Novel organophosphorus compounds as potential antimicrobial agents

Article abstract of DOI:10.1080/10426500701640827

The 4-Thiazolidinone derivatives of phenophosphazines were synthesized by a reaction of Schiff base derivative of phenophosphazine with Thyoglycollic acid in molar ratio of 1:3 using DMF as solvent. Possible structures have been proposed based on elemental analysis, IR and 1H NMR spectral studies. The antibacterial and antifungal activities of these derivatives have been evaluated against pathogens E. coli, S. typhi, S. aureus, B. subtilis, A. niger, and C. Albicans. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701640827

This article was downloaded by: [University of Southern Queensland]
On: 03 October 2014, At: 22:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Novel Organophosphorus
Compounds as Potential
Antimicrobial Agents
S. R. Lokhandwala a & K. R. Desai a
a Department of Chemistry , Veer Narmad South
Gujarat University , Surat, 395 007, India
Published online: 09 May 2008.
To cite this article: S. R. Lokhandwala & K. R. Desai (2008) Novel Organophosphorus
Compounds as Potential Antimicrobial Agents, Phosphorus, Sulfur, and Silicon and the
Related Elements, 183:5, 1264-1271, DOI: 10.1080/10426500701640827
To link to this article: http://dx.doi.org/10.1080/10426500701640827
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.

This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 183:1264–1271, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701640827
Novel Organophosphorus Compounds as Potential
Antimicrobial Agents
S. R. Lokhandwala and K. R. Desai
Department of Chemistry, Veer Narmad South Gujarat University,
Surat 395 007, India
The 4-Thiazolidinone derivatives of phenophosphazines were synthesized by a reac-
tion of Schiff base derivative of phenophosphazine with Thyoglycollic acid in molar
ratio of 1:3 using DMF as solvent. Possible structures have been proposed based on
1
elemental analysis, IR and H NMR spectral studies. The antibacterial and anti-
fungal activities of these derivatives have been evaluated against pathogens E. coli,
S. typhi, S. aureus, B. subtilis, A. niger, and C. Albicans.
Keywords
Antibacterial activity; Antifungal activity; Phenophosphazine;
Thiazolidinone
INTRODUCTION
Phosphorus has important and multifaceted functions in the biochem-
istry of the body. It is ubiquitous in an anatomical term and is of great
importance in a host of reactions throughout virtually all organs and
tissues. The unexpected relationship between the antibacterial activ-
ity and the aggregation behavior in aqueous solution (i.e., lyotropic
liquid-crystalline properties) was revealed through systematic studies
on the antibacterial activity of the phosphonium salts as a novel class of
cationic biocides.1 Organophosphorus compounds are associated with
antiviral,2 anticancer,3 antifungal,4−7 and antibacterial4−7 activities.
These observations encouraged us to synthesize the above derivatives,
as Schiff bases and thiazolidinone derivatives themselves have good
antibacterial and antifungal activities.
RESULTS AND DISCUSSION
2-amino-10-oxo-5,10-dihydro-10λ5-phenophosphazin-10-ol and substi-
tuted aromatic aldehydes were taken in 1:1 molar ratio in presence
Received 29 June 2007; accepted 30 July 2007.
Address correspondence to S. R. Lokhandwala, Department of Chemistry, Veer
Narmad South Gujarat University, Surat 395 007, India. E-mail: snehal sl@yahoo.co.in
1264

Novel Organophosphorus Compounds
1265
of methanol as solvent to yield 2-[(substituted benzylidene)-amino]-
10-oxo-5,10-dihydro-10-λ5-phenophosphazin-10-ol which was subse-
quently reacted with Thyoglycollic acid in molar ration of 1:3
using DMF as solvent to give corresponding 3-(10-hydroxy-10-
oxo-5,10-dihydro-10λ5-phenophosphazin-2-yl)-2-(substituted phenyl)-
thiazolidin-4-one (Scheme 1). Physical and analytical details of the com-
pounds are given in Table I.
SCHEME 1
IR SPECTRA
The formation of Schiff base derivatives was identified by the disappear-
ance of ν (N H) absorption band at 1250–1340 cm−1 and thiazolidinone
derivatives were identified by the disappearance of ν (C N) stretch-
ing vibration at 1595–1610 cm−1 present in monoamino and Schiff base
derivatives respectively. Moreover the ν (C O) stretching vibration
was observed at 1710–1750 cm−1. The ν (C-S-C) stretching vibration
and was observed at 700–750 cm−1, which proves thiazolidinone nu-
cleus. In phenophosphazine derivatives characteristic stretching vibra-
tion ν (P O)8 appeared at 1240–1250 cm−1and ν (P OH)9 appeared
at 910–1040 cm−1 (Table II).
NMR SPECTRA
1H NMR spectra of 2-[(substituted benzylidene)-amino]-10-oxo-5,10-
dihydro-10-λ5-phenophosphazin-10-ol showed a benzylideneimine pro-
ton signal at δ 8.35 as singlet, which disappeared in thiazolidinone

1266

1267

1268

Novel Organophosphorus Compounds
1269
derivative. Instead of that, a characteristic proton signal at δ 5.90 ap-
peared showing the presence of N CH group. A proton signal at δ 2.0
was observed as singlet in each compound confirming the presence of
P OH. The other signals were observed in accordance with the sub-
stituent groups and confirming their presence which are summarized
in Table IV.
TABLE IV Assignment of Main 1H NMR Bands (δ) of Thiazolidinone
Derivatives of Phenophosphazine Compounds
Comp.
no.
Molecular formula
R
Assignments (δ)
SN-01 C22H19O4N2PS
4-OCH3
3.8(s,1H,N-H);1.9(s,1H,P-OH);
5.90(s,1H,N-CH);3.37(d,2H,C-CH2);
3.71(t,3H,C-OCH3); 6.5–7.0(m,11H,
Aromatic)
SN-02 C21H16O3N2PClS 3-Cl
3.6(s,1H,N-H);2.0(s,1H,P-OH);
5.91(s,1H,N-CH);3.36(d,2H,C-CH2);
6.5–7.08(m,11H,Aromatic)
SN-03
SN-04
C
21H16O3N2PBrS 3-Br
3.7(s,1H,N-H);1.8(s,1H,P-OH);
5.88(s,1H,N-CH);3.40(d,2H,C-CH2);
6.5–7.24(m,11H,Aromatic)
3.8(s,1H,N-H);1.8(s,1H,P-OH);
5.95(s,1H,N-CH);3.39(d,2H,C-CH2);
7.59(s,1H,C-CH); 6.5–7.65(m,12H,
Aromatic)
C23H19O3N2PS
CH=CH
SN-05
SN-06
C
21H16O5N3PS
27H21O4N2PS
2-NO2
3.65(s,1H,N-H);1.7(s,1H,P-OH);
5.92(s,1H,N-CH);3.36(d,2H,C-CH2);
6.5–8.07(m,11H,Aromatic)
3.8(s,1H,N-H);1.9(s,1H,P-OH);
5.90(s,1H,N-CH);3.37(d,2H,C-CH2);
6.5–7.21(m,16H,Aromatic)
C
3-OC6H5
SN-07 C23H21O5N2PS
3-OC2H5 4-OH 3.7(s,1H,N-H);2.0(s,1H,P-OH);
5.91(s,1H,N-CH);3.37(d,2H,C-CH2);
3.96 (d,2H,C-CH2); 4.9(s,1H,C-OH);
1.32(t,3H,C-CH3);6.5–7.0(m,9H,
Aromatic)
SN-08
C22H19O5N2PS
3-OCH3 4-OH
3.6(s,1H,N-H);1.9(s,1H,P-OH);
5.90(s,1H,N-CH);3.37(d,2H,C-CH2);
3.72(t,3H,C-OCH3);5.1(s,1H,C-OH);
6.5–7.2(m,9H,Aromatic)
SN-09 C21H17O3N2PS
H
3.8(s,1H,N-H);1.7(s,1H,P-OH);
5.93(s,1H,N-CH);3.37(d,2H,C-CH2);
6.5–7.14(m,12H,Aromatic)
SN-10
C23H21O6N2PS
3,5-OCH3 4-OH 3.7(s,1H,N-H);1.9(s,1H,P-OH);
5.90(s,1H,N-CH);3.37 (d,2H,C-CH2);
3.74(t,3H,C-OCH3);4.7(s,1H,C-OH);
6.5–7.1(m,8H,Aromatic)

1270
S. R. Lokhandwala and K. R. Desai
ANTIMICROBIAL ACTIVITY
Antimicrobial activity was carried out for the synthesized test com-
pounds using Agar Cup method10,11 which used Mueller-Hinton agar
and Sabouraud Dextrose agar (pH-7.3
0.2 at 25◦C) for bacterial
and fungal activity respectively and a dose of 50 ppm. Results of the
antibacterial and antifungal activities measured as zone of inhibi-
tion (mm) for thiazolidinone derivatives of phenophosphazines against
S aureus and B Subtilis (gram positive bacteria), E coli and S Ty-
phi (gram negative bacteria), Candida albicans and Aspergillus niger
(fungus) are summarized in Table III. The antimicrobial activities
of these compounds were found to be exceeding than the correspond-
ing Schiff base12 derivatives of phenophosphazine. These compounds
were compared to commercial antibacterial and antifungal drugs like
Streptomycin and Cotrimazole. Among all the compounds, the antibac-
terial activity against B Subtilis was more prevalent. Compound SN-09
showed promising activity against S Aureus (50%) and Compound SN-
06 showed promising activity against B Subtilis (68.3%), E coli (40%),
S Typhi (60%), C albicans (50%) and A niger (37.1%) respectively as
compared to the standard drugs.
EXPERIMENTAL
All commercial reagents and solvents were dried and distilled by com-
mon methods before use. Melting points were determined by capillary
method and are uncorrected. The operations involving phosphorus com-
pounds were carried out in dry equipment in nitrogen atmosphere. IR
spectra were recorded on Perkin-Elmer 577 grating spectrometer in
KBr discs in the region of 4000-200 cm−1. NMR were recorded on JEOL
FX-90Q spectrophotometer using CDCl3 as solvent.
Synthesis of 3-(10-hydroxy-10-oxo-5,10-dihydro-10λ5-
phenophosphazin-2-yl)-2-(substituted phenyl)-
thiazolidin-4-one
In a 250 ml round bottom flask, 2-[(4ꢀ-methoxy-benzylidene)-amino]-
10-oxo-5,10-dihydro-10-λ5-phenophosphazin-10-ol ( 3.6433 g, 10 mmol)
and thioglycolic acid ( 2.76 g, 30 m mol) were dissolved in DMF (60 ml)
as a solvent. The reaction mixture was refluxed for 10–12 h. Excess
of solvent was then removed by distillation and cooled. The solid thus
separated was filtered, washed, dried, and recrystallized with glacial
acetic acid. The process was repeated using different substituted Schiff
bases (10 mmol) to obtain different compounds.

Novel Organophosphorus Compounds
1271
CONCLUSION
It can be concluded from the above synthetic work that phosphorus
if incorporated with the standard antimicrobial agents may enhance
their activities. The results at primitive stage are satisfactory and it
may be thought that phosphorus- containing antimicrobials may cover
the broad spectrum in antimicrobial world.
REFERENCES
[1] A. Kanazawa and T. Ikeda, Coordination Chem Reviews, 198(1), 117–131 (2000).
[2] S. S. Kadam, K. R. Mahadik, and K. G. Bothara, Principles of Medicinal Chem, I,
132 (2000).
[3] S. S. Kadam, K. R. Mahadik, and K. G. Bothara, Principles of Medicinal Chem, I,
154 (2000).
[4] A. Bijul Lakshman and R. L. Gupta, Indian J of Chem, 44B, 152–157 (2005).
[5] P. Vasu Govardhana Reddy, C. Suresh Reddy, and M. Venugopal, J. of Heteroatom
Chem, 14(6), 509–512 (2003).
[6] K. Demarest, C. Shwender, and D. Wustrow, U.S. Patent, 5, 532, 226 (1996).
[7] M. F. Pharanath, S. Babu, U. Anasuyamma, C. Naga Raju, and C. Suresh Reddy,
J Heteroatom Chem, 16(7), 572–575 (2005).
[8] N. Kabra, V. Gupta, V. Kabra, S. Jain, and K. Bhatanagar, Phosphorus, Sulfur and
Silicon, 178, 851 (2003 ).
[9] B. Silverstein, G. Bassler, and T. Morril, Spectrometric identification of organic com-
pounds IV, 176 (1963).
[10] S. C. Prescott and C. G. Dunn , Industrial Microbiology, 519 (1949).
[11] W. Burrow, Textbook of Microbiology, 8 (1954).
[12] A. K. Mittal and U. P. Singhal, J Indian Chem Soc, LIX, 373 (1982).