Synthesis, photophysical, antibacterial and larvicidal studies on triazolophanes with 5-nitro isophthalate functionality at the intraannular position

Article abstract of DOI:10.1039/c8nj01248b

1 : 1 and 2 : 2 oligomeric triazolophanes with 5-nitro isophthalate and triazolyl functionalities at the intraannular position have been synthesized by copper(i) catalyzed 1,3 dipolar cycloaddition of the corresponding propargylic esters with various phen

Full text of DOI:10.1039/c8nj01248b

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Synthesis, photophysical, antibacterial and
larvicidal studies on triazolophanes with 5-nitro
isophthalate functionality at the intraannular
position†
Cite this:DOI: 10.1039/c8nj01248b
Sivasamy Selvarani,a Perumal Rajakumar, *a Subramani Nagaraj,b
Manisha Choudhuryc and Devadasan Velmuruganc
1 : 1 and 2 : 2 oligomeric triazolophanes with 5-nitro isophthalate and triazolyl functionalities at the
intraannular position have been synthesized by copper(I) catalyzed 1,3 dipolar cycloaddition of the
corresponding propargylic esters with various phenyl substituted aliphatic azides under mild conditions
through click methodology. The 1 : 1 oligomeric triazolophanes exhibit good target binding ability and better
antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Salmonella typhi and Escherichia coli
bacteria than the 2 : 2 oligomeric triazolophanes, supported by molecular docking studies, and triazolophanes
T3, T4 and T5 show good larvicidal activity.
Received 13th March 2018,
Accepted 19th June 2018
DOI: 10.1039/c8nj01248b
rsc.li/njc
simple and regioselective.11 Click chemistry12 has been exten-
sively applied in many fields such as antibacterial polymers,13
Introduction
Over the past few decades, the synthesis of bioactive macro- dyes,14 corrosion inhibitors,15 drugs,16 photo stabilizers17 and
cycles with 1,2,3-triazole ring systems has generated great photographic materials. The synthesis of supramolecular archi-
interest from researchers due to their excellent optoelectronic tectures such as dendrimers18 and cyclophanes19 with a triazole
and biological activities.1 Triazolophane motifs can be embedded unit is of interest due to their biological applications. Macro-
between two or more active residues, which can function as cycles having ester and phenolic functionalities show
multiple targets due to their improved lipophilicity, membrane antibacterial,20 antioxidant and larvicidal activity. Moreover,
penetration, metabolic stability, solubility, and oral bio- some of the ester macrocycles show larvicidal activity against
availability.2,3 Triazole containing macrocycles exhibit various the larvae of Aedes aegypti mosquitoes.21
applications in many fields such as host–guest complexation,
Though naturally occuring22 and synthetic23 aromatic esters
molecular recognition,4 antibacterial,5 antifungal,6 antiviral, are used as fragrant materials, such as fructone and ethyl
anti-inflammatory, anti-cancer,7 larvicidal8a and antimalarial methyl phenyl glycidate, they are also used as drug materials,
activities.8b
Triazoles can function as biological linkers and as bridging
such as benzyl benzoate, pivampicillin etc.
The biological significance of aromatic nitroesters with
units in supramolecular architectures which exhibit chemical triazole functionality prompted us to synthesize the new class
stability under physiological conditions.9 Moreover, triazoles of triazolophanes 1–10 (Fig. 1) and explore their photophysical,
play a crucial role in the field of pharmaceutical chemistry antibacterial and larvicidal activity.
because of their ability to form hydrogen bonding, which is
essential for their solubility and biological activity.10 Triazoles
can be generated by click methodology which is highly reliable,
Result and discussion
Triazole based macrocycles
a Department of Organic Chemistry, University of Madras, Maraimalai (Guindy)
Triazole based macrocycles 1–10 (Fig. 1) can be synthesized
from the corresponding bispropargyloxy ester functionalized
precyclophane. The required bispropargyloxy precyclophanes
can be obtained from 5-nitro isophthalic acid and propargyl
alcohol. Click reaction is a novel approach for the synthesis of
prospective drugs from alkynes and azides. From this point of
view, we have synthesized the ester based triazolophanes 1–10,
Campus, Chennai–600 025, India. E-mail: perumalrajakumar@gmail.com;
Fax: +91 44 235 2494; Tel: +91 44 22202810
b Centre for Advanced Studies in Botany, University of Madras,
Maraimalai (Guindy) Campus, Chennai–600 025, India
c CAS in Crystallography and Biophysics, University of Madras,
Maraimalai (Guindy) Campus, Chennai–600 025, India
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8nj01248b
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Fig. 1 Molecular structure of 1 : 1 (1–5) and 2 : 2 (6–10) oligomeric triazolophanes.
from the bispropargyloxy precyclophane esters and the corres- 2,7-diol 14, and 1,4-dihydroxybenzene 15 with 4.0 equiv. of
ponding aryl alkyl azides 21, 22, 23, 24 and 25, which in turn 1,4-dibromobutane 26 in acetone and in the presence of
can be obtained from the corresponding bisbromides and 3.0 equiv. potassium carbonate at 60 1C for 7 h (Scheme 1).
sodium azide.
The 1H NMR spectrum of E-1-(2,4-bis(4-bromobutoxy)phenyl)-
2-(4-nitrophenyl)diazene 16 showed bromomethylene and
O-methylene protons as a triplet at d 3.51 and 3.58, and 4.09
Synthesis and characterization of the triazolophanes
The bisbromides 16, 17, 18, 19 and 20 were obtained in 69%, 79%, and 4.23 in addition to the signals for the other aliphatic and
72%, 78% and 75% yields, respectively by the reaction of 1.0 equiv. aromatic protons. The 13C NMR spectrum of E-1-(2,4-bis-
of each of the diols viz E-4-((4-nitrophenyl)diazenyl)benzene-1,3-diol (4-bromobutoxy)phenyl)-2-(4-nitrophenyl)diazene 16 displayed
11, methyl 3,5-dihydroxybenzoate 12, Resorcinol 13, naphthalene- signals for the bromomethylene and O-methylene carbons
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Scheme 1 Reagents and conditions: (i) K2CO3 (3.0 equiv.), acetone (dry), 12 h. 16 (69%); 17 (79%); 18 (72%); 19 (78%); 20 (75%). (ii) NaN3 (2.2 equiv.),
acetone : H2O (3 : 1, 40 mL), 60 1C, 12 h. reflux. 21 (77%); 12 (79%); 13 (71%); 14 (75%); 25 (81%).
at d 33.2, 33.5 and 67.4, 68.7 in addition to the signals of the two signals for the azidomethylene and O-methylene carbons at d
aliphatic carbons and ten aromatic carbons. In the mass spec- 55.4, 55.8 and 65.4, 65.9 in addition to the signals for the other
trum the appearance of a molecular ion peak at m/z 527 [M+] also aliphatic carbons and for the ten aromatic carbons. In the
confirmed the structure of E-1-(2,4-bis(4-bromobutoxy)phenyl)-2- mass spectrum the appearance of the molecular ion peak
(4-nitrophenyl)diazene 16. Furthermore, the elemental analysis at m/z 453 [M+] also confirmed the structure of E-1-(2,4-bis(4-
also supported the composition of E-1-(2,4-bis(4-bromobutoxy)- azidobutoxy)phenyl)-2-(4-nitrophenyl)diazene 21. Furthermore, the
phenyl)-2-(4-nitrophenyl)diazene 16.
elemental analysis also supported the composition of E-1-(2,4-
Similarly, the structure of the bisbromides 17, 18, 19 and 20 bis(4-azidobutoxy)phenyl)-2-(4-nitrophenyl)diazene 21. Similarly,
was also confirmed from spectral and analytical data. The the structure of the bisazides 22, 23, 24 and 25 was also confirmed
reaction of 1.0 equiv. of each of the bisbromides 16, 17, 18, from spectral and analytical data as shown in the ESI† (Fig. S5, S6,
19 and 20 with 2.2 equiv. of sodium azide in acetone : water S9, S10, S13 and S14).
(3 : 1, 40 mL) at 60 1C for 12 h afforded the corresponding aryl
alkyl azides 21, 22, 23, 24 and 25 in 77%, 79%, 71%, 75% and phanes 1, 2, 3, 4 and 5 and 2 : 2 oligomeric triazolophanes 6, 7,
81% yields, respectively (Scheme 1). 8, 9 and 10 is shown in Scheme 2. The reaction of 4.0 equiv. of
The synthesis of the ester based 1 : 1 oligomeric triazolo-
In the 1H NMR spectrum E-1-(2,4-bis(4-azidobutoxy)phenyl)- propargyl alcohol with one equiv. of 5-nitroisophthaloyl chloride
2-(4-nitrophenyl)diazene 21 showed azidomethyene and afforded the precyclophane ester 27 as reported earlier from our
O-methylene protons as triplets at d 3.32 and 3.35, and 4.01 laboratory.20 The reaction of 1.0 equiv. of bispropargyl-5-nitro
and 4.14 in addition to the signals for the other aliphatic and isophthalate 27 with 1.0 equiv. of each of the bisazides 21, 22,
aromatic protons. The 13C NMR spectrum of E-1-(2,4-bis- 23, 24 and 25 in the presence of CuSO4Á5H2O (10 mol%), sodium
(4-azidobutoxy)phenyl)-2-(4-nitrophenyl)diazene 21 displayed ascorbate (10 mol%) in a mixture of THF–water (3 : 1) at room
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Scheme 2 Reagents and conditions: (i) CuSO4Á5H2O (10 mol%), sodium ascorbate (10 mol%) THF–H2O (3 : 1), rt, 12 h. 1 (32%); 2 (25%); 3 (38%); 4 (29%);
5 (32%); 6 (30%); 7 (28%); 8 (30%); 9 (25%); 10 (33%).
temperature for 12 h afforded the corresponding 1 : 1 triazolophanes N-CH2, the O-CH2 protons appeared as a triplet at d 4.52, 4.56,
1, 2, 3, 4 and 5 in 32%, 25%, 38%, 27% and 32% yields and the and the triazolyl proton appeared as a singlet at 7.78, in
same reaction also provided the 2 : 2 oligomeric triazolophanes 6, 7, addition to the signals for aromatic protons. The 13C NMR
8, 9 and 10 in 30%, 28%, 30%, 25% and 33% yields, respectively spectrum of the 2 : 2 oligomeric triazolophane 6 showed signals
(Scheme 2). The 1 : 1 and 2 : 2 oligomeric triazolophanes can be at d 26.0, 27.0, 50.1, 59.0, 67.4, 68.7 and 128.4 for aliphatic
easily separated by column chromatography on silica gel with methylene, N-methylene, O-CH2 and triazole carbon, in addi-
CHCl3 : methanol (3 : 1) as the eluent for 1 : 1 and CHCl3 : methanol tion to the other signals for the aromatic carbons. The mass
(4 : 1) as the eluent for 2 : 2 oligomeric triazolophanes.
spectrum of the 2 : 2 oligomeric triazolophane 6 showed the
The 1H NMR spectrum of 1 : 1 oligomeric ester function- molecular ion peak at m/z 1481 [M + H+]. Similarly, the structure
alized triazolophane 1 displayed two sharp singlets at d 1.85, of the 2 : 2 oligomeric cyclophane esters 7, 8, 9 and 10 was
2.09 for aliphatic protons, the O-methylene protons appeared as characterized from spectral and analytical data as shown in the
a singlet at d 4.43, 5.49, the N-methylene protons appeared as a ESI† (Fig. S16).
doublet at d 4.05, and the triazole proton appeared as a singlet
Photophysical studies on the 1 : 1 and 2 : 2 oligomeric
triazolophanes
at d 7.66 in addition to the signals for the aromatic protons. The
13C NMR spectrum of the 1 : 1 oligomeric triazole macrocycle 1
showed five signals at d 24.8, 26.4, 58.1, 66.5 and 68.2 for the The UV-vis absorption spectra of triazolophanes 1–10 were
aliphatic methylene, N-methylene, and O-methylene carbons recorded in DCM at a concentration of 1 Â 10À5 M and the
and the triazolyl carbon appeared at d 127.7 in addition to the lmax values are summarized in Table 1. All the triazolophanes
signals for the aromatic carbons. From the appearance of a showed two absorption bands between 239 and 399 nm in the
molecular ion peak at m/z 741 [M + H+] and also from the absorbance spectrum (Fig. 2a and b) except for the cyclophanes
elemental analysis the structure of the macrocyclic ester 1 was 4 and 9 which showed an absorbance band at 241–242 nm.
confirmed. Similarly, the structure of the 1 : 1 oligomeric tri- The absorption maximum between 239 and 251 nm for all the
azole macrocycles 3, 4 and 5 was confirmed from spectral and cyclophanes could be due to the p–p* transition and the
analytical data as shown in the ESI† (Fig. S15).
absorption maximum at higher wavelengths between 289 and
The 1H NMR spectrum of 2 : 2 oligomeric triazolophane 6 399 nm could be due to the n–p* transition. However, the
showed a triplet at d 4.02, 4.16 for the eight protons of the triazolophanes 1 and 6 showed a strong absorption band
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Table 1 UV-Vis spectral data of the nitroester based triazolophanes 1–10
Triazolophanes labs max (nm) O.D.
e (mol LÀ1 cmÀ1) Â 105
1
2
3
4
5
6
7
8
9
10
239, 397
242, 291
251, 306
241
242, 295
242, 399
241, 289
251, 305
242
0.43, 0.54 4.3, 5.4
1.57, 0.55 1.6, 5.5
1.35, 0.36 1.4, 3.6
0.70
7.0
0.75, 0.23 7.5, 2.3
0.74, 0.95 7.4, 9.5
1.95, 0.66 1.9, 6.6
1.74, 0.43 1.7, 4.3
1.05
1.1
241, 306
1.02, 0.27 1.0, 2.7
between 397 and 399 nm assigned to the n–p* transitions of the
azobenzene chromophore.
Fig. 3 Photoisomerisation of triazolophane 1 irradiated at 365 nm by a UV
lamp in CHCl3 (1 Â 10À5 M) solution.
Photoisomerisation studies
The azobenzene chromophore shows photoinduced, reversible
cis/trans isomerisation. The photoinduced trans to cis isomer-
isation behavior of dendrimers 1 and 6 was investigated by
UV-vis spectrophotometry. The triazolophanes 1 and 6 were
irradiated at 365 nm to induce trans–cis isomerisation. Fig. 3
shows the photoisomerisation of triazolophane 1 on UV
irradiation. Photo irradiation of the azodendrimers at the
concentration of 1 Â 10À5 M using 365 nm in CHCl3 results
in a decrease in the intensity of the absorbance at 398 nm and
increases the intensity of the band at 318 nm, which is assigned
to trans–cis photoisomerisation.
Triazolophane 1 undergoes trans–cis isomerisation as revealed
by the decrease in the absorbance for the trans isomer and
increase in the absorbance of the cis isomer. The isosbestic
point was observed at 318 nm and the system needs 12 minutes
to attain the photostationary state.
antibacterial agents are better than the natural ones because
of the possibility to overcome the drug resistance and improve
the antibacterial activity by structural modifications. Ester
based piperazinophanes against Escherichia coli, Klebsiella
pneumoniae, Staphylococcus aureus and Staphylococcus pyogens
bacteria have been reported from our laboratory earlier20 and
the reported piperazinophanes have shown remarkable anti-
bacterial activity against Escherichia coli and Staphylococcus aureus.
Ester functionalized 1,4-disubstituted 1,2,3-bistriazole24 shows
good antibacterial activity against Escherichia coli. The in vitro
antibacterial activity of the synthesized novel triazole based cyclo-
phanes T1 (triazolophane 1) to T10 (triazolophane 10) was
screened by a well diffusion assay.25 The four test bacterial strains
Staphylococcus aureus (MTCC96), Bacillus subtilis (MTCC441),
Salmonella typhi (ATCC 6539) and Escherichia coli (MTCC 1698)
were selected for the antibacterial activity study and compared
with commercial antibiotic cefotaxime. Table 2 shows the dia-
meter of the zone of inhibition around the disk expressed in
millimeters (mm) for all synthesized triazolophanes 1–10 against
the bacterial strains with tetracycline as the standard. Triazolo-
phanes T3 and T5 showed the highest inhibition zones for both
Antibacterial activity
Bacterial infection is a worldwide health issue due to the
resistance of microorganisms to the existing drugs. Hence, there
is an urgent need to find new antibacterial drugs which would
exhibit bactericidal and bacteriostatic activity. The synthetic
Fig. 2 UV-Vis spectra of (a) 1 : 1 oligomers 1–5 and (b) 2 : 2 oligomers 6–10 at a concentration of 1 Â 10À5 in dichloromethane at room temperature.
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Table 2 In vitro antibacterial activity of the synthesized triazolophanes 1–10 at 50, 75 and 100 mg mLÀ1 by well diffusion assay
Zone of inhibition (mm)
Gram positive bacteria
Gram negative bacteria
Staphylococcus aureus (MTCC96)
Bacillus subtilis (MTCC441)
Salmonella typhi (ATCC6539)
Escherichia coli (MTCC1689)
Triazolophanes
A
b
c
d
a
b
c
d
a
b
c
d
a
b
c
d
1
2
3
4
5
6
7
8
12
—
16
—
17
12
—
—
—
12
—
15
10
17
13
19
13
9
16
13
21
15
22
15
11
8
17
15
23
19
25
17
13
15
13
19
—
10
12
19
10
17
13
11
12
10
10
—
11
13
21
14
23
11
15
14
12
11
—
12
15
24
17
25
15
17
18
15
14
—
29
24
27
20
29
17
29
28
24
22
—
13
—
17
—
19
—
—
—
—
—
—
16
—
19
10
21
—
9
—
—
—
—
15
15
21
12
24
10
14
11
9
18
17
24
20
26
18
15
13
12
18
—
10
—
13
—
10
—
—
—
—
—
—
12
12
15
—
13
—
7
—
—
—
—
13
14
17
—
15
12
12
12
12
12
—
19
20
22
23
24
19
20
19
20
14
—
7
9
10
Control
—
13
—
11
14
—
13
—
Note: a = 50 mg mLÀ1 of sample; b = 75 mg mLÀ1 of sample; c = 100 mg mLÀ1 of sample; d = standard drug (30 mg mLÀ1 of cefotaxime).
Gram positive and Gram negative pathogenic bacteria compared
From GLIDE XP docking, out of ten ligands, only four
to T1, T2 and T4. The 2 : 2 oligomeric triazolophane T6 showed ligands T2, T3, T4 and T5 showed interaction with the target
better antimicrobial activity towards the Gram positive micro- protein (Table 3). The remaining compounds did not show
organisms, viz. Staphylococcus aureus (MTCC96) and Bacillus sub- encouraging results in docking due to the incompatibility of
tilis (MTCC441), than the Gram negative bacteria, viz. Escherichia the structures with the active site. Furthermore, an induced fit
coli (MTCC 1698) and Salmonella typhi (ATCC 6539). The triazole docking study was carried out for the compounds T3 and T5
based 2 : 2 oligomeric cyclophanes T7, T8, T9 and T10 also which showed comparable glide energy and docking score to
inhibited the antibacterial activity to some extent in most of the the reference inhibitor cefotaxime (Table 4). The compounds
tested concentrations. In conclusion, all the synthesized com- show a considerable number of both hydrogen bond and
pounds particularly T3, T4, T5 and T6 have increased antibacterial hydrophobic interactions with the active site residues.
activity against all the selected human pathogenic bacteria. The
Compound T3 showed interactions with the key residues
triazolophanes T3, T4, T5 and T6 may be developed further as Asn104 and Asn132 with a binding energy of À46.05 kcal molÀ1
antibacterial drugs as they exhibit better antibacterial activity and a glide score of À5.27 in comparison with cefotaxime
against the tested pathogens than all the other compounds with a binding energy of À69.33 kcal molÀ1 and glide score
including cefotaxime. However, further studies are required to of À8.07 kcal molÀ1 respectively as evident from Fig. 4. The
determine their mode of action and their potential application compound T5 showed hydrogen bond interaction with the
against a wide range of human pathogens. Dimethyl sulfoxide was residues Asn132 and Asn104 with a glide score of À4.74 and
used as the control which showed nil activity with reference to all glide energy of À52.30 kcal molÀ1 as shown in the ESI.†
the tested bacteria.
Structure activity relationship studies
Molecular docking
Based on the structure of the triazolophanes the in vitro anti-
The molecular docking study was carried out to analyze the
bacterial activity revealed that the triazolophanes T2, T3 and T5
binding affinity of the test compounds with the target protein
having triazoles with ester moieties show better activity as com-
CTXM-enzyme in complex with cefotaxime (PD ID: 3HLW). In
pared to the other cyclophanes as they can interact with bacteria
Gram-negative bacteria, the production of b-lactamases is the
through van der Waals and hydrophobic interactions. Moreover,
main cause of resistance to b-lactam antibiotics. b-Lactamases
1,2,3-triazole has rigidifying nature, which can improve their
cleave the amide bond in the b-lactam ring and makes b-lactam
antibiotics harmless to bacteria (Julien Delmas, et al., 2010).
Consequently, the CTXM-family calls for attention for the
design of inhibitors.
Table 4 Induced fit docking results of compounds T3, T5 and cefotaxime
at the substrate binding site
Hydrogen bond
Glide Glide energy,
Triazolophanes score kcal molÀ1
D–HÁ Á ÁA
Distance (Å)
Table 3 Glide score and glide energy of compounds T2, T3, T4 and T5
T3
À5.27 À46.05
Ans104 N–HÁ Á ÁO 3.26
Ans132 N–HÁ Á ÁO 3.06
Ans132 N–HÁ Á ÁO 3.01
Thr235 O–HÁ Á ÁO 3.01
Asn132 N–HÁ Á ÁO 3.01
Asn104 N–HÁ Á ÁO 3.00
Triazolophanes
Glide score
Glide energy, kcal molÀ1
T4
T5
T2
T3
À3.52
À3.41
À2.55
À3.42
À31.92
À34.67
À40.70
À34.80
T5
À4.74 À52.30
À8.07 À69.33
Cefotaxime
(co-crystal)
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dendrimers are already reported to possess a variety of biolo-
gical functions and an attempt to evaluate their larvicidal
activity was carried out.
The larvicidal activity was determined according to the WHO
(World Health Organization) protocol26 with slight modifica-
tion. The test compounds were dissolved in 10 mL of DMSO due
to its solubility in water. The mosquito larvae were treated with
the compounds at a concentration of 2000 mg mLÀ1. The larvae
treated with DMSO were maintained as a control. The mortality
of fourth instar larvae of Aedes aegypti was observed and the
number of surviving larvae at the end of 24 and 48 hours was
observed. The percentage of mortality was calculated using the
below formula:
Percentage of mortality = (No. of larva dead/
No. of larvae introduced) Â 100
The larvae treated with the test compounds showed signifi-
cant behavioral changes which include restlessness, loss of
equilibrium and finally death. The percentage of mortality
Fig. 4 Molecular docking of compound T3 in the active pocket of protein varies among the compounds tested. The high mortality per-
CTXM (PDBID-3HLW).
centage of 90% was observed in larvae treated with triazolo-
phane T5 followed by compounds T3 and T4 with 80%
mortality each. Among the synthesized triazolophanes T6, T7,
affinity to the target proteins. The electron donating triazole and
T8, T9 and T10 show low mortality percentage. Triazolophanes
oxygen present in the structure could interact by hydrogen bond-
T1, T2 and T3 show moderate mortality percentage when
ing on the macrocycles and enhanced the antibacterial activity.
compared with the other triazolophanes. The results are tabulated
Among the 1 : 1 and 2 : 2 oligomeric triazolophanes the inhibition
in Table 5.
activity depends on the nature of the substituents. Triazolophane
In conclusion, ester based 1 : 1 and 2 : 2 oligomeric triazolo-
T6 showed moderate activity because of the azobenzene along with
phanes 1–10 have been successfully achieved under mild con-
a triazole unit in the macrocycles. The triazolophane T7 showed
ditions. Nitroarene substituted triazolophanes 1 and 6 showed
better activity than all other triazolophanes due to the electron
a strong absorption band between 397 and 399 nm assigned
withdrawing groups, such as nitro and ester groups, present in the
to n–p* transitions of the azobenzene chromophore. In vitro
p-position of the intra annular position. The 1 : 1 oligomers (1–5)
antibacterial studies and molecular docking analysis of the
showed better antibacterial activity than the 2 : 2 oligomers (6–10)
compounds against four human pathogens Staphylococcus
because of their high solubility in polar solvents, and hence they
aureus (MTCC96), Bacillus subtilis (MTCC441), Salmonella typhi
can be easily applied to a substrate, and they also have aliphatic
(ATCC 6539) and Escherichia coli (MTCC 1698) revealed that
chain. Thus, the nature of the aromatic unit with an ester and
triazolophanes T3 and T5 exhibited better antibacterial activity
triazole skeleton attached to phenoxy molecules has a strong
than the other triazolophanes. All the 1 : 1 oligomeric triazolo-
influence on the extent of antibacterial activity.
phanes show better antibacterial activity against Staphylococcus
aureus (MTCC96), Bacillus subtilis (MTCC441), Salmonella typhi
Larvicidal activity
Mosquitoes act as a vector for many subtropical and tropical
diseases which are very harmful to humans. The mosquito
Table 5 Larvicidal activity of the synthesized triazolophanes 1–10 at
spreads diseases such as chikunguniya, dengue fever, dengue 2000 mg mLÀ1 by larvicidal activity assay
hemorrhagic fever and yellow fever. Among these common
Mortality
diseases, dengue hemorrhagic fever is highly fatal and it is
Larvae
Triazolophanes
percentage (%)
transmitted through the vector Aedes aegypti. The WHO esti-
mates that there may be nearly 50 million people affected by
dengue fever worldwide every year. The vaccine for this virus is
still at an early stage and therefore the only available method
to reduce the disease infection is by controlling the vector.
The vectors can be controlled either by killing, preventing the
mosquitoes from biting humans and causing mortality to
the mosquito larvae on a large scale. New approaches are
needed for the control of these vectors. The cyclophanes and
4th instar larvae Aedes aegypti
T1
T2
T3
T4
T5
T6
T7
T8
50
70
80
80
90
60
30
30
40
30
0
T9
T10
Control (DMSO)
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Conflicts of interest
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There are no conflicts to declare.
Acknowledgements
The authors acknowledge UGC, New Delhi, India for financial
support and DST, New Delhi for the NMR facility under the
DST-FIST programme to the Department of Organic Chemistry,
University of Madras. SS thanks DST PURSE Phase II for
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