of compounds in current medicine. Great significance of the compounds is connected with antimicrobial and antitumor activities. Combining these features together in one drug seems to be long-term benefit, especially in oncology therapy. The attractiveness of the chromophore drugs is still enhanced by elimination their toxicity and improvement not only selectivity, specificity but also bioavailability. The best results are reached by conjugation to natural peptides. This paper highlights significant advance in the study of amino acid or peptide chromophore conjugates that provide highly encouraging data for novel drug development. The structures and clinical significance of amino acid or peptide chromophore conjugates are widely discussed.