Synthesis and antibacterial activity of 2,4,6-tri substituted s-triazines

Article abstract of DOI:10.1016/j.bmcl.2004.12.020

Various 2,4,6-tri substituted s-triazines were synthesized and screened for antibacterial activity against Gram-positive and Gram-negative organisms. These s-triazine derivatives displayed high in vitro antibacterial activities comparable to penicillin an

Full text of DOI:10.1016/j.bmcl.2004.12.020

Bioorganic & Medicinal Chemistry Letters 15 (2005) 1121–1123
Synthesis and antibacterial activity of
2,4,6-tri substituted s-triazinesq
K. Srinivas,a,b U. Srinivas,a V. Jayathirtha Rao,a,* K. Bhanuprakash,b,*
K. Hara Kishorec and U. S. N. Murtyc,*
aOrganic Chemistry Division II, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
bInorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
cBiology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
Received 13October 2004; accepted 6 December 2004
Available online 29 December 2004
Abstract—Various 2,4,6-tri substituted s-triazines were synthesized and screened for antibacterial activity against Gram-positive and
Gram-negative organisms. These s-triazine derivatives displayed high in vitro antibacterial activities comparable to penicillin and
streptomycin against tested microorganisms.
Ó 2004 Elsevier Ltd. All rights reserved.
Substituted s-triazine derivatives are an important class
of compounds having anticancer,1 antitumor,2 antiviral3
and antifungal4 activities. These compounds have been
used in the treatment of depression,5 and hence received
a considerable therapeutic importance. These are valu-
able bases for estrogen receptor modulators6a and also
used as bridging agents to synthesize herbicides.6b Fur-
ther substituted s-triazines have been used as NLO
materials, which have a wide range of applications in
optoelectronics and telecommunications.7 Research on
new substances possessing antibacterial activity has con-
siderable attention owing to the continuous increase in
bacterial resistance.8 It has been reported that substi-
tuted s-triazine derivatives possess antibacterial activ-
ity.4,9 In this article, we illustrate the synthesis and
antibacterial activity of a series of s-triazine derivatives.
Synthesis of various 2,4,6-tri substituted s-triazines is
illustrated in Schemes 1–3. Compounds 1–5 were syn-
thesized by allowing reaction between benzyl alcohol
R
R
CH2OH
O
N
O
O
Cl
N
Cl
NaOH / solvent
+
N
N
R
N
N
R
Cl
1: R = H
2: R = Cl
3: R = F
4: R = CH3
5: R = OCH3
Scheme 1.
Keywords: s-Triazines; Synthesis; Antibacterial activity; Antifungal activity.
q Communication No. 041208.
*
Corresponding authors. Tel.: +91 40 27193933; fax: +91 40 27160757 (V.J.R.); e-mail: jrao@iict.res.in
0960-894X/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2004.12.020

1122
K. Srinivas et al. / Bioorg. Med. Chem. Lett. 15 (2005) 1121–1123
subtilis (MTCC 441), Bacillus sphaericus (MTCC 11)
R
Staphylococcus aureus (MTCC 96) and three Gram-neg-
ative organisms viz. Chromobacterium violaceum
(MTCC 2656), Klebseilla aerogenes (MTCC 39), Pseudo-
monas aeruginosa (MTCC 741) by broth dilution meth-
od recommended by National Committee for Clinical
Laboratory (NCCL) standards.12
CH2CN
N
Triflic acid
N
N
R
R
6: R = H
7: R = Cl
8: R = OCH3
Standard antibacterial agents like penicillin and strepto-
mycin were also screened under identical conditions for
comparison. The minimum inhibitory concentration
(MIC) values are presented in Table 1. It has been ob-
served that the test compounds (1–13) exhibited interest-
ing antibacterial activity, however with a degree of
variation. The compound 6, benzyl substituted triazine,
without any substituent at the para position of the aryl
group exhibited remarkable antibacterial activity
against tested organisms comparable to reference agents
penicillin and streptomycin. Replacement of hydrogen
at the para position of the aryl group in benzyl substi-
tuted triazines by chloro and methoxy function (7 and
8) exhibited moderate activity compared to 6. Among
the benzyloxy substituted triazines, 1, 2 and 3 (Table
1) displayed moderate activity. Improved activity
against Chromobacterium violaceum is observed by
the introduction of methoxy function in benzyloxy tri-
azine at para position, 5 (Table 1). Methyl derivative
R
Scheme 2.
derivative and cyanuric chloride in the presence of base
(Scheme 1).10 Compounds 6–8 were synthesized using
trimerization reaction of phenyl acetonitrile derivative
with the use of triflic acid (Scheme 2). Compounds 9–
13 were synthesized by treating cyanuric chloride with
corresponding bezylamine in the presence of K2CO3
and 18-Crown-6 as a catalyst in dry toluene (Scheme
3).11 All compounds were purified by column chroma-
tography followed by recrystallization.
The minimum inhibitory concentrations (MIC) of vari-
ous substituted s-triazines were tested against three
representative Gram-positive organisms viz. Bacillus
R
R
CH2NH2
H
N
N
NH
Cl
N
Cl
K2CO3 / solvent
18-Crown-6
+
N
N
R
N
N
HN
R
Cl
9: R = H
10: R = Cl
11: R = F
12: R = CH3
13: R = OCH3
Scheme 3.
Table 1. In vitro antibacterial activity of 2,4,6-tri substituted s-triazines
Compd. no.
MIC, lg/mL
Gram-positive organism
Gram-negative organism
B. subtilis
B. sphaericus
S. aureus
C. violaceum
K. aerogenes
P. aeruginosa
1
25
25
25
25
25
—
25
—
—
2
12.5
25
12.5
12.5
—
12.5
25
3
12.5
—
25
—
—
—
4
—
25
—
25
5
25
6.25
25
6.25
6.25
25
25
—
—
6
12.5
25
12.5
25
6.25
25
25
7
—
—
8
50
25
12.5
25
25
25
25
25
9
10
25
—
—
—
—
—
25
50
—
—
25
—
11
12
—
—
—
—
—
25
50
—
25
—
25
13
Penicillin
Streptomycin
12.5
3.125
12.5
25
—
12.5
3.125
1.562
6.25
1.562
6.25
12.5
3.125
6.25
1.562

K. Srinivas et al. / Bioorg. Med. Chem. Lett. 15 (2005) 1121–1123
1123
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In conclusion, a series of 2,4,6-tri substituted s-triazines
were synthesized and evaluated for antibacterial activity.
Most of the compounds showed antibacterial acti-
vity. Among them 6 exhibited the most significant acti-
vity whereas 2, 5, 9 and 13 were displayed moderately
large activity against both Gram-positive and Gram-
negative microorganisms. Least activity was observed
for triazine with benzylamine derivatives.
Acknowledgements
We thank Dr. J. S. Yadav, Director IICT and Head of
the Division for the encouragement. K.S. and U.S.
thank to CSIR-New Delhi and University Grants Com-
mission-New Delhi for fellowship.
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