Synthesis of selenolo(2,3-b)quinoline-2-carboxylic ethyl esters: Cytogenetic studies on human peripheral blood leucocyte cultures, and anti-bacterial studies, and anti-fungal studies of their effects

Article abstract of DOI:10.1080/104265090889512

The compounds selenolo(2,3-b)quinoline-2-carboxylic ethyl esters were synthesized in good yields by the reaction of 3-(2-chloro-3-quinolyl)acrylic ethyl esters, with the nucleophilic reagent sodium diselenide in ethanol medium under a nitrogen atmosphere. Cytogenetic studies on human blood leucocytes in vitro were evaluated for some of the synthesized compounds. Most of the synthesized compounds were tested for their antibacterial and antifungal activities. Copyright Taylor & Francis Inc.

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Synthesis of Selenolo(2,3-
b)quinoline-2-carboxylic Ethyl
Esters: Cytogenetic Studies
on Human Peripheral Blood
Leucocyte Cultures, and Anti-
Bacterial Studies, and Anti-
Fungal Studies of Their Effects
V. Nithyadevi a & S. P. Rajendran a
a Department of Chemistry, Bharathiar University ,
Coimbatore, Tamil Nadu, India
Published online: 18 Aug 2006.
To cite this article: V. Nithyadevi & S. P. Rajendran (2005) Synthesis of Selenolo(2,3-
b)quinoline-2-carboxylic Ethyl Esters: Cytogenetic Studies on Human Peripheral Blood
Leucocyte Cultures, and Anti-Bacterial Studies, and Anti-Fungal Studies of Their
Effects, Phosphorus, Sulfur, and Silicon and the Related Elements, 180:8, 1849-1862,
DOI: 10.1080/104265090889512
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Phosphorus, Sulfur, and Silicon, 180:1849–1862, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090889512
Synthesis of Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Esters: Cytogenetic Studies on Human Peripheral Blood
Leucocyte Cultures, and Anti-Bacterial Studies, and
Anti-Fungal Studies of Their Effects
V. Nithyadevi
S. P. Rajendran
Department of Chemistry, Bharathiar University, Coimbatore,
Tamil Nadu, India
The compounds selenolo(2,3-b)quinoline-2-carboxylic ethyl esters were synthesized
in good yields by the reaction of 3-(2-chloro-3-quinolyl)acrylic ethyl esters, with
the nucleophilic reagent sodium diselenide in ethanol medium under a nitrogen
atmosphere. Cytogenetic studies on human blood leucocytes in vitro were evaluated
for some of the synthesized compounds. Most of the synthesized compounds were
tested for their antibacterial and antifungal activities.
Keywords Condensation; cyclisation using sodium diselenide; dehydroxychlorination;
esterification; hydrolysis; Vilsmeier-Haack Reaction
INTRODUCTION
(i). Selenium
It is known to be an important dietary antioxidant and essential
component of the active sites of a number of enzymes and several
Received June 16, 2004; accepted September 7, 2004.
We wish to thank Bharathiar University for the award of URF to V.N. We also thank
the services rendered by the Department of Chemistry, Bharathiar University Coimbat-
ore, IICT Hyderabad, and the Sophisticated Instrumentation Facility at IISc, Bangalore,
for recording Proton NMR, IR, and Mass spectra. We convey our thanks to Dr. M. Balaji,
Department of Medical Genetics, K. G. Hospital, Coimbatore, for carrying out the cytoge-
netic studies. We greatly acknowledge Dr. P. Lakshmana Perumalsamy and Mr. Subash
kumar—Division of microbiology, Department of Environmental Sciences, Bharathiar
University, Coimbatore, for the microbial studies rendered by them.
Presented as a poster presentation entitled “Synthesis of Selenolo(2,3-b)quinoline-2-
carboxylic Ethyl Esters and Their Cytogenetic Studies on Human Chromosomes, Antibac-
terial Studies, Antifungal Studies” in the IXth International Conference on the Chemistry
of Selenium and Tellurium held on 23–27th of February 2004.
Address correspondence to S. P. Rajendran, Department of Chemistry, Bharathiar
University, Coimbatore 641046, Tamil Nadu, India. E-mail: rajendransp@yahoo.com
1849

1850
V. Nithyadevi and S. P. Rajendran
additional mammalian selenoproteins. Dietary selenium deficiency has
been linked to diseases as diverse as cancer,1 heart disease,2 arthritis,3
and AIDS.4 Organoselenium compounds have been extensively inves-
tigated due to their close association with various type of activities
such as antifungal and antibacterial activities;5−7 cardiovascular and
antihistaminic actions;8 antiadrenalin, antiradiation,9 antileukemic
activity;10 antitumour activity,11 analgesic, antirheumatic, and an-
tipyretic activities;12 and parathyroid scanning for the deduction of
lymphomas,13 etc.
Early workers from our laboratory have synthesized selenolo(2,3-
b)quinolines14−16 using 2-quinolone-3-ethanols and 2-chloro-3-vinyl
quinolines as the starting compounds. In view of their remarkable ac-
tivities, we pursued our investigation on selenium heterocycles and
we report herein an expedient and convenient procedure for the
synthesis of selenolo(2,3-b)quinoline-2-carboxylic ethyl esters (6) in
very good yields from 3-(2-chloro-3-quinolyl)acrylic ethyl esters (5)
(Scheme 1).
SCHEME 1 (i) 4M HCl (ii) Malonic acid, pyridine, piperidine, (iii) abs. ethanol,
conc. H2SO4 (iv) POCl3 (v) Na2Se2. (a) R1 R2 R3 H, (b) R1 CH3, R2 R3 H,
(c) R1 R3 H, R2 CH3, (d) R1 R2 H, R3 CH3, (e) R1 OCH3, R2 R3 H,
(f) R1 R3 H, R2 OCH3.
(ii). Cytogenetic Studies
DNA molecular assay is extensively used in in-vitro and in-vivo genetic
drug toxicology. Different types of cell lines and practically any type of
cell from any target organs can be tested on molecular assay.

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1851
DNA molecular assay can be used to study the damage in cells in
different cell cycle phases. The rationale of this application is propor-
tional to the DNA content in cells. Alternatively, it is possible to use
this approach for an unknown cell line on the basis of distribution, the
comet fluorescence as measured by the DNA molecular assay.
Chemicals or drugs capable of interacting with DNA have a high
probability of being carcinogenic or otherwise hazardous. Genetic ef-
fects of various diseases and drugs can be detected by their interactions
with DNA and by the consequences of these interactions such as chro-
mosome alterations, mutagenesis, and the inhibition of DNA synthesis
and DNA repair. The carcinogenesis or mutagens of drugs involve an
alteration in DNA that must be stable and permanent so that it can be
transmitted in subsequent genetic copies.
The SCG/Comet analysis is becoming more significant because of its
simplicity, speed, and requirement of only a few cells. Blood cells embed-
ded in low-melting agrarose, when treated with high-salt lysis solution,
retain only high mol.-wt. supercoiled DNA. When placed in an alkaline
solution, it commences to unwind from sites of strand breakage. When
an electric current is then applied, DNA fragments stream towards the
anode giving the appearance of a ‘Comet tail.’ Undamaged DNA re-
mains trapped within the nucleolus. The length of these comet tails is
indicative of the extent of DNA damage. DNA damage is likely to hap-
pen under oxidative stress. Direct binding of drug compounds could be
the possible reason for the DNA single damage.
EXPERIMENTAL
Melting points were determined using Raaga melting point apparatus
and were uncorrected. The IR spectra were recorded on an FTIR 8201
(PC)S spectrometer as KBr pellets and the absorption frequencies are
expressed in reciprocal centimeters (cm−1). Proton NMR spectra were
recorded on a Gemini-200 MHz or on a Varian AMX 400 spectrometer
in CDCl3. The chemical shifts were expressed in δ (ppm) downfield from
tetramethylsilane as an internal standard. Elemental analysis was per-
formed by a Perkin-Elmer model 240B CHN analyzer and the values are
within the permissible limits ( 0.5). The mass spectra were recorded
by an EIMS technique on an Autospec mass spectrometer. The crude
products were checked by thin-layer chromatography and purified by
column chromatography using silica gel (60–120 mesh).
(i). In our present work selenium heterocycles were synthesized from
the potential precursor 2-chloro-3-formyl quinolines, which were pre-
pared by following the O. Meth-cohn procedure.17 2-chloro-3-formyl
quinolines (1) were converted to the oxo compounds (2) by refluxing

1852
V. Nithyadevi and S. P. Rajendran
with 4 MHCl. These were then condensed with malonic acid under the
conditions of the Knoevenagel reaction to furnish 3-(2-oxo-1, 2-dihydro-
3-quinolyl)acrylic acids18 (3).
Esterification of 3-(2-Oxo-1,2-dihydro-3-quinolyl)acrylic
Acid (4)
The ethyl ester was obtained in an almost quantitative yield by boiling
the acrylic acid (3) (3 g) with concentrated sulphuric acid (4.5 mL) and
absolute ethanol (150 mL). The acid gradually passed into the solution
after boiling for 5–6 h on a steam bath. The solution was then allowed
to cool, and a mass of needles of ester formed. A considerable quantity
was further precipitated by dilution with two volumes of water. The
whole solid was collected, washed with water, dried, recrystallised from
ethanol, and was ready for further use.
Preparation of 3-(2-Chloro-3-quinolyl)acrylic Ethyl Ester (5)
The ester (4) (0. 0228 mole) was treated with freshly distilled phospho-
rus oxychloride (13.6 mL, 0. 148 mole) and kept on a steam bath for
5–6 hrs. On cooling and pouring into crushed ice, the compound sepa-
rated as a creamy white solid. It was then recrystallised from petroleum
ether:benzene (4:1 v/v) and obtained as colourless needles (Table I).
Preparation of Selenolo(2,3-b)quinoline-2-carboxylic
Ethyl Ester (6)
To a freshly prepared solution of sodium diselenide19 [selenium powder
(0. 0120 mole, 0.955 g) and sodium borohydride (0. 00846 mole, 0.319 g)
in ethanol], chloroester (5) (1 g, 0.00404 mole) was added and heated
under reflux temperature for 15–16 h on a steam bath. Thereafter the
TABLE I Physical and IR Data of 5a–f∗
Compound Yield %
M.p◦C
IR(cm−1
)
Mass m/e
5a
5b
5c
5d
5e
5f
85
87
89
92
80
85
120–122 1710, 1267, 1064
90–92 1701, 1263, 1041
135–137 1708, 1265, 1039
144–146 1711, 1274, 1031
261, 263
275, 277
275, 277
275, 277
291, 293
291, 293
96–98
1709, 1269, 1049
115–117 1712, 1261, 1026
∗Recrystallised from petroleum ether:benzene (4:1 v/v).

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1853
solution was evaporated and the residue was dissolved in chloroform
followed by washing with water. The organic extract was dried and
evaporated. The residue was then chromatographed over silicagel with
pet. ether (60–80◦C) as the eluent.
PHYSICAL AND SPECTROSCOPIC DATA OF (6A–F)
Selenolo(2,3-b)-quinoline-2-carboxylic Ethyl Ester (6a)
Light yellow needle-shaped crystals, Yield = 65%, Melting point = 194–
196◦C, (Cal: C, 55.20; H, 3.64; N, 4.62; Found: C, 55.4; H, 3.50; N, 4.59),
IR (KBr, cm−1) = 1726 ( C O of ester), 1192 ( C O of ester), 1H NMR
(CDCl3) δppm: 1.40 (t, J = 7 Hz, CH3 of ester), 4.30 (q, J = 7 Hz,
OCH2 of ester), 7.28–8.01 (m, 6H, C3, C4, C5, C6, C7, C8 H), M.F. =
C14H11 NO2Se, Mass (m/z)M+ = 304.
6-Methyl Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Ester (6b)
Light yellow needle shaped crystals, Yield = 60%, Melting point = 159–
161◦C, (Cal: C, 56.59; H, 4.12; N, 4.42; Found: C, 56.50; H, 4.10; N,
4.40), IR (KBr, cm−1) = 1709 (C O of ester), 1251 ( C O of ester), 1H
NMR (CDCl3) δppm: 1.43 (t, J = 7 Hz, CH3 of ester), 4.42 (q, J = 7 Hz,
OCH2 of ester), 2.57 (s, 3H, CH3), 8.26 (s, 1H, C4 H), 8.53 (s, C3 H),
8.13 (d, J = 2 Hz, C5 H), 8.03 (s, C7 H),7.64 (d, C8 H, J = 8.2 Hz).
M.F. = C15H13NO2Se, Mass (m/z)M+ = 318.
7-Methyl Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Ester (6c)
Light yellow needle-shaped crystals, Yield = 66%, Melting point = 178–
180◦C, (Cal: C, 56.59; H, 4.12; N, 4.42; Found: C, 56.60; H, 4.12; N,
4.50), IR (KBr, cm−1) = 1712 (C O of ester), 1251 ( C O of ester), 1H
NMR (CDCl3) δppm: 1.42 (t, J = 6.6 Hz, CH3 of ester), 4.44 (q, J =
6.8 Hz OCH2 of ester), 2.61 (s, 3H, CH3), 8.25 (s, 1H, C4 H), 8.56
(s, C3 H) 7.39–7.92 (m, 3H, C5, C6, C8 H). M.F. = C15H13NO2Se, Mass
(m/z)M+ = 318.
8-Methyl Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Ester (6d)
Light yellow needle-shaped crystals, Yield = 75%, Melting point = 164–
166◦C, (Cal: C, 56.59; H, 4.12; N, 4.42; Found: C, 56.60; H, 4.12; N,

1854
V. Nithyadevi and S. P. Rajendran
4.50), IR (KBr, cm−1) = 1724 (C O of ester), 1254 ( C O of ester), 1H
NMR (CDCl3) δppm: 8.25 (s, C4 H), 8.56 (s, C3 H), 7.45 (t, J = 7.4 Hz,
C6 H), 7.79 (d, J = 8 Hz, C5 H), 7.63 (d, J = 7 Hz, C7 H), 2.86 (s,
3H, CH3), 1.44 (t, J = 7 Hz, 3H, CH3 (of ester)), 4.43 (q, J = 7 Hz, 2H,
OCH2). M.E. = C15 H 13NO2Se, Mass (m/z)M+ = 318.
6-Methoxy Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Ester (6e)
Light yellow needle-shaped crystals, Yield = 66%, Melting point = 145–
147◦C, (Cal: C, 53.88; H, 3.92; N, 4.21; Found: C, 53.80; H, 3.99; N,
4.21), IR (KBr, cm−1) = 1718 (C O of ester), 1242 ( C O of ester),
1H NMR (CDCl3) δppm: 8.28 (s, C4 H), 8.54 (s, C3 H), 7.51–7.93 (m,
3H, C5, C7, C8 H), 4.47 (q, J = 7.6 Hz, 2H, OCH2), 3.99 (s, 3H, OCH3)
1.46 (t, J = 6.4 Hz, 3H, CH3) M.F. = C15 H13 NO3Se, Mass (m/z)M+ =
334.
7-Methoxy Selenolo(2,3-b)quinoline-2-carboxylic Ethyl
Ester (6f)
Light yellow needle-shaped crystals, Yield = 58%, Melting point = 154–
156◦C, (Cal: C, 53.88; H, 3.92; N, 4.21; Found: C, 53.89; H, 3.99; N,
4.15), IR (KBr, cm−1) = 1700 (C O of ester), 1245 ( C O of ester), 1H
NMR (CDCl3) δppm: 8.23 (s, C4 H), 8.50 (s, C3 H), 7.24–7.84 (m, 3H,
C5, C6, C8 H), 3.97 (s, 3H, OCH3), 1.45 (t, 3H, CH3), 4.40 (q, J =
6.2 Hz, OCH 2) M.F. = C15H13NO3Se, Mass (m/z)M+ = 334.
(ii). Cytogenetic Studies
DNA molecular assay was carried out for some of the synthesized
compounds 7-methoxy-selenolo(2,3-b)quinoline-2-carboxylic ethyl ester
(6f), 8-methyl-selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6d),
and 6-methyl-selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6b).
Cell Culture from Peripheral Blood Leucocytes
Cultures of leucocytes obtained from peripheral blood were set up
following the method of Hungerford.20 The chromosomal preparation
obtained were strained with Giemsa and were also processed to obtain
G-bands.
Leucocyte Cultures In-Vitro
The experiments were carried out as outlined by Hungerford.20 Three
experiments were carried out using three nonsmoking healthy male

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1855
donors, ages 23, 24, and 25 years. Intravenous blood was collected
aseptically and whole blood was cultured with McCoy’s medium con-
taining 25% human AB serum, 0.5% phytohemagglutinin, and 0.25%
Dicrystin-S. The test compounds were dissolved in 1% CHCl3. Four dif-
ferent concentrations of 0.02, 0.2, 2, and 20 µg/mL were added to the
culture medium (0.1 mL solution of the compounds (6f), (6d), and (6b)
8 mL of the medium) at 0, 24, and 48 h after culture initiation, indicated
as treatment for 72, 48, and 24 hr, respectively. Triplicate cultures for
each dose from three donors were maintained for the study of chromoso-
mal aberrations. Control-I was given an equal volume of distilled water.
Control-II was given an equal volume of 1% CHCl3. 0.1 mL CHCl3 was
added to 8 mL of medium at 0, 24, and 48 h after culture initiation
indicated as treatment for 72, 48, and 24 h respectively. All cultures
were incubated at 37◦C for the 72-h slides, which were prepared using
the method of Moorhead et al.21
Analysis of Chromosomal Aberrations
All the prepared slides were strained with Giemsa. Three hun-
dred and fifty well-spread metaphase plates were screened for
chromosome aberrations. The aberrations include chromatid gaps, chro-
matid breaks, isochromatic breaks, and chromatid interchanges. Poly-
ploid cells were also screened in all the slides.
Preparation of Slides
A test slide was prepared by placing a drop of the cells suspended on a
clean, chilled slide, immediately drying it on a slide by keeping the slide
at 40◦C for few seconds. Thereafter, the dried slides were strained with
giemsa for 10 min and air dried. Three hundred and fifty well-banded
metaphases were analysed under an oil-immersion lens by Olympus
microscope.
The clastogenic properties of the compounds (6f), (6d), and (6b) were
studied by investigating the effects of the compounds on human chro-
mosomes in-vitro in leukocyte cultures.
(iii). Antibacterial Activity
Methodology
Antibacterial activity of selenolo(2,3-b)quinoline-2-carboxylic ethyl
ester (6a) and its derivatives: 7-CH3 (6c), 6-CH3 (6b), 7-Ome (6f), and
8-CH3 (6d) were screened for the in-vitro growth inhibitory activity
against Escherichia coli, Aeromonas hydrophila, Salmonella typhi, and
Pseudomonas aeurginosa.

1856
V. Nithyadevi and S. P. Rajendran
Anti-bacterial activity of the synthesized compounds were deter-
mined by Disc diffusion technique.22 About 105 concentration of bac-
terial cells were enriched in 5 mL of the nutrient broth (NaCl-5.0 g,
peptone-5 g, beef extract-3 g, yeast extract-3 g in 1000 mL of distilled
water, pH = 7.3 0.2).
Enriched bacterial cells were swabbed onto a Muller Hinton Agar
medium (Himedia India). The test compounds were dissolved in CHCl3
to a final concentration of 0.25%, 0.5%, and 1% and soaked in filter paper
discs of (5 mm diameters and 1 mm thickness). These discs were placed
on the seeded plates and incubated at 37◦C for 24 h. The zones of inhibi-
tion around the discs were measured after 24 h. Norfloxacin(Nx)-10 mcg
and Amoxycillin(Ac)-30 mcg were used as the standard to compare the
antibacterial activity of the compounds.
(iv). Antifungal Activity
Antifungal activity of selenolo(2,3-b)quinoline-2-carboxylic ethyl ester
(6a) and its derivatives: 7-CH3 (6c), 6-CH3 (6b), 7-Ome (6f), and 8-CH3
(6d) were screened for in-vitro growth inhibitory activity against As-
pergillus niger, Aspergillus flavus, and Fusarium spp using the disc dif-
fusion method.5 The above fungal spores were enriched in sabouraud
dextrose broath (dextrose-10 g, peptone-10 g, chloramphenicol-0.002 g,
distilled water-1000 mL, pH-5.6
0.2) and incubated at room tem-
perature for 4–6 days. The enriched fungal mycelium were cultured
in a sabouraud dextrose agar medium (dextrose-10 g, peptone-10 g,
chloramphenicol-0.002 g, distilled water-1000 mL, pH-5.6 0.2, agar-
20 g. The test compounds were dissolved in CHCl3 to a final concentra-
tion of 0.25%, 0.5%, and 1% and soaked in filter-paper discs. These discs
were placed on the seeded plates and incubated at room temperature
for 4–6 days. After 4 days the inhibition zones appearing around the
discs in each plate were measured and tabulated using Carbendazim
and Fluconazole (Himedia, India) and were used as the standard.
RESULTS AND DISCUSSION
(i). Even though there are many inorganic selenium reagents and
organoselenium reagents, the role of Na2Se2 is excellent when it is used
for the introduction of selenium into organic molecules. The ethanolic
solution of sodium diselenide is advantageous, as it provides a supe-
rior solvent for nucleophilic displacement reactions in water insoluble
or hydrolysis-sensitive organic compounds. In this context it is rele-
vant to mention the synthesis of selenolo(2,3-b)quinolines by reacting 2-
chloro-3-vinyl quinolines with Na2Se2 prepared in situ by Shanmugam

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1857
et al.15 The present work was started with the synthesis of 8-methyl
derivatives.
The compound (5d) was synthesized by dehydroxychlorination of
8-methyl-3-(2-oxo-1,2-dihydro-3-quinolyl)acrylic acid (4d) with freshly
distilled phosphorus oxychloride on a steam bath for 5–6 h. This was
followed by recrystallisation from pet. ether: benzene (4:1 v/v), giving
rise to colorless needle-shaped crystals melting at 144◦C. The structure
of (5d) was attested through the following spectral values.
IR(KBr)Cm−1: 1711 ( C O of ester), 1031 ( C Cl), 1H-NMR
(CDCl3) δ(ppm):8.33 (s, C4 H), 8.15, 6.56 (d, 1H each CH CHtrans
,
J = 16 Hz), 7.69 (d, J = 8 Hz, C7 H), 7.60 (d, J = 7.4 Hz, C5 H), 7.47
(t, J = 7.4 Hz, C6 H), 1.49 (t, J = 7 Hz, 3H, CH3 (of ester)), 4.44 (q,
J = 7 Hz, 2H, OCH2), Mass spectra: m/e = 275(M+), 277 (M+2) which
is one third the intensity of the parent peak, attested to the structure
of the compound as 8-methyl-3-(2-chloro-3-quinolyl)acrylic ethyl ester
(5d).
The compound (5d) formed a very good intermediate for the syn-
thesis of the selenium heterocycles in good yields by reacting it with
a freshly prepared solution of sodium diselenide in absolute ethanol
on a steam bath. The starting compound (5d) completely disappeared
during a course of 15 h as revealed by the TLC analysis. Thereafter
the solution was evaporated and the residue obtained was taken up
with chloroform and washed with water. The chloroform extract was
dried and evaporated. The obtained residue was purified through col-
umn chromatography using petroleum ether as the eluent. The product
was obtained as light yellow needle-shaped crystals upon recrystallisa-
tion from petroleum ether with m.p 164–166◦C in 75% yield.
Strong peaks at 1724 cm−1 ( C O of ester) and 1254 cm−1 ( C O
of ester) in IR spectrum, three singlets at δ 8.25, δ 8.56, and δ 2.86, two
triplets at δ 7.45 and δ 1.44, two doublets at δ 7.79, δ 7.63, one quartet
1
at δ 4.43 in H NMR spectrum, molecular ion peak at 318(M+) with
characteristic isotopic abundance pattern expected for selenium con-
taining compounds in mass spectrum, clearly indicated the structure
as 8-methyl selenolo(2,-3-b)quinoline-2-carboxylic ethyl ester (6d).
The above reaction sequences were extended to synthesize 6a, 6b,
6c, 6e, and 6f derivatives, respectively.
(ii). Cytogenetic Studies
The data of the compounds (6b), (6d), and (6f) were pooled. It was noted
from Table II that the compound showed chromosomal aberrations as
a dose dependant increase. An increase was seen only with the concen-
tration of 20 µg/mL, when the compound (6f) was added at 24 h, 48 h

1858
V. Nithyadevi and S. P. Rajendran
TABLE II Number of Chromosomal Aberrations In Vitro Following
Addition of the Compound (6f) at 0, 24, and 48 h After Culture
Initiation
Concentration
of the
Average
no of
Gaps
Breaks
compound
metaphases/r
Isochro
Isochro Chromatid
(6f) (µg/mL) eplicate (n = 3) Chromatid matid Chromatid matid interchange Total
0 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
24 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
20
10(2.85)
8(2.28)
18 1.00
48 h
Control—I
Control—II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
20
5(1.42)
5(1.42)
10 0.00
Mean values are the number of aberrations from three replicate donors (on average
350 cells) values in parentheses are percentages.
Control-I was given an equal volume of distilled water.
Control-II was given an equal volume of 1% CHCl3.
after culture initiation. Chromosomal aberrations like chromatid gaps
and chromatid breaks were observed. Polypolid cells were absent in all
the examined slides. However, it was inferred from Tables III and IV
that compounds (6d) and (6b) caused no chromosomal aberrations at
all concentrations.
In the present study, it was inferred that the compound (6f) was a
very mild mutagen and at higher concentration it might cause geno-
toxicity in humans. However, compounds (6d) and (6b) did not cause
genotoxicity in humans.
(iii). Anti-Bacterial Activity
6-CH3 selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6b) was sen-
sitive against E. coli and A. hydrophila at 1% CHCl3, S. typhi at

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1859
TABLE III Number of Chromosomal Aberrations In Vitro Following
Addition of the Compound (6d) at 0, 24, and 48 h After Culture
Initiation
Concentration
of the
Average
no of
Gaps
Breaks
compound
metaphases/r
Isochro
Isochro Chromatid
(6d) (µg/mL) eplicate (n = 3) Chromatid matid Chromatid matid interchange Total
0 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
24 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
48 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
Mean values are the number of aberrations from three replicate donors (on average
350 cells) values in parentheses are percentages.
Control-I was given an equal volume of distilled water.
Control-II was given an equal volume of 1% CHCl3.
0.25% CHCl3. Intermediate against Ps. aeurginosa at 0.25% CHCl3.
The pathogens E. coli, S. typhi, Ps. aeurginosa and A. hydrophila were
resistant at 0.5% chloroform.
7-OCH3 selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6f) was in-
termediate against all the test organisms and resistant against A. hy-
drophila at all concentrations. With an increase in concentration the
test compound (6f) was resistant against all the pathogens at all concen-
trations. 8-CH3 selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6d)
was sensitive against S. typhi at 0.5% CHCl3, intermediate against
E. coli and Ps. aeurginosa, and resistant against. A. hydrophila at all
concentrations. Selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6a)
was resistant against all the pathogens at all concentrations. 7-CH3
selenolo(2,3-b)quinoline-2-carboxylic ethyl ester (6c) was intermediate

1860
V. Nithyadevi and S. P. Rajendran
TABLE IV Number of Chromosomal Aberrations In Vitro Following
Addition of the Compound (6b) at 0, 24, and 48 h After Culture
Initiation
Concentration
of the
Average
no of
Gaps
Breaks
compound
metaphases/r
Isochro
Isochro Chromatid
(6b) (µg/mL) eplicate (n = 3) Chromatid matid Chromatid matid interchange Total
0 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
24 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
48 h
Control-I
Control-II
0.02
0.2
2
350/3
350/3
350/3
350/3
350/3
350/3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0.0
0.0
0.0
0.0
0.0
0.0
20
Mean values are the number of aberrations from three replicate donors (on average
350 cells) values in parentheses are percentages.
Control-I was given an equal volume of distilled water.
Control-II was given an equal volume of 1% CHCl3.
TABLE V Antibacterial Activity
Diameter of inhibition zone in mm
Escherichia
coli
Aeromonas
hydrophila
Salmonella
typhi
Pseudomonas
aeurginosa
Compounds 0.25% 0.5% 1% 0.25% 0.5% 1% 0.25% 0.5% 1% 0.25% 0.5% 1%
6a
6c
6b
6f
6d
Nx
Ac
12
14
15
17
12
28
21
0
0
0
0
11
16
15
0
12
21
28
0
12
12 18
0
0
0
0
13
0
0
0
0
0
13
17
16
16
16
24
—
0
0
12 11
12 11
12 11
12 11
24 24
12 19
12 11
14 17
28 28
21 21
18
17
14
24
24
12 12
12 12
19 11
24 24
24 24
0
0
21 21
28 28
—
—

Selenolo Quinoline-2-Carboxylic Ethyl Esters
1861
TABLE VI Antifungal Activity
Diameter of inhibition zone in mm
Aspergillus niger Aspergillus flavus Fusarium spp
Compounds 0.25% 0.5% 1% 0.25% 0.5% 1% 0.25% 0.5% 1%
6a
6c
6b
6f
—
11
12
11
16
—
15
13
11
15
—
14
12
10
15
11
14
17
—
11
13
14
12
—
16
12
13
12
—
15
11
—
—
—
—
11
—
—
—
—
10
—
—
—
—
6d
against A. hydrophila and Ps. aeurginosa at 0.5% CHCl3 and resistant
against E. coli and S. typhi.
Generally 6-CH3 derivative was more sensitive to the test organisms
than the other derivatives. The overall results showed that the deriva-
tives could not reach the effectiveness of the conventional bactericide,
Norfloxacin and Amoxycillin (Table V).
(iv). Antifungal Activity
All the test compounds were resistant to fusarium spp at all concentra-
tions. (6b) and (6d) showed intermediate activity against Aspergillus
flavus at 0.25% and 0.5% CHCl3, but was resistant at other concentra-
tion. (6a), (6c), (6b), and (6f) were resistant to Aspergillus niger but
(6d) showed intermediate activity at 0.25% CHCl3. The results gave a
clear picture with regard to the inhibition zone, which decreased with
an increase in concentration of the test solution containing the above
compounds. The overall results showed that the derivatives could not
reach the effectiveness of the conventional fungicide, Carbendazim and
Fluconazole (Himedia, India) (Table VI).
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