Synthesis, spectral analysis and in vitro cytotoxicity of diorganotin (IV) complexes derived from indole-3-butyric hydrazide

Article abstract of DOI:10.1002/aoc.5815

A series (1–20) of diorganotin (IV) complexes with general formula R₂SnL were formed by the reaction of R₂SnCl₂ (where R = Me, Et, Bu and Ph) with Schiff base ligands (H₂L^1–4) derived from the reaction of indole-3-butyric hydrazide with the salicylaldehyde and its derivatives. The structure elucidation of compounds were done by using UV–Vis, FT-IR, NMR (¹H, ¹³C, ¹¹⁹Sn), Mass spectrometry and thermal gravimetric analysis. Spectroscopic evidences suggested tridentate nature (ONO) of Schiff base ligands and coordinated to the dialkyl/diaryltin (IV) moieties through nitrogen and oxygen donor sites giving pentacoordinated geometry to complexes. The compounds were tested for the antimicrobial activity against bacterial and fungal strains which showed promising biological activity with compound 20 (Ph₂SnL⁴) as most active against microbes. The in silico study of the compounds was carried and observed that the compounds are used as orally active drugs and promote the formation of different hydrazide based drugs. The synthesized compounds were tested against human carcinoma cell lines namely A549, MCF7 and one normal cell line IMR 90 using MTT assay. The diethyl and dibutyltin complexes of Schiff bases displayed good cytotoxic activities. Compound 3 (H₂L³) and 10 (Et₂SnL²) were most potent against cancer cell lines with lowest IC₅₀ values and 7–8 times less toxic against the normal cell line.

Full text of DOI:10.1002/aoc.5815

Received: 9 January 2020
DOI: 10.1002/aoc.5815
Revised: 20 April 2020
Accepted: 27 April 2020
F U L L P A P E R
Synthesis, spectral analysis and in vitro cytotoxicity of
diorganotin (IV) complexes derived from indole-3-butyric
hydrazide
Jai Devi1
| Jyoti Yadav1 | Deepak Kumar2 | Deepak Kumar Jindal3
|
Biswarup Basu4
1Department of Chemistry, Guru
Jambheshwar University of Science and
Technology, Hisar, Haryana, 125001,
India
A series (1–20) of diorganotin (IV) complexes with general formula R2SnL
were formed by the reaction of R2SnCl2 (where R = Me, Et, Bu and Ph) with
Schiff base ligands (H2L1–4) derived from the reaction of indole-3-butyric
hydrazide with the salicylaldehyde and its derivatives. The structure elucida-
tion of compounds were done by using UV–Vis, FT-IR, NMR (1H, 13C, 119Sn),
Mass spectrometry and thermal gravimetric analysis. Spectroscopic evidences
suggested tridentate nature (ONO) of Schiff base ligands and coordinated to
the dialkyl/diaryltin (IV) moieties through nitrogen and oxygen donor sites
giving pentacoordinated geometry to complexes. The compounds were tested
for the antimicrobial activity against bacterial and fungal strains which showed
promising biological activity with compound 20 (Ph2SnL4) as most active
against microbes. The in silico study of the compounds was carried and
observed that the compounds are used as orally active drugs and promote the
formation of different hydrazide based drugs. The synthesized compounds
were tested against human carcinoma cell lines namely A549, MCF7 and one
normal cell line IMR 90 using MTT assay. The diethyl and dibutyltin com-
plexes of Schiff bases displayed good cytotoxic activities. Compound 3 (H2L3)
and 10 (Et2SnL2) were most potent against cancer cell lines with lowest IC50
values and 7–8 times less toxic against the normal cell line.
2School of Pharmaceutical Sciences,
Shoolini University, Solan, 173212, India
3Department of Pharmaceutical Sciences,
Guru Jambheshwar University of Science
and Technology, Hisar, Haryana, 125001,
India
4Department of Neuroendocrinology &
Experimental Hematology, Chittaranjan
National Cancer Institute, Kolkata,
700026, India
Correspondence
Jai Devi, Department of Chemistry, Guru
Jambheshwar University of Science and
Technology, Hisar-125001, Haryana,
India.
Email: jaya.gju@gmail.com
Funding information
Department of Science and Technology,
New Delhi; Haryana State Council for
Science and Technology, Grant/Award
Number: 2118
K E Y W O R D S
anticancer, antimicrobial, hydrazides, indole, pentacoordianted
1 | INTRODUCTION
The predominant treatment for cancer include chemo-
therapy, surgery, radiation, immunotherapy etc. but the
Cancer is an imminent “human disaster” which causes
human mortality and morbidity. It is the unconditional
growth of tissues with manifold etiologies and constant
combination of genetics or epigenetic alterations.[1,2] The
study of cancer treatments hold promises for budding
effective cancer therapies. From the last few years, medic-
inal chemistry has gained attention due to momentous
achievements in cancer therapeutics and diagnostics.[3]
fundamental treatment for cancer is based on chemother-
apy that include the use of different natural and synthetic
chemical entities.[4–7] In this context, Pt (II) metallo-
drugs are recognized anticancer drugs which attained
world-wide clinical approval but these drugs have some
limitations including high toxicity, different side effects,
narrow range of activity and resistance problem.[8,9] So to
improve the clinical efficacy and undesirable side effects,
Appl Organomet Chem. 2020;e5815.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5815

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DEVI ET AL.
a huge number of organometallic compounds have been
assessed for anticancer activity.
indole-3-butyric
acid,
salicylaldehyde,
5-nitrosalicylaldehyde, 4-N,N-diethylsalicylaldehyde and
3,5-dibromosalicylaldehyde were commercially available
from Sigma Aldrich and were used without purification.
The solvents obtained were dried according to the litera-
ture procedure.[40] The melting points were determined
by capillary method using electrical heating coil appara-
tus. Shimadzu IR affinity-I 8000 FT-IR spectrophotome-
ter was used for recording the IR spectra using KBr
Organotin (IV) complexes have established them-
selves as an effective candidates in oncology with amaz-
ingly good IC50 values.[10–14] Earlier, organotin
(IV) complexes received appreciable attention due to
their potent biological activities, industrial, catalytic and
agriculture applications. Recently, a large number of
organotins have been synthesized and tested for antican-
cer activities. The organotin moiety is decisive for cyto-
toxicity, DNA cleavage, antimicrobial, anti-inflammatory,
analgesic, antioxidant, antiHIV etc.[15–20]
The ligand scaffolds also play a key role in the chemo-
therapy. Schiff base ligands having hydrazide groups are
considered as “privileged ligands” and used widely due to
their easy synthetic procedure, good solubility and their
novel structural features.[21–24] Schiff base ligands with
indole hydrazide unit have proven to possess good biolog-
ical application like antimicrobial, anticonvulsant, antihy-
pertensive, antiplatelet aggregation, and HIV-1 reverse
transcriptase inhibitor activities.[25–34] Indoles are widely
distributed heterocyclic compounds having medicinal
importance e.g.- Tryptophan, a natural occurring essential
amino acid which is used as precursor for auxin (indole-
3-acetic acid-IAA), a plant regulating hormone and used
as secondary metabolites, vincristine and vindesine, natu-
ral indole alkaloids is used in treatment of leukemia and
as antitumor agent, brassinin which is used against micro-
organism and mitomycin is natural antibiotic used as
anticancer and DNA cross linking agents.[35–39]
pellets in the range of 400–4,000 cm−1. H, 13C and 119Sn
1
NMR were recorded on a Bruker Avance II 400 MHz
Spectrometer by using CDCl3 and DMSO as solvent with
tetramethylsilane and tetramethyltin as standard. The
value of chemical shifts (δ) are reported in ppm and cou-
pling constants (J) values in Hz and the multiplicities of
signals are given as s = singlet, d = doublet, t = triplet,
m = multiplet. The chemical shift value for the solvents
1
CDCl3 and DMSO in H NMR appeared at δ 7.25 and δ
3.0, 2.5 ppm and 13C NMR were present at δ 77.0 and
40.0 ppm. Absorption spectra were measured in DMSO
on UV- Vis–NIR Varian Cary – 5,000 spectrometer at
room temperature. The electrical conductance was
recorded in conductivity bridge type model- 306 Systronic
at room temperature by using DMF as solvent. Mass
spectra were recorded in methanol and DMSO solvent by
using SCIEX-QTOF instrument. Thermal gravimetric
analysis (TGA) was measured by using EXSTAR TG/DTG
ꢀ
6300 at a heating rate of 10 C/min under high purity
nitrogen atmosphere.
Keeping in view the medicinal and biological activi-
ties of indole hydrazides and the impending application
of organotins, here we join both the moieties in the sea-
rch for designing biologically active candidates that could
belligerently work against microbes and have some
potential application in pharmacology. In the present
study, we have synthesized diorganotin (IV) complexes of
indole-3-butyric hydrazide. Characterization the com-
pounds were done by IR, 1H NMR, 13C NMR, 119Sn
NMR, Mass, UV–vis and TGA methods. The in vitro anti-
microbial activity of compounds was investigated with
four bacterial and two fungal cultures. Antitumor activity
of synthesized compounds against two human cancer cell
lines (A549 and MCF7) and one normal human cell line
(IMR90) is evaluated and discussed.
2.2 | Synthesis of indole-3-butyric
hydrazide precursor
The methanolic solution (35 ml) of indole-3-butyric acid
(5 g) was refluxed with 5 ml of concentrated sulphuric
acid for 5 hr by using the dean stark apparatus to remove
excess of water obtained during the reaction. The ester
formed was extracted by using the dichloromethane and
then refluxed with the methanolic solution of hydrazine
hydrated for 2 hr, which resulted in the formation of
indole-3-butyric hydrazide (Scheme 1). The reddish black
color hydrazide formed was recrystallized from hot meth-
anol to get the pure product.
Synthesis of Schiff base ligands (1–4): The 35 ml
of hot methanolic solution of indole-3-butyric hydrazide
(0.651 g, 3 mmol) was refluxed with methanolic
2 | EXPERIMENTAL
solution of salicyaldehyde (0.3 ml,
H2L1/5-nitrosalicaldehyde
(0.501 g,
3
3
mmol)
mmol)
2.1 | Material and instrumentation
H2L2/4-(N,N diethyl)salicaldehyde (0.579 g, 3 mmol)
H2L3/3,5-dibromosalicaldehyde (0.83 g, 3 mmol) H2L4
(Scheme 2). The colored product was obtained after
refluxing the above solution for 30–40 min. The product
All the chemical reaction was carried out in anhydrous
condition. The reagents
-
diorganotindichloride,

DEVI ET AL.
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SCHEME 1 Synthesis of Indole-3-butyric
hydrazide from indole-3-butyric acid
SCHEME 2 Synthesis of hydrazide
Schiff base ligands (1–4) and their
diorganotin (IV) complexes (5–20)
were recrystallised from chloroform and methanol to
obtain the pure ligands.
13.65, MS: m/z (M+) Cacld. for C19H18N4O4: 366.13;
1
found: 367.15 (M + H)+. H NMR [400 MHz, CDCl3 δ
[1]
N0-(2-hydroxybenzylidene)-4-(1H-indole-3-yl)
(ppm)]: 12.06 (s, 1H, N-H), 11.98 (s, 1H, N-H), 10.88 (s,
butanehydrazide, H2L1 - Yield: 91%, yellow solid; M.p.:
1H, O-H) 9.39 (s, 1H,- N=C-H), 7.80–7.81 (1H, d, C4-Ar-
−1
3
170-174 C, Conductivity: (ohm cm2 mol−1) in DMF:
H, JH,H = 7.71 Hz), 7.77–7.76 (1H, d, C6-Ar-H,
ꢀ
13.05, MS: m/z (M+) Cacld. for C19H19N3O2: 321.14;
4JH,H
3JH,H
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
=
=
2.24 Hz), 7.63–7.60 (1H, d, C3-Ar-H,
7.7 Hz), 7.53–7.51 (1H, d, C4’-Ar-H,
7.67 Hz), 7.34–7.32 (1H, d, C7’-Ar-H,
8.07 Hz), 7.14–7.13 (1H, d, C2’-Ar-H,
2.34 Hz), 7.08–7.04 (1H, t, C6’-Ar-H,
6.98 Hz), 6.99–6.95 (1H, t, C5’-Ar-H,
found: 322.15 (M + H)+. H NMR [400 MHz, CDCl3 δ
1
(ppm)]: 11.59 (s, 1H, N-H), 11.22 (s, 1H, N-H), 10.78 (s,
1H, O-H) 8.33 (s, 1H,- N=C-H), 7.54–7.47 (3H, m, C3,4,4’
-
Ar-H), 7.34–7.32 (1H, d, C7’-Ar-H), 7.13–7.12 (1H, d, C2’-
Ar-H), 7.08–7.04 (1H, m, C6’-Ar-H), 6.99–6.95 (1H, t, C5’-
3
Ar-H), 6.91–6.89 (2H, d, C5,6-Ar-H, JH,H = 7.84 Hz),
3JH,H = 6.98 Hz), 2.75–2.71 (2H, m), 2.67–2.64 (2H, t,
3
3
2.77–2.71 (3H, m), 2.67–2.63 (1H, t, JH,H = 7.46 Hz),
3JH,H = 7.47 Hz), 2.50–2.47 (2H, t, JH,H = 7.50 Hz): 13C
3
2.30–2.27 (2H, t, JH,H = 7.44 Hz): 13C NMR [100 MHz,
NMR [100 MHz, CDCl3, δ (ppm)]: 174.40 (C=O), 168.91
(HC=N), 157.75 (C-OH), 34.19, 26.18, 25.64 (aliphatic
carbon). FT-IR (v, cm−1): 3394 (N-H, indole ring), 3,292
(N-H), 3,062 (O-H, br), 1,703 (C=O), 1,610 (C=N, m),
1,265 (C-OH).
CDCl3, δ (ppm)]: 174.22 (C=O), 168.53 (HC=N), 157.30
(C-OH), 34.16, 26.27, 25.62 (aliphatic carbon). FT-IR (v,
cm−1): 3390 (N-H, indole ring), 3,287 (N-H), 3,065 (O-H,
br), 1,708 (C=O), 1,609 (C=N, m), 1,260 (C-OH).
[2] N0-(2-hydroxy-5-nitrobenzylidene)-4-(1H-indole-
3-yl)butanehydrazide, H2L2 - Yield: 93%, yellow solid; M.
p.: 172-175ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF:
[3] N0-(5-diethylamino)-2-hydroxybenzylidene-4-(1H-
indole-3-yl)butanehydrazide, H2L3 - Yield: 89%, red solid;
M.p.: 167-169 ꢀC, Conductivity: (ohm−1 cm2 mol−1) in

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DEVI ET AL.
DMF: 12.48, MS: m/z (M+) Cacld. for C23H28N4O2:
[5] Me2SnL1: Yield: 78%, yellow solid; M.p.: 160-162
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 12.33, MS:
m/z (M+) Cacld. for C21H23N3O2Sn: 469.00; found: 470.01
1
393.22; found: 394.23 (M + H)+. H NMR [400 MHz,
CDCl3 δ (ppm)]: 11.36 (s, 1H, N-H), 11.27 (s, 1H, N-H),
1
10.78 (s, 1H, O-H) 8.11 (s, 1H,- N=C-H), 7.53–7.51 (d, 1H,
(M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]: 11.99 (s,
3
C4’-Ar-H, JH,H = 7.76 Hz), 7.34–7.32 (1H, d, C7’-Ar-H,
1H, N-H), 8.60 (s, 1H,- N=C-H), 7.65–7.63 (1H, d, C4’-Ar-
3JH,H = 8.04 Hz), 7.15–7.12 (2H, m, C6,2’-Ar-H), 7.08–7.04
H, JH,H = 7.84 Hz), 7.38–7.31 (2H, m, C3,4-Ar-H),
3
3
(1H, t, C6’-Ar-H, JH,H = 8.04 Hz), 6.99–6.95 (1H, m, C5’-
7.22–7.18 (1H, m, C7’-Ar-H), 7.16–7.13 (1H, m, C2’-Ar-H),
7.04–7.03 (1H, d, C6’-Ar-H, 4JH,H = 1.4 Hz), 6.93–6.91 (1H,
m, C5,6-Ar-H), 6.77–6.74 (1H, m, C5’-Ar-H), 2.86–2.83 (2H,
Ar-H), 6.25–6.22 (1H, dd, C5-Ar-H, J = 8.76, 2.4 Hz),
4
6.09–6.091 (1H, d, C3-Ar-H, JH,H = 2.2 Hz), 2.74–2.70
(2H, m), 2.58–2.55 (1H, t, 3JH,H = 7.44 Hz), 2.26–2.22 (2H,
t, JH,H = 7.6 Hz), 2.43–2.40 (2H, t, JH,H = 7.44 Hz),
2.12–2.05 (2H, m), 0.79 (s, 6H, Me). 13C NMR [100 MHz,
CDCl3. δ (ppm)]: 169.03 (HC=N), 166.27 (N=C-OH),
159.86 (C-OH), 34.33, 26.23, 25.67 (aliphatic carbon), 8.51
(Me). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]: −130.43.
FT-IR (v, cm−1): 3392 (N-H, indole ring, br), 1,601 (C=N,
m), 1,240 (C-O), 712 (Sn-O), 526 (Sn-N), 423 (Sn-C).
3
3
3
t, JH,H = 7.44 Hz), 1.98–1.92 (2H, m), 1.11–1.07 (9H, t,
3JH,H = 7 Hz): 13C NMR [100 MHz, CDCl3, δ (ppm)]:
172.13 (C=O), 168.14 (HC=N), 159.96 (C-OH), 44.22,
44.27, 97.94 (N(C2H5)2, 34.16, 26.33, 24.79 (aliphatic car-
bon). FT-IR (v, cm−1): 3382 (N-H, indole ring), 3,205 (N-
H), 3,054 (O-H, br), 1,695 (C=O), 1,614 (C=N, m), 1,253
(C-OH).
[6] Et2SnL1: Yield: 75%, yellow solid; M.p.: 161-163 ꢀC,
Conductivity: (ohm−1 cm2 mol−1) in DMF: 12.06, MS: m/z
(M+) Cacld. for C23H27N3O2Sn: 497.11; found: 598.13
[4]
indole-3-yl)butanehydrazide, H2L4 - Yield: 93%, yellow
solid; M.p.: 172-174ꢀC, Conductivity: (ohm−1 cm2 mol−1
N0-(3,5-dibromo-2-hydroxybenzylidene)-4-(1H-
1
)
(M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]: 11.95 (s,
in DMF: 14.01, MS: m/z (M+) Cacld. for C19H17Br2N3O2:
476.96; found: 477.98 (M + H)+.1H NMR [400 MHz,
CDCl3 δ (ppm)]: 12.65 (s, 1H, N-H), 12.00 (s, 1H, N-H),
10.79 (s, 1H, O-H) 8.25 (s, 1H,- N=C-H), 7.808–7.803 (1H,
1H, N-H), 8.62 (s, 1H,- N=C-H), 7.63–7.61 (1H, d, C4’-Ar-
H, JH,H = 7.84 Hz), 7.38–7.31 (2H, m, C3,4-Ar-H),
3
7.22–7.18 (1H, m, C7’-Ar-H), 7.16–7.13 (1H, m, C2’-Ar-H),
7.03–7.02 (1H, d, C6’-Ar-H, 4JH,H = 1.4 Hz), 6.97–6.95 (1H,
m, C5,6-Ar-H), 6.89–6.85 (1H, m, C5’-Ar-H), 2.86–2.83 (2H,
4
d, C4-Ar-H, JH,H = 2.36 Hz), 7.77–7.76 (1H, d, C6-Ar-H,
4JH,H
3JH,H
3JH,H
4JH,H
=
=
=
=
2.36 Hz), 7.53–7.51 (1H, d, C4’-Ar-H,
7.53 Hz), 7.34–7.32 (1H, d, C7’-Ar-H,
8.04 Hz), 7.14–7.13 (1H, d, C2’-Ar-H,
t, JH,H = 7.6 Hz), 2.45–2.42 (2H, t, JH,H = 7.34 Hz),
2.15–2.10 (2H, m), 1.23–1.27 (m, 4H), 0.83–0.85 (t, 6H,
3JH,H = 7.56 Hz). 13C NMR [100 MHz, CDCl3. δ (ppm)]:
169.37 (HC=N), 166.33 (N=C-OH), 159.91 (C-OH), 35.22,
27.27, 26.54 (aliphatic carbon), 23.34 (Et-C), 7.98 ((Et-C).
119Sn NMR [400 MHz, CDCl3, δ (ppm)]: −150.78. FT-IR (v,
cm−1): 3393 (N-H, indole ring, br), 1,598 (C=N, m), 1,241
(C-O), 714 (Sn-O), 524 (Sn-N), 426 (Sn-C).
3
3
2.12 Hz), 7.08–7.04 (1H, t, C6’-Ar-H,
3
3JH,H = 7 Hz), 6.99–6.95 (1H, t, C5’-Ar-H, JH,H = 7 Hz),
3
2.75–2.71 (3H, t, JH,H = 7.52 Hz), 2.34–2.31 (3H, t,
3JH,H = 7.52 Hz): 13C NMR [100 MHz, CDCl3, δ (ppm)]:
176.42 (C=O), 169.35 (HC=N), 159.87 (C-OH), 34.02,
26.04, 24.71 (aliphatic carbon). FT-IR (v, cm−1): 3403 (N-
H, indole ring), 3,308 (N-H), 3,087 (O-H, br), 1,724
(C=O), 1,617(C=N, m), 1,281 (C-OH).
[7] Bu2SnL1: Yield: 65%, yellow solid; M.p.: 170.172
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 12.74, MS:
m/z (M+) Cacld. for C27H35N3O2Sn: 552.17; found: 553.19
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 11.98 (s,
1H, N-H), 8.60 (s, 1H,- N=C-H), 7.65–7.63 (1H, d, C4’-Ar-
3
2.3 | Synthesis of diorganotin
(IV) complexes (5–20)
H, JH,H = 7.84 Hz), 7.36–7.30 (2H, m, C3,4-Ar-H),
7.24–7.19 (1H, m, C7’-Ar-H), 7.15–7.12 (1H, m, C2’-Ar-H),
4
7.10–7.09 (1H, d, C6’-Ar-H, JH,H = 1.4 Hz), 6.97–6.95
The Schiff base ligand (0.963 g, 3 mmol) H2L1/ (1.098 g,
3 mmol) H2L2/ (1.176 g, 3 mmol) H2L3/ (1.430 g, 3 mmol)
H2L4 was dissolved in tetrahydrofuran solvent (20 ml)
and stirred for 20–30 min by adding ethylamine (0.3 ml)
as base. The above solution was then refluxed with
methyl (0.659 g, 3 mmol), ethyl (0.743 g, 3 mmol), butyl
(0.911 g, 3 mmol) and phenyl (1.031 g, 3 mmol) deriva-
tives of diorganotindichloride (IV) for 7–8 h where white
colored Et3NHCl salt was filtered and solvent was evapo-
rated on the rotary evaporator to get the purified product
(Scheme 2). The different colored solid products isolated
were washed and recrystallized with dried hexane.
(1H, m, C5,6-Ar-H), 6.89–6.85 (1H, m, C5’-Ar-H),
2.85–2.81 (2H, t, JH,H = 7.6 Hz), 2.45–2.42 (2H, t,
3
3JH,H = 7.34 Hz), 2.15–2.10 (2H, m), 1.76–1.71 (m, 4H),
1.39–1.34 (m, 4H), 1.21–1.24 (m, 4H), 0.91–0.88 (6H, t,
3JH,H = 7.83 Hz). 13C NMR [100 MHz, CDCl3. δ (ppm)]:
169.56 (HC=N), 166.54 (N=C-OH), 159.34 (C-OH), 35.21,
28.23, 26.42 (aliphatic carbon), 27.72 (Bu-C), 22.19 (Bu-C),
8.31 (Bu-C). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]:
−214.49. FT-IR (v, cm−1): 3392 (N-H, indole ring, br), 1,600
(C=N, m), 1,244 (C-O), 709 (Sn-O), 526 (Sn-N), 418 (Sn-C).
[8] Ph2SnL1: Yield: 65%, yellow solid; M.p.: 169-171
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 13, MS:

DEVI ET AL.
5 of 17
m/z (M+) Cacld. for C31H27N3O2Sn: 593.11; found: 594.13
(N-H, indole ring, br), 1,604 (C=N, m), 1,234 (C-O),
705 (Sn-O), 525 (Sn-N), 420 (Sn-C).
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 11.93 (s,
1H, N-H), 8.62 (s, 1H,- N=C-H), 7.69–7.66 (3H, m, C3,4,4’
-
[11] Bu2SnL2: Yield: 64%, yellow solid; M.p.: 160-162
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 13.79, MS:
m/z (M+) Cacld. for C27H34N4O4Sn: 598.16; found: 599.17
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 12.47 (s,
1H, N-H), 9.51 (s, 1H,- N=C-H), 7.99–8.02 (1H, dd, C4-
Ar-H), 7.57–7.54 (2H, m, C2’,7’-Ar-H), 7.45–7.41 (8H, Sn-
Ar-H, m), 7.30–7.26 (2H, m, C5,6-Ar-H), 7.19–7.17 (2H,
4
m, C6’,5’-Ar-H, JH,H = 1.4 Hz), 7.09–7.07 (2H, m Sn-Ar-
3
H), 2.86–2.83 (2H, t, JH,H = 7.6 Hz), 2.43–2.40 (2H, t,
3JH,H = 7.44 Hz), 2.12–2.05 (2H, m). 13C NMR [100 MHz,
CDCl3. δ (ppm)]: 169.34 (HC=N), 166.12 (N=C-OH),
159.46 (C-OH), 115–110 (Sn-aromatic carbon), 35.34,
28.37, 26.42 (aliphatic carbon). 119Sn NMR [400 MHz,
CDCl3, δ (ppm)]: −312.04. FT-IR (v, cm−1): 3394 (N-H,
indole ring, br), 1,602 (C=N, m), 1,240 (C-O), 711 (Sn-O),
520 (Sn-N), 419 (Sn-C).
Ar-H, JH,H, JH,H = 7.62, 2.34 Hz), 7.89–7.90 (1H, d, C6-
3
4
4
Ar-H, JH,H = 2.2 Hz), 7.76–7.78 (1H, d, C3-Ar-H,
3JH,H
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
=
7.62 Hz), 7.63–7.61 (1H, d, C4’-Ar-H,
7.52 Hz), 7.52–7.50 (1H, d, C7’-Ar-H,
8.34 Hz), 7.37–7.36 (1H, d, C2’-Ar-H,
1.93 Hz), 7.17–7.14 (1H, t, C6’-Ar-H,
8.31 Hz), 7.04–7.01 (1H, t, C5’-Ar-H,
[9] Me2SnL2: Yield: 70%, yellow solid; M.p.: 161.159
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 11.48,
MS: m/z (M+) Cacld. for C21H22N4O4Sn: 514.06; found:
3JH,H = 7.52 Hz), 3.11–3.07 (4H, m), 2.82–2.76 (2H, m),
1.50–1.47 (10H,m), 1.10–1.07 (4H, m), 0.83–0.77 (4H, m).
13C NMR [100 MHz, CDCl3. δ (ppm)]: 170.34 (HC=N),
166.65 (N=C-OH), 161.02 (C-OH), 37.26, 32.51, 28.17 (ali-
phatic carbon), 27.98 (Bu-C), 25.18 (Bu-C), 20.18 (Bu-C),
9.23 (Bu-C). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]: -
242.28. FT-IR (v, cm−1): 3396 (N-H, indole ring, br), 1,603
(C=N, m), 1,232 (C-O), 711 (Sn-O), 520 (Sn-N), 422 (Sn-C).
[12] Ph2SnL2: Yield: 65%, yellow solid; M.p.: 165-168
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 14.04, MS:
m/z (M+) Cacld. for C31H26N4O4Sn: 638.09; found: 639.11
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 12.43 (s,
1
515.09 (M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]:
12.26 (s, 1H, N-H), 9.45 (s, 1H,- N=C-H), 7.95–7.94
3
(1H, dd, C4-Ar-H, JH,H = 7.83, 1.96 Hz), 7.86–7.85
4
(1H, d, C6-Ar-H, JH,H = 1.96 Hz), 7.70–7.72 (1H, d,
3
C3-Ar-H, JH,H = 7.8 Hz), 7.62–7.60 (1H, d, C4’-Ar-H,
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
7.14 Hz), 7.44–7.42 (1H, d, C7’-Ar-H,
8.14 Hz), 7.20–7.21 (1H, d, C2’-Ar-H,
2.10 Hz), 7.10–7.13 (1H, t, C6’-Ar-H,
8.13 Hz), 7.01–6.98 (1H, t, C5’-Ar-H,
3JH,H = 7.16 Hz), 2.80–2.77 (2H, m), 2.71–2.69 (2H, t,
1H, N-H), 9.46 (s, 1H,- N=C-H), 7.95–7.89 (3H, m, C3,4,6-
3JH,H = 7.84 Hz), 2.53–2.51 (2H, t, JH,H = 7.81 Hz), 0.87
Ar-H, JH,H, JH,H = 7.62, 2.34 Hz), 7.71–7.69 (1H, d, C4’-
3
3
4
(s, 6H, Me). 13C NMR [100 MHz, CDCl3, δ (ppm)]: 170.34
(HC=N), 166.23 (N=C-OH), 160.92 (C-OH), 34.26, 30.33,
26.81, (aliphatic carbon), 8.61 (Sn-C). 119Sn NMR
[400 MHz, CDCl3, δ (ppm)]: −129.81. FT-IR (v, cm−1):
3396 (N-H, indole ring, br), 1,606 (C=N, m), 1,238 (C-O),
709 (Sn-O), 528 (Sn-N), 426 (Sn-C).
Ar-H, JH,H = 7.6 Hz), 7.51–7.49 (1H, d, C7’-Ar-H,
3
3JH,H
4JH,H
3JH,H
=
=
=
8.09 Hz), 7.34–7.33 (1H, d, C2’-Ar-H,
2.2 Hz), 7.18–7.16 (1H, t, C6’-Ar-H,
8.07 Hz), 7.03–7.00 (1H, t, C5’-Ar-H,
3JH,H = 7.6 Hz), 6.95–6.92 (8H, m), 6.84–6.81 (2H, m),
2.83–2.81 (4H, m), 1.94–1.91 (2H, m). 13C NMR
[100 MHz, CDCl3. δ (ppm)]: 170.68 (HC=N), 165.85
(N=C-OH), 160.38 (C-OH), 112–108 (Sn-Ph-C), 35.18,
32.97, 26.81 (aliphatic carbon). 119Sn NMR [400 MHz,
CDCl3, δ (ppm)]: −315. FT-IR (v, cm−1): 3396 (N-H,
indole ring, br), 1,601 (C=N, m), 1,235 (C-O), 709 (Sn-O),
521 (Sn-N), 424 (Sn-C).
[10] Et2SnL2: Yield: 68%, yellow solid; M.p.: 162-159
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 12.13. MS:
m/z (M+) Cacld. for C23H26N4O4Sn: 542.09; found: 543.11
1
(M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]: 12.23
(s, 1H, N-H), 9.48 (s, 1H,- N=C-H), 7.95–7.94 (1H, dd,
3
4
C4-Ar-H, JH,H, JH,H = 7.83, 1.96 Hz), 7.86–7.85 (1H, d,
4
C6-Ar-H, JH,H = 1.96 Hz), 7.71–7.73 (1H, d, C3-Ar-H,
[13] Me2SnL3: Yield: 78%, reddish black solid; M.p.:
3JH,H
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
=
7.8 Hz), 7.61–7.59 (1H, d, C4’-Ar-H,
7.16 Hz), 7.43–7.40 (1H, d, C7’-Ar-H,
8.04 Hz), 7.23–7.24 (1H, d, C2’-Ar-H,
2.2 Hz), 7.11–7.14 (1H, t, C6’-Ar-H,
8.03 Hz), 7.03–6.98 (1H, t, C5’-Ar-H,
160-162 C, Conductivity: (ohm cm2 mol−1) in DMF:
−1
ꢀ
12.79, MS: m/z (M+) Cacld. for C25H32N4O2Sn: 540.15;
found: 541.16 (M + H)+.1H NMR [400 MHz, CDCl3, δ
(ppm)]: 12.03 (s, 1H, N-H), 8.36 (s, 1H,- N=C-H),
7.65–7.63 (d, 1H, C4’-Ar-H, JH,H = 7.8 Hz), 7.38–7.36
(1H, d, C7’-Ar-H, JH,H = 8.00 Hz), 7.21–7.18 (1H, m, C2’-
3
3JH,H = 7.16 Hz), 2.83–2.79 (2H, m), 2.74–2.70 (2H, t,
3
3JH,H = 7.76 Hz), 2.62–2.58 (2H, t, JH,H = 7.73 Hz),
Ar-H), 7.14–7.10 (1H, m, C6 –Ar-H), 7.03 (1H, m, C6’-Ar-
3
1.58–1.54 (6H, t, JH,H = 7.31 Hz), 0.84–0.80 (m, 4H). 13C
H), 6.95–6.93 (1H, d, C5’-Ar-H, JH,H = 8.8 Hz),
3
3
NMR [100 MHz, CDCl3. δ (ppm)]: 170.21 (HC=N),
166.68 (N=C-OH), 160.84 (C-OH), 34.26, 30.33, 26.80,
(aliphatic carbon), 26.11 (Et-C), 8.61 (Et-C). 119Sn NMR
[400 MHz, CDCl3, δ (ppm)]: 159.51. FT-IR (v, cm−1): 3397
6.169–6.163 (1H, d, C5-Ar-H, 4JH,H = 2.2 Hz), 6.147–6.141
4
(1H, d, C3-Ar-H, JH,H = 2.2 Hz), 3.41–3.37 (4H, q,
3JH,H = 7 Hz), 3.15–3.10 (2H, m), 2.85–2.81 (2H, m),
2.40–2.36 (2H, m), 1.22–1.18 (6H, m), 0.75 (s, 6H, Me).

6 of 17
DEVI ET AL.
13C NMR [100 MHz, CDCl3. δ (ppm)]: 170.64 (HC=N),
167.21(N=C-OH), 159.84 (C-OH), 98.94, 45.80, 44.37
(N(C2H5)2, 34.38, 31.36, 27.36 (aliphatic carbon), 7.98
(Me). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]: −135.02.
FT-IR (v, cm−1): 3384 (N-H, indole ring, br), 1,610 (C=N,
m), 1,248 (C-O), 697 (Sn-O), 510 (Sn-N), 418 (Sn-C).
[14] Et2SnL3: Yield: 73%, black solid; M.p.: 164-166
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 12.53, MS:
m/z (M+) Cacld. for C27H36N4O2Sn: 568.18; found: 569.19
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 11.88 (s,
1H, N-H), 8.38 (s, 1H,- N=C-H), 7.64–7.62 (d, 1H, C4’-Ar-
Ar-H), 7.07–7.04 (2H, m, Sn-Ar-H), 7.02–7.00 (1H, s, C3-
3
Ar-H), 6.88–6.85 (2H, d, C5,6-Ar-H, JH,H = 7.8 Hz),
3
3.48–3.42 (2H, m), 3.33–3.27 (4H, q, JH,H = 7.2 Hz),
2.76–2.72 (2H, t, J = 7.6 Hz), 2.44–2.40 (2H, m), 1.13–1.10
3
(6H, t, JH,H = 7.2 Hz). 13C NMR [100 MHz, CDCl3. δ
(ppm)]: 170.68 (HC=N), 167.54(N=C-OH), 159.70 (C-
OH), 112–104 (Sn-Ph-C), 101.90, 45.86, 44.51 (N(C2H5)2,
34.23, 30.33, 26.67 (aliphatic carbon). 119Sn NMR
[400 MHz, CDCl3, δ (ppm)]: −314.37. FT-IR (v, cm−1):
3387 (N-H, indole ring, br), 1,617 (C=N, m), 1,241 (C-O),
701 (Sn-N) (Sn-O), 513 (Sn-N), 424 (Sn-C).
3
H, JH,H = 7.6 Hz), 7.38–7.36 (1H, d, C7’-Ar-H,
[17] Me2SnL4: Yield: 70%, yellow solid; M.p.: 162-164
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 14.05, MS:
m/z (M+) Cacld. for C21H21Br2N3O2Sn: 624.90; found:
625.93 (M + H)+.1H NMR [400 MHz, CDCl3, δ (ppm)]:
12.73 (s, 1H, N-H), 8.48 (s, 1H,- N=C-H), 8.03–8.02 (1H,
3JH,H = 8.00 Hz), 7.25–7.20 (1H, m, C2’-Ar-H), 7.12–7.08
(1H, m, C6 –Ar-H), 7.02 (1H, m, C6’-Ar-H), 6.95–6.93 (1H,
3
d, C5’-Ar-H, JH,H = 8.8 Hz), 6.17–6.16 (1H, d, C5-Ar-H,
4JH,H
=
2.2 Hz), 6.15–6.14 (1H, d, C3-Ar-H,
3
4
4JH,H = 2.2 Hz), 3.38–3.35 (4H, q, JH,H = 7.32 Hz),
d, C4-Ar-H, JH,H = 2.4 Hz), 7.91–7.90 (1H, d, C6-Ar-H,
3.22–3.18 (2H, m), 2.73–2.67 (2H, m), 2.40–2.36 (2H, m),
4JH,H
3JH,H
3JH,H
=
=
=
2.4 Hz), 7.68–7.67 (1H, d, C4’-Ar-H,
7.74 Hz), 7.43–7.41 (1H, d, C7’-Ar-H,
8.01 Hz), 7.21–7.19 (1H, d, C2’-Ar-H,
3
1.34–1.28 (6H, m), 1.18–1.13 (6H, t, JH,H = 7.68 Hz),
0.80–0.76 (4H, m). 13C NMR [100 MHz, CDCl3. δ (ppm)]:
170.91 (HC=N), 168.41(N=C-OH), 159.83 (C-OH), 99.03,
45.91, 44.63 (N(C2H5)2, 37.28, 33.59, 28.95 (aliphatic car-
bon), 24.19 (Et-C), 8.37 (Et-C). 119Sn NMR [400 MHz,
CDCl3, δ (ppm)]: −162.73. FT-IR (v, cm−1): 3385 (N-H,
indole ring, br), 1,612 (C=N, m), 1,243 (C-O), 691 (Sn-O),
512 (Sn-N), 419 (Sn-C).
4JH,H = 2.3 Hz), 7.08–7.04 (1H, t, C6’-Ar-H, 3JH,H = 7 Hz),
6.97–6.93 (1H, t, C5’-Ar-H, 3JH,H = 7.2 Hz), 2.87–2.84 (3H,
3
3
t, JH,H = 7.6 Hz), 2.45–2.41 (3H, t, JH,H = 7.6 Hz), 0.81
(s, 6H, Me). 13C NMR [100 MHz, CDCl3. δ (ppm)]: 171.72
(HC=N), 169.28 (N=C-OH), 161.65 (C-OH), 35.71, 31.28,
26.18 (aliphatic carbon) 8.47 (Me). 119Sn NMR [400 MHz,
CDCl3, δ (ppm)]: −135.60. FT-IR (v, cm−1): 3408 (N-H,
indole ring, br), 1,610 (C=N, m), 1,272 (C-O), 720 (Sn-O),
542 (Sn-N), 431 (Sn-C).
3
ꢀ
[15] Bu2SnL : Yield: 63%, red solid; M.p.: 165-167 C,
Conductivity: (ohm−1 cm2 mol−1) in DMF: 13, MS: m/z
(M+) Cacld. for C31H44N4O2Sn: 624.24; found: 625.26
(M + H)+. 1H NMR [400 MHz, CDCl3, δ (ppm)]: 11.72 (s,
1H, N-H), 8.37 (s, 1H,- N=C-H), 7.65–7.64 (d, 1H, C4’-Ar-
[18] Et2SnL4: Yield: 63%, yellow solid; M.p.: 165-168
ꢀC, Conductivity: (ohm−1 cm2 mol−1) in DMF: 13.97, MS:
m/z (M+) Cacld. for C23H25Br2N3O2Sn: 652.93; found:
3
H, JH,H = 7.6 Hz), 7.38–7.34 (2H, m, C7’, 2’-Ar-H),
1
7.10–7.07 (1H, m, C6 –Ar-H), 7.05 (1H, m, C6’-Ar-H),
653.92 (M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]:
3
6.97–6.95 (1H, d, C5’-Ar-H, JH,H = 8.8 Hz), 6.25–6.24
12.75 (s, 1H, N-H), 8.47 (s, 1H,- N=C-H), 7.99–7.98 (1H,
(1H, d, C5-Ar-H, 4JH,H = 2.4 Hz), 6.18–6.17 (1H, d, C3-Ar-
d, C4-Ar-H, JH,H = 2.34 Hz), 7.91–7.90 (1H, d, C6-Ar-H,
4
4
3
H, JH,H = 2.4 Hz), 3.43–3.39 (4H, q, JH,H = 7.76 Hz),
3.30–3.25 (2H, m), 2.84–2.80 (2H, m), 2.45–2.40 (2H, m),
1.85–1.79 (6H, m), 1.47–1.40 (10H, m), 1.08–1.04 (4H, m),
0.73–0.69 (4H, m). 13C NMR [100 MHz, CDCl3. δ (ppm)]:
170.93 (HC=N), 168.45(N=C-OH), 159.96 (C-OH),
101.37, 51.37, 47.39 (N(C2H5)2, 41.28, 35.19, 31.86 (ali-
phatic carbon), 29.77 (Bu-C), 25.35 (Bu-C), 20.29 (Bu-C),
8.94 (Bu-C). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]:
−223.45. FT-IR (v, cm−1): 3384 (N-H, indole ring, br),
1,614 (C=N, m), 1,240 (C-O), 695 (Sn-O), 510 (Sn-N),
422 (Sn-C).
4JH,H
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
=
2.34 Hz), 7.70–7.72 (1H, d, C4’-Ar-H,
7.8 Hz), 7.45–7.43 (1H, d, C7’-Ar-H,
8.20 Hz), 7.21–7.19 (1H, d, C2’-Ar-H,
2.3 Hz), 7.07–7.05 (1H, t, C6’-Ar-H,
7.2 Hz), 6.97–6.93 (1H, t, C5’-Ar-H,
3JH,H = 7.2 Hz), 2.88–2.84 (3H, t, 3JH,H = 8 Hz), 2.45–2.40
(3H, t, 3JH,H = 8 Hz), 1.43–1.41 (6H, m), 0.82–0.79 (q, 4H,
3JH,H = 8.27 Hz). 13C NMR [100 MHz, CDCl3. δ (ppm)]:
171.66 (HC=N), 169.64 (N=C-OH), 161.04 (C-OH), 35.20,
31.33, 26.13 (aliphatic carbon), 24.72 (Et-C), 8.83 (Et-C).
119Sn NMR [400 MHz, CDCl3, δ (ppm)]: −167.86. FT-IR
(v, cm−1): 3408 (N-H, indole ring, br), 1,611 (C=N, m),
1,270 (C-O), 719 (Sn-O), 540 (Sn-N), 428 (Sn-C).
[16] Ph2SnL3: Yield: 68%, reddish black solid; M.p.:
−1
163-165 C, Conductivity: (ohm cm2 mol−1) in DMF:
ꢀ
12.42, MS: m/z (M+) Cacld. for C35H36N4O2Sn: 664.18;
[19] Bu2SnL4: Yield: 71%, whitish yellow solid; M.p.:
found: 665.19 (M + H)+. H NMR [400 MHz, CDCl3, δ
167-169 C, Conductivity: (ohm cm2 mol−1) in DMF:
1
−1
ꢀ
(ppm)]: 11.42 (s, 1H, N-H), 8.51 (s, 1H,- N=C-H),
13.76, MS: m/z (M+) Cacld. for C27H33Br2N3O2Sn: 708.99;
found: 710.02 (M + H)+.1H NMR [400 MHz, CDCl3, δ
(ppm)]: 12.55 (s, 1H, N-H), 8.53 (s, 1H,- N=C-H),
7.63–7.60 (m, 2H, C4’, 5’-Ar-H), 7.54–7.52 (2H, m, C2’,7’
-
Ar-H), 7.42–7.39 (8H, m, Sn-Ar-H), 7.21–7.17 (1H, m, C6’-

DEVI ET AL.
7 of 17
4
8.05–8.04 (1H, d, C4-Ar-H, JH,H = 2.12 Hz), 7.93–7.94
poisoning) and two gram negative bacteria - Escherichia
coli (MTCC 732) (causes dysentery and infection in uri-
nary tract) and Pseudomonas aeruginosa (MTCC 424)
(causes soft tissue infection and dermatitis) were used.
The fungal strains used were - Aspergillus niger (MTCC
9933) (weaker immune system and lungs) and Candida
albicans (MTCC 227) (causes tongue piercing).
4
(1H, d, C6-Ar-H, JH,H = 2.12 Hz), 7.74–7.72 (1H, d, C4’-
Ar-H, JH,H = 8 Hz), 7.47–7.45 (1H, d, C7’-Ar-H,
3
3JH,H
4JH,H
3JH,H
=
=
=
8.34 Hz), 7.21–7.19 (1H, d, C2’-Ar-H,
2.3 Hz), 7.15–7.13 (1H, t, C6’-Ar-H,
7.53 Hz), 6.99–6.97 (1H, t, C5’-Ar-H,
3JH,H = 7.6 Hz), 3.04–3.02 (3H, t, JH,H = 7.95 Hz),
3
3
2.77–2.75 (3H, t, JH,H = 7.95 Hz), 1.72–1.70 (t, 6H,
3JH,H = 7.34 Hz), 1.34–1.30 (8H, m), 0.75–0.72 (t, 4H,
3JH,H = 8.14 Hz Hz). 13C NMR [100 MHz, CDCl3. δ
(ppm)]: 171.89 (HC=N), 169.04 (N=C-OH), 161.47 (C-
OH), 37.17, 34.49, 28.85 (aliphatic carbon), 26.29 (Bu-C),
24.69 (Bu-C), 19.90 (Bu-C), 8.52 (Bu-C). 119Sn NMR
[400 MHz, CDCl3, δ (ppm)]: −247.55. FT-IR (v, cm−1):
3406 (N-H, indole ring, br), 1,613 (C=N, m), 1,269 (C-O),
715 (Sn-O), 538 (Sn-N), 433 (Sn-C).
2.4.3 | Compounds concentration
The compounds were prepared by dissolving 5 mg in
5 ml of DMSO as a stock solution. Then 1 ml of stock
solutions was diluted with the 9 ml of DMSO to form
concentration up to 100 μg/ml.[41]
4
ꢀ
[20] Ph2SnL : Yield: 61%, red solid; M.p.: 163-164 C,
Conductivity: (ohm−1 cm2 mol−1) in DMF: 14.38, MS:
m/z (M+) Cacld. for C31H25Br2N3O2Sn: 748.93; found:
2.4.4 | Culture and preservation of
microbes
1
749.95 (M + H)+. H NMR [400 MHz, CDCl3, δ (ppm)]:
12.52 (s, 1H, N-H), 8.60 (s, 1H,- N=C-H), 7.99–7.91 (2H,
m), 7.74–7.72 (1H, d, C4’-Ar-H, JH,H = 8 Hz), 7.45–7.38
(8H, m, Sn-Ar-H), 7.34–7.31 (1H, d, C7’-Ar-H,
Different conditions were used for growth of bacterial
and fungal strains. The bacteria were subcultured on the
nutrient broth (1.3 g) and fungus on Potato dextrose
broth (2.4 g) in the 100 ml of distilled water and
autoclaved at 15 psi for 30–35 min. The cultures were
3
3JH,H
3JH,H
4JH,H
3JH,H
=
=
=
=
8.05 Hz), 7.28–7.26 (2H, t, Sn-Ar-H,
8.46 Hz), 7.20–7.19 (1H, d, C2’-Ar-H,
2.0 Hz), 7.10–7.08 (1H, t, C6’-Ar-H,
7.62 Hz), 6.99–6.97 (1H, t, C5’-Ar-H,
ꢀ
incubated at 37 ꢀC for 24 hr and 48 hr at 27 C for bacte-
rial and fungal culture. Then transferred 1 ml of the
above bacterial/fungal culture to the saline solution and
used it for the antibacterial and antifungal activity.[42]
3JH,H = 7.6 Hz), 2.89–2.86 (3H, t, 3JH,H = 8 Hz), 2.74–2.72
(3H, t, JH,H = 8 Hz). 13C NMR [100 MHz, CDCl3. δ
3
(ppm)]: 171.67 (HC=N), 168.72 (N=C-OH), 161.12 (C-
OH), 112–104 (Ph-C), 34.18, 32.72, 26.61 (aliphatic car-
bon). 119Sn NMR [400 MHz, CDCl3, δ (ppm)]: −324.47.
FT-IR (v, cm−1): 3410 (N-H, indole ring, br), 1,615 (C=N,
m), 1,269 (C-O), 716 (Sn-O), 538 (Sn-N), 431 (Sn-C).
2.4.5 | Determination of antibacterial and
antifungal assay
Serial dilution method was used for carrying the antimi-
crobial activity and minimum inhibitory concentrations
(MIC) of the compounds were calculated. In serial dilu-
tion method, 1 ml of stock solution was added to the test
tube containing 1 ml of broth and serially diluted it to
3.125 μg/ml concentration. After serial dilution of each
test tube, above prepared microbes culture was inocu-
lated and plugged with the cotton. Then the test tubes
were put in the incubator at controlled temperature for
fixed time. The MICs of the compounds were calculated
after the definite interval of time. The activity was per-
formed in duplicate to minimize the error and their mean
value is represented here.
2.4 | Biological application
2.4.1 | Antimicrobial activity
The synthesized compounds (1–20) were evaluated for
the in vitro antibacterial and antifungal activity choosing
four bacterial and two fungal cultures. Ciprofloxacin and
fluconazole were used as positive control and DMSO as
negative control for antibacterial and antifungal activity.
2.4.2 | Microbes used
For carrying out the antibacterial activity of synthesized
compounds, two gram positive bacteria -Staphylococcus
aureus (MTCC 2901) (causes food poisoning and skin
syndrome) and Bacillus subtilis (NCIM 2063) (causes food
2.4.6 | Cytotoxicity assay
Anticancer activity of the synthesized compounds (1–20)
was evaluated by measurement of in vitro growth

8 of 17
DEVI ET AL.
inhibition of tumor cells in 96 well plates by cell
mediated reduction of tetrazolium salt to water insolu-
ble formazan crystals using doxorubicin as a standard
drug. The cytotoxicity was tested against a panel of
three different human cell lines: A549 derived from
human alveolar adenocarcinoma epithelial cells (ATCC
No. CCL-185); MCF7 derived from human breast ade-
nocarcinoma cells (ATCC No. HTB-22) and IMR90
derived from human normal lung cells (ATCC
No. CCL-186), using the MTT colorimetric assay.[43]
For the evaluation of effect of synthesized compounds
on the viability of tumor as well as normal cell lines,
the absorbance was observed at wavelength of 540 nm
on a multimode reader (InfiniteM200, Tecan, Man-
nedorf, Switzerland), followed by plotting of dose
response curves for the synthesized compounds and
standard after making correction by subtracting the
background absorbance with that of the blanks. IC50
values were calculated from the plotted absorbance
data of the dose response curves. All the experiments
were carried out in triplicate and the results were
reported as IC50 values (in μM) expressed as the
3.2 | Electronic spectra
The electronic transition involved in the Schiff base
ligands and their diorganotin (IV) complexes was studied
with the help of UV–vis spectra. The electronic spectra of
the ligands showed π ! π* and n ! π* transitions
around 254–262 and 348–367 nm. These bands were
slightly shifted to higher wavelength on complexation. A
new band on complexation appeared at the 415–400 nm
due to the ligand to metal charge transfer which con-
firmed the complexation of Schiff base ligands with the
metal centre.[45,46]
3.3 | IR spectra
The most explicit band in the IR spectrum which ascer-
tain about the complexation was the disappearance of the
ν(N–H) and ν(O–H) stretching bands present in the
ligands at 3205–3308 cm−1 and 3,059–3,087 cm−1, respec-
tively. The binding in the complexes was studied by com-
paring the ν(C=N) and ν(N–N) stretching frequency of
complexes and ligands. In Schiff base ligands, the
ν(C=N) and ν(N–N) stretching bands appeared at
1609–1617 cm−1 and 987–1,009 cm−1 but in complexes,
they slightly got shifted to lower frequency which
supported the coordination of azomethine nitrogen to the
tin (IV) metal centre.[47,48] In ligands ν(C=O) stretching
band was present at 1695–1724 cm−1, got disappeared in
the complexes which suggested the tautomerisation of
the Schiff bases on complexation. The stretching vibra-
tion band due to the ν(C–O) at 1253–1281 cm−1 got dis-
placed to lower frequency in complexes, postulates the
formation of Sn-O bond in the complexes. The vibration
mean
SD.
2.4.7 | In Silico study
ADME study was carried out in silico for the prediction
of drug likeness of synthesized compounds. For in silico
study molinspiration online study toolkit (http: //www.
Molinspiration. com/cgi-bin/properties)[44] was used and
bioactivity scores are calculated which are summarized
in Table 2.
stretching band in complexes at 691–720 cm−1
,
3 | RESULTS AND DISCUSSION
3.1 | Chemistry
510–542 cm−1 and 418–433 cm−1 due to the Sn-O, Sn-N
and Sn-C bond confirmed coordination of tin metal with
oxygen, nitrogen and carbon atom (Fig. S1, S2).[49] After
studying all the vibration bands of IR spectra, it was
suggested that the complexes have pentacoordinated
geometry around the tin metal and Schiff bases have tri-
dentate (ONO) nature.
In the present work, hydrazide Schiff base ligands
(1–4) were synthesized by the reaction of indole-
3-butyric hydrazide with the salicylaldehyde and its
derivatives in methanol solvent. Sixteen new
diorganotin (IV) complexes (5–20) were prepared by
reaction of hydrazide Schiff base ligands with R2SnCl2
in 1:1 molar ratio by adding triethylamine as base.
The spectroscopic data describes the synthesized
diorganotin (IV) complexes to have pentacoordinated
geometry with the tridentate ligands (ONO). All
diorganotin (IV) complexes were stable in air, obtained
in good yield, non-volatile, non-electrolytic in nature
and are soluble in DMSO, DMF, THF and CHCl3
solvent.
1
3.4 | H NMR spectra
1
In the H NMR spectra of Schiff base ligands, the most
prominent signal is present at δ 11.22–12.00 ppm and
10.78–10.88 ppm due to O=C-NH and OH proton, respec-
tively, which got disappeared on complexation. The
tautomerization of Schiff base ligands and coordination
of enolic oxygen with the tin (IV) metal center was
suggested in the IR spectra but the confirmation was

DEVI ET AL.
9 of 17
given by the disappearance of O=C-NH signal in proton
NMR.[50,51] The signal at δ 8.11–9.39 ppm due to
azomethine proton (N=CH) got shifted downfield on
complexation due to the donation of electron density
from azomethine nitrogen to tin (IV) metal atom. The
3J(119Sn-1H) coupling gives tin satellite peaks with the
azomethine proton signals due to coupling of azomethine
proton with tin metal and comes in the range of
43–48 Hz, confirms the coordination of nitrogen with tin
(IV) metal and formation of Sn-N bond. The N-H proton
of the indole ring display signal at δ 11.36–12.65 ppm that
remains unaffected on complexation, established its non-
coordination with the metal centre.[52] The aromatic pro-
tons of the Schiff base ligands at δ 6.09–7.80 ppm were
unaffected or very less affected on the complex formation.
Aliphatic signals present at δ 2.22–2.75 ppm gets shifted
downfield during the complex formation (Fig. S3-S6).
The 1H NMR of diorganotin (IV) complexes show
some additional signals due to the presence of alkyl/aryl
groups directly attached to the tin (IV) metal. A singlet of
Sn-CH3 at δ 0.75–0.81 ppm with tin satellite peaks due to
2J(119Sn-1H) coupling has values in range of 72–76 Hz,
which is indicative of the five coordinated tin
(IV) species.[53,54] The methyl proton in the diethyl com-
plexes appears as triplet at δ 1.13–1.43 ppm and methy-
chemical shift value of diethyl and dibutyl carbon falls in
the range of δ 23.34–26.11 ppm, δ 7.98–8.83 ppm and δ
20.18–27.72 ppm, δ 8.31–9.23 ppm. The carbon signals of
phenyl group appended to tin atom at δ 104–115 ppm
(Fig. S13-S16). These new signals confirm the Sn-C bond
in the complexes.
3.6 | 119 Sn NMR
The chemical shift value of 119Sn NMR describes the
coordination number of tin metal. The methyl complexes
in the 119Sn NMR gives the signal at δ − 129.81 to
−135.60 ppm, ethyl complexes resonate at
-
δ
150.78 t0–167.86 ppm, butyl complexes at δ − 214.75 to
−274.55 ppm and phenyl complexes give signals at
δ − 312.04 to −324.47 ppm (Fig. S17-S19). These values of
chemical shift lie in the penta coordinated environment
and all the signals appear as the singlet which confirms
the existence of one isomer or mononuclear complex of
the tin (IV) metal.[57]
3.7 | Mass spectra
lene protons as multiplets in the range of
δ
The molecular weight determination, possible fragmenta-
tion pattern, stability of fragments and isotopic studies
was done with the help of mass spectra. In Figure 1 rep-
resents the mass spectra of compound 3 and 16. In the
mass spectra of (H2L3) 3 the M + H ion peak and base
peak was observed at m/z 393.22 which was same as the
calculated value. The medium intensity peak at m/z
394.23 was due to the isotopes of nitrogen [M + H + 15N].
In the mass spectra of complex 16 (Ph2SnL3), the molecu-
lar ion peak of [M + H + 119Sn] is observed at m/z 665.19
and another peak with the a gap of 2 m/z units at m/z
663.19 is attributed to [M + H + 117Sn] molecular ion
and agrees with the isotopic abundance of tin. One addi-
tional peak at m/z 664.19 is due to [M + 119Sn]+.. The
molecular ion peaks observed at m/z 394.23 and 393.22
was due to ligand entity which confirmed the coordina-
tion of tin metal with Schiff base ligands.
0.76–0.85 ppm. The butyl protons in the dibutyl com-
plexes resonates as multiplet and triplet in the range of δ
1.04–1.76 ppm and δ 0.69–0.91 ppm, respectively. In the
diphenyl complexes, the phenyl protons appear at δ
6.22–7.26 ppm (Fig. S7-S10).
The 1H NMR data confirms the tridenticity of the
hydrazide Schiff base ligands (ONO) and their
pentacoordinated environment around the central metal
atom. The NMR data is in good agreement with the
expected molecular structure.
3.5 | 13C NMR spectra
13C NMR spectral data also supports the authenticity of
the proposed structures. The signals for C=O carbon
atom resonate at δ 172.12–176.42 ppm in ligands which
shifted upfield in the complexes supports further the
tautomerization of Schiff base ligands on complexa-
tion.[55] The coordination of Schiff base ligands were fur-
ther strengthened by the azomethine carbon signals at δ
168.14–169.35 ppm in ligands which undergoes down-
field shift in their position on complexation (Fig. S11).[56]
Some new signals in complexes additionally describe
the further coordination of tin metal with alkyl/aryl
groups. The carbon of methyl group in dimethyltin
(IV) derivative is present at δ 7.98–8.61 ppm. The
Molecular ion peak and other characterized peaks
indicate the mononuclear nature of the complexes in 1:1
metal ligand ratio.
3.8 | Thermal studies
Thermogravimetric
curve
for
the
diorganotin
(IV) complexes in the temperature range 28–800 ꢀC high-
lights the percentage mass loss with the temperature
which indicates the volatility and stability of

10 of 17
DEVI ET AL.
FIGURE 1 Mass spectra of
compounds a) H2L3 (3) and b) Ph2SnL3
(16)
compounds.[58] From the TGA curve of Me2SnL2 (9),
three successive mass loss steps take place Figure 2. In
the first step mass loss of 5.57% (calculated 5.34%) at tem-
perature 201-232 ꢀC due to removal of methyl groups
directly attached to the tin (IV) which suggests that the
compound was stable up to 200 ꢀC and complex does not
contain the coordinated as well as lattice water molecule
and the complex was free of moisture. In the second step
a gradual weight loss of 75.79% was noticed at tempera-
3.9 | Antimicrobial activity
Hydrazide Schiff bases and their diorganotin
(IV) complexes (1–20) were screened for the antimicro-
bial activity against four bacterial strain Staphylococcus
aureus, Bacillus subtilis, Escherichia coli, Pseudomonas
aeruginosa and two fungal strains Aspergillus niger and
Candida albicans. The experiments were performed in
duplicate by serial dilution method using ciprofloxacin
and fluconazole as positive standard and DMSO as nega-
tive standard for antibacterial and antifungal activity.
The MIC values were calculated and results are summa-
rized in the Table 1 and Figure 3.
ꢀ
ture 234–398 C due to ligand moiety, agreed with the
estimated mass loss of the calculated value 75.32%. In the
last step, tin oxide remains as residue having 20% mass
which verified tin oxides as the precursor of the com-
plexes. All the complexes follow the same pattern of
decomposition as described above.
The pentacoordinated diorganotin (IV) complexes
have more growth inhibition effect than the free Schiff

DEVI ET AL.
11 of 17
base ligands which have greater than respective starting
precursors. The growth inhibition of microbes increases
with the increase in the concentration of complexes. Gen-
erally, structure activity relationship of the compounds
are discussed on the basis of coordination number, che-
late effects of ligands, substituent attached to the ring,
presence and absence of electron withdrawing and releas-
ing groups, alkyl/aryl groups attached to tin metal, total
charge on the complexes and molecular mass of the com-
pounds.[59,60] The conclusions drawn from the current
activity data is summarised below:
1 By comparing the antimicrobial activity of Schiff base
ligands (1–4) it was found that the H2L4 (4) was most
active (MIC = 0.026 μm/ml) than the other ligands.
The higher activity of the H2L4 was due to the pres-
ence of the electron withdrawing group (bromo) on
the ring and H2L3 (3) was less active
(MIC = 0.127 μm/ml) due to the presence of the elec-
tron releasing group (diethylamine). When no
FIGURE 2 Thermal decomposition curve of complex
Me2SnL2 (9)
TABLE 1
Minimum inhibitory concentration (MIC in μM/ml) of compounds (1–20) against antibacterial and antifungal strains
MIC in μM/ml
Gram +ve bacteria
B.subtilis
Gram –ve bacteria
P.aeruginosa
Fungi
Comp. no.
compounds
H2L1
H2L2
H2L3
H2L4
S.aureus
0.077
0.034
0.127
0.026
0.026
0.025
0.022
0.021
0.024
0.023
0.020
0.019
0.046
0.044
0.040
0.037
0.020
0.019
0.016
0.008
0.0047
-
E. coli
0.077
0.068
0.127
0.026
0.026
0.025
0.044
0.021
0.048
0.023
0.040
0.019
0.046
0.088
0.080
0.037
0.020
0.038
0.016
0.008
0.0047
-
A.niger
0.077
0.068
0.063
0.026
0.026
0.050
0.022
0.042
0.024
0.023
0.020
0.009
0.046
0.044
0.040
0.074
0.010
0.019
0.016
0.008
-
C.albicans
0.077
0.034
0.063
0.026
0.026
0.050
0.022
0.021
0.024
0.023
0.020
0.009
0.046
0.044
0.040
0.037
0.010
0.019
0.016
0.008
-
1
0.077
0.034
0.127
0.026
0.026
0.025
0.022
0.042
0.024
0.023
0.020
0.019
0.046
0.088
0.040
0.037
0.020
0.019
0.016
0.008
0.0047
-
0.077
0.034
0.127
0.026
0.026
0.025
0.044
0.021
0.024
0.023
0.040
0.019
0.092
0.044
0.040
0.037
0.020
0.019
0.016
0.008
0.0047
-
2
3
4
5
Me2SnL1
Et2SnL1
Bu2SnL1
Ph2SnL1
Me2SnL2
Et2SnL2
Bu2SnL2
Ph2SnL2
Me2SnL3
Et2SnL3
Bu2SnL3
Ph2SnL3
Me2SnL4
Et2SnL4
Bu2SnL4
Ph2SnL4
Ciprofloxacin
Fluconazole
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
0.0102
0.0051

12 of 17
DEVI ET AL.
FIGURE 3 Graph showing antimicrobial
activity of the synthesized compounds (1–20)
substituent is attached to the Schiff base ligand as in
bacteria with MIC value in the range of 0.026–-
0.008 μm/ml. For gram negative bacteria, complexes 4,
5, 6, 8, 10, 12, 17, 19 and 20 were MIC in the range of
MIC = 0.026–0.008 μm/ml. The results of antimicro-
bial activity also suggested that the compounds were
more active for fungus as compared to the bacteria.
Compounds 12, 17 and 20 (MIC = 0.010–0.008 μm/ml)
were more active against the fungus. Compound 20
have highest activity (MIC = 0.008 μm/mL) in the
entire series which was nearer to the standard drugs
(ciprofloxacin MIC = 0.0047 μm/ml and fluconazole
MIC = 0.0102 for A. niger and 0.0051 μm/ml for C.
albicans).
compound H2L1 (1), the moderate activity
(MIC = 0.077 μm/mL) or in between the compound
3 and 4. The above data indicates that compounds hav-
ing electronegative groups were more active than the
compounds having the electron releasing groups. The
general trend of the activity for the Schiff base ligands
was: H2L4 > H2L2 > H2L1 > H2L3
2 Activity of complexes increases as compared to the
Schiff base ligands due to the chelation of metal which
results in increase in lipophilic and hydrophobic char-
acter of the compounds as explained in the tweedy
chelation theory. With the increase in the lipophilicity,
complexes easily pass through the lipid bilayer of cell
membrane and blocks the metal binding sites which
results in the disruption of the cell, inhibit the protein
synthesis machinery and biological process of the
cell.[61,62]
The different physiochemical studies were done for
the synthesis of any drugs which is based on their molec-
ular properties. Orally active drug should follow the
Lipinski's rule of five which describe the molecular and
biological properties of the drugs and is essential for the
ADME properties. The Lipinski's rules of five are: molec-
ular weight of the compounds should be ≤500 dalton, the
value of logP to be ≤5, the number of hydrogen bond
donor is ≤5 and hydrogen bond acceptor ≤10. If the vio-
lation of more than 2 rules takes place than the drug is
not an orally active drug.[63]
Molinspiration online (http:/molinspiration.com/cgi-
bin/properties) was used to study the molecular proper-
ties and bioactivity of compounds. The ADME properties
were calculated and presented in the Table 2 and con-
cluded that the synthesized compounds are not violating
more than two rules and can be used as orally active
drugs according to the rule of five.
3 On complexation, the effect of the alkyl/aryl group
attached to tin metal is observed. Complexes having
the
phenyl
ring
have
higher
activity
(MIC = 0.021–0.008 μm/ml) than the butyl, ethyl and
methyl complexes. The higher activity of the phenyl
complexes was due to the delocalisation of the П elec-
tron cloud over the ring. The butyl complexes has
higher activity (MIC = 0.022–0.016 μm/ml) than the
ethyl and methyl complexes which was due to higher
molecular mass of the compound. The above data sig-
nifies that the activity of these compounds were
mainly affected by the presence of alkyl/aryl groups
directly attached with the tin (IV) metal and molecular
mass of compounds. The general order of activity of
the complexes were Ph > Bu > Et ≥ Me.
The value of log P describes about the lipophilicity of
compounds. 4, 7, 11, 15, 16, 19 and 20 compounds does
not show the lipophilic nature (log P) due to its value is
4 Compounds 4, 5, 6, 10, 11, 12, 17, 18, 19 and 20 have
higher activity among all compounds for gram positive

DEVI ET AL.
13 of 17
TABLE 2
Bioactivity Scores of compounds (1–20) by using the molinspiration
C.No
1
Compounds
H2L1
H2L2
H2L3
H2L4
% Abs
82.26
66.45
81.15
82.26
88.68
88.68
88.68
88.68
72.84
72.84
72.84
72.84
87.53
87.53
87.53
87.53
88.64
88.64
88.64
88.64
MW
C log P
4.07
4.00
4.90
5.38
2.47
3.22
5.34
5.86
2.40
3.16
5.28
5.80
3.30
4.05
6.18
6.69
3.99
4.74
6.87
7.39
TPSA
77.48
123.31
80.72
77.48
58.99
58.99
58.99
58.99
104.81
104.81
104.81
104.81
62.23
62.23
62.23
62.23
58.99
58.99
58.99
58.99
n-ON
n-OHNH
n-rot
6
Volume
321.38
366.38
392.50
479.17
468.14
496.20
552.31
592.29
513.14
541.20
597.30
637.28
539.27
567.32
623.43
663.41
625.94
653.99
710.10
750.08
5
8
6
5
5
5
5
5
8
8
8
8
6
6
6
6
5
5
5
5
3
3
3
3
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
279.50
320.83
377.01
333.27
360.76
394.36
461.57
470.45
384.09
417.70
484.90
493.79
440.27
473.87
541.08
549.96
396.53
430.13
497.34
506.23
2
7
3
9
4
6
5
Me2SnL1
Et2SnL1
Bu2SnL1
Ph2SnL1
Me2SnL2
Et2SnL2
Bu2SnL2
Ph2SnL2
Me2SnL3
Et2SnL3
Bu2SnL3
Ph2SnL3
Me2SnL4
Et2SnL4
Bu2SnL4
Ph2SnL4
4
6
6
7
10
6
8
9
5
10
11
12
13
14
15
16
17
18
19
20
7
11
7
7
9
13
9
4
6
10
6
-MW = Molecular weight
-ClogP = Logarithm of partition Coefficient
-TPSA = Topological polar surface area
-n-ON = Number of hydrogen bond acceptor
-n-OHNH = Number of hydrogen bond donor
- n-rot = Number of rotatable bond
more than 5 value.[64] The TPSA value of compounds was
less than 130 Å2 which shows good transport properties
of compounds. The percentage absorption of the com-
pounds was calculated by using the formula % Abs = 109-
(0.345 × TPSA).[65] The value of % absorbance was high
for the complexes as compared to the ligands which sug-
gests better absorption of complexes than respective
ligands.
compared with the activity of the known anticancer drug
doxorubicin which was used as a reference.
Activity data of Schiff base ligands (1–4) suggested
compound 3 (H2L3) to be more potent with lowest IC50
value of 15.4 and 13.9 μM against A549 and MCF7 cell
lines. Schiff base ligand 1 (H2L1) was found to be moder-
ately active with IC50 value of 62.1 and 51.2 μM against
human cancer cell lines and ligand 2 (H2L2) was least
active in the entire series of the compounds.
The results of cytotoxic activity of diorganotin
(IV) complexes (5–20) showed that compound 10
(Et2SnL2) displayed excellent activity with an IC50 value
of 13.4 and 15.2 μM against A549 and MCF7 cell lines,
respectively. The ethyl complexes 14 and 18 showed mod-
erate anticancer activity with IC50 values 29.6, 27.8 and
23.8, 20.5 μM against A549 and MCF7 cell lines. The sig-
nificant feature of ethyl complexes is about 8 fold less
toxic as compared to standard drug doxorubicin against
normal cell line IMR90. Compounds 1, 3, 7, 12, 16 and 19
showed the good cytotoxic activity with IC50 values
3.10 | Cytotoxicity results
The efficiency of the hydrazide Schiff bases and their
diorganotin (IV) complexes (1–20) as anticancer drug has
been tested in vitro on two human cancer cell lines
namely human alveolar adenocarcinoma epithelial cell
line (A549), human breast adenocarcinoma cell line
(MCF7), and human normal lung cell line (IMR90), using
MTT assay. The results of IC50 values of compounds are
summarized in Table 3 and Figure 4. The data was

14 of 17
DEVI ET AL.
TABLE 3
Anticancer activity of synthesized compounds (1–20) against two cancer cell lines (A549, MCF7) and one normal cell line
(IMR90)
IC50 values (μM S.D.)
C.No.
Compounds
H2L1
H2L2
H2L3
H2L4
A549
MCF7
IMR90
1
62.1 0.33
190.5 0.54
15.4 0.34
102.5 0.32
-
51.2 0.21
186.2 0.22
13.9 0.12
101.0 0.18
-
106.8 0.13
198.6 0.56
90.6 0.52
120.3 0.37
-
2
3
4
5
Me2SnL1
Et2SnL1
Bu2SnL1
Ph2SnL1
Me2SnL2
Et2SnL2
Bu2SnL2
Ph2SnL2
Me2SnL3
Et2SnL3
Bu2SnL3
Ph2SnL3
Me2SnL4
Et2SnL4
Bu2SnL4
Ph2SnL4
6
82.4 0.14
77.5 0.34
86.4 0.71
94.1 0.31
13.4 0.23
84.6 0.37
73.1 0.15
85.7 0.23
29.6 0.34
-
79.7 0.34
74.2 0.22
95.7 0.45
91.2 0.61
15.2 0.33
83.2 0.14
71.2 0.11
82.5 0.22
27.8 0.14
-
108.8 0.43
89.3 0.12
108.7 0.38
98.9 0.29
95.5 0.43
100.3 0.28
99.6 0.32
102.4 0.32
88.7 0.25
-
7
8
9
10
11
12
13
14
15
16
80.5 0.24
107.9 0.32
23.8 0.35
33.6 0.12
106.7 0.42
0.8 0.08
77.1 0.72
103.2 0.38
20.5 0.28
31.2 0.25
104.2 0.34
0.7 0.07
100.8 0.43
187.8 0.31
85.7 0.56
96.7 0.43
167.8 0.81
12.3 0.12
17
18
19
20
Doxorubicin
– Not active
A549- Human lung carcinoma cell line
MCF7- Human breast carcinoma cell line
IMR90- Normal human lung cell line
<80 μM against cancer cell lines. Compounds 5 and 15
fail to preserve the cytotoxic activity against all the cancer
cell lines. Compounds 2, 4, 17, and 20 were least active
against both the cancer cell lines but their toxicity is also
less against IMR90.
The cytotoxicity of compounds against human normal
lung cell line (IMR90) showed that all the compounds in
the series were 7–16 times less toxic as compared with
the reference drug doxorubicin, except compound 5 and
15 which did not provoke any toxicity (Figure 3).
From the data of compounds (1–20), it was concluded
that the Schiff base ligand H2L3 (3) was found to be more
active and its diorganotin (IV) complexes (9–12) was also
found active against all the cancer cell line but its ethyl
complex was most active and its methyl complex was
least active. The ethyl complex of ligand 2 and 4 was also
found to be more potent than the other complexes of that
group against all the cancer cell lines. The trend of the
cytotoxic activity of diorganotin (IV) complexes (5–20) is
Et > Bu > Ph > Me.
The SAR of (1–20) compounds is studied to found
out the effect of substituents on the biological activity.
All the synthesized compounds (1–20) were found to be
active against both the cancer cell lines (except com-
pound 5 and 15), and compound 3 (H2L3) and 10
(Et2SnL2) were particularly more active against both the
cancer cell lines. In compound 3 (H2L3), the benzene
ring is substituted with diethylamino group at meta posi-
tion with respect to hydroxyl group. The complexation
of this ligand (3) with dibutyltin resulted in complete
loss of anticancer activity (15) but complexation with
methyl groups (13) and phenyl (16) groups resulted in
about five-fold decrease in anticancer activity as com-
pared to ligands. Although, its diethyl complex (14)
resulted in decrease in anticancer activity, but still the
activity was significantly good.

DEVI ET AL.
15 of 17
FIGURE 4 Cytotoxicities of synthesized compounds (1–20) against (a) Human lung carcinoma cell line (A549), (b) Human breast
carcinoma cell line (MCF7), (c) Normal human lung cell line (IMR90)
Compound 10 having very good activity against both
A549 and MCF7 cell lines is a coordination compound of
ligand 2 (H2L2). Although, compound 2 (having nitro
substitution on benzene ring) itself is very poorly active,
but on complexation the activity is increased and diethyl
complex (10) is 12–15 times more potent (one of the most
active compound in the series). On the other hand, the
complexation of ligand 2 with tin having methyl groups
(9), butyl groups (11) and phenyl groups (12) resulted in
almost two-fold enhancement of anticancer activity as
compared to compound 2 itself.
methyl complex (5) resulted in complete abolishment of
anticancer activity. However, the ethyl (6), butyl (7) and
phenyl (8) complexes somewhat weakens the anticancer
activity of ligand itself.
Ligand 4 having two bromo substitutions on the ben-
zene ring was poorly active, but its complexation with
ethyl (18) resulted in almost five times enhancement of
anticancer activity. Similarly, its butyl complex (19)
resulted in around three times enhancement of antican-
cer activity and methyl (17) and phenyl complex (20) has
no effect on its anticancer activity.
In case of compound 1, where no substitution on the
benzene ring, the anticancer activity is moderate, but its
The literature survey suggests that probable target for
cytotoxic activity is DNA. The organotin (IV) complexes

16 of 17
DEVI ET AL.
attacks on the primary structure of DNA, induce long-
lasting effects and gives variable response in cells which
leads to cell death due to apoptosis or necrosis. Further,
the complexes induce cytotoxicity through inhibition of
macromolecules synthesis, decrease DNA synthesis and
interaction with cells which increase cytosolic calcium
ion concentration. Diorganotin (IV) dichloride induce the
apoptosis by increase in concentration of calcium ions
which results in release of cytochrome-c and activation of
caspases leads to DNA fragmentation.[66–70] Hence, it is
anticipated that diorganotin complexes of hydrazide
Schiff bases exert the cytotoxic effects by involving above
discussed pathways.
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One of the authors Dr. Jai Devi acknowledges Depart-
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for financial support. The author Ms. Jyoti Yadav (SRF)
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ORCID
Jai Devi https://orcid.org/0000-0003-0434-3193

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How to cite this article: Devi J, Yadav J,
Kumar D, Jindal DK, Basu B. Synthesis, spectral
analysis and in vitro cytotoxicity of diorganotin
(IV) complexes derived from indole-3-butyric
hydrazide. Appl Organomet Chem. 2020;e5815.
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