Synthesis of 1-(4-((E)-3-arylacryloyl) phenyl)-3,4-dibromo-1Hpyrrole-2,5- diones and screening for anti-Candida and antituberculosis activity

Article abstract of DOI:10.1007/s00044-011-9718-x

A series of eleven 1-(4-((E)-3-arylacryloyl) phenyl)-3,4 dibromo-1H-pyrrole-2,5-diones (4′-aminochalcone- based dibromomaleimides) were synthesized using maleic anhydride and p-aminoacetophenone as starting material. Furthermore, there has been some additional work investigating the effect of these derivatives on biological activity. They were characterized using FTIR, ¹H NMR, ¹³C NMR, ESI mass spectroscopy, and elemental analysis. The compounds show anti-Candida & antituberculosis activity.

Full text of DOI:10.1007/s00044-011-9718-x

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:1977–1983
DOI 10.1007/s00044-011-9718-x
ORIGINAL RESEARCH
Synthesis of 1-(4-((E)-3-arylacryloyl) phenyl)-3,4-dibromo-1H-
pyrrole-2,5-diones and screening for anti-Candida
and antituberculosis activity
•
J. R. Patel B. Z. Dholakiya
Received: 11 May 2011 / Accepted: 18 June 2011 / Published online: 9 July 2011
Ó Springer Science+Business Media, LLC 2011
Abstract A series of eleven 1-(4-((E)-3-arylacryloyl)
phenyl)-3,4 dibromo-1H-pyrrole-2,5-diones (40-aminoch-
alcone-based dibromomaleimides) were synthesized using
maleic anhydride and p-aminoacetophenone as starting
material. Furthermore, there has been some additional
work investigating the effect of these derivatives on bio-
maleanilic acid precursor and reported cytostatic activities
against human Molt 4/C8 and CEM T-lymphocytes and
murine L1210 cell lines.
Recently, several structurally interesting compounds
with substituted maleic anhydride and maleimide moieties
have been isolated as bioactive compounds. As continua-
tion to our research, we aim to synthesize new compounds
and evaluate against multidrug resistance tuberculosis.
Previously, Dholakiya et al. have synthesized a series of
40-aminochalcone-based dibromomaleimide derivatives
(Patel and Dholakiya, 2011). However, no information is
available on their antituberculosis properties. Hence, in this
article, we report antituberculosis properties of some new
synthesized 40-aminochalcone-based dibromomaleimide.
1
logical activity. They were characterized using FTIR, H
NMR, 13C NMR, ESI mass spectroscopy, and elemental
analysis. The compounds show anti-Candida & antituber-
culosis activity.
Keywords 1-(4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-diones ꢀ Anti-Candida ꢀ
Antituberculosis
Introduction
Experimental
Mycobacterium tuberculosis is the most deadly bacterial
pathogen and is responsible for nearly 3 million deaths
every year. Therefore, we took interest in synthesizing
compounds having activity against resistant pathogen
(Ortega et al., 1999; Kasimogullari and Cesur, 2004;
Nielsen et al., 2004; Guzel et al., 2006; Aridoss et al.,
2008; Castagnolo et al., 2008; Judge et al., 2011; Rani
et al., 2011). Jha et al. (2007) have synthesized a series of
40-aminochalcone-based maleimides from 40-acetyl-N-
Materials and instrumentation
All reagents were of analytical reagent grade and were used
without further purification. Solvents employed were
purified by standard procedure before to use. Maleic
anhydride and p-aminoacetophenone was purchased from
Aldrich, and bromine was purchased from Merck (Perrin
and Armarego, 1988). The melting points were determined
in open capillary on Veego (Model: VMP-D) electronic
apparatus and are uncorrected. To monitor the reactions, as
well as, to establish the identity and purity of reactants and
products, thin layer chromatography was performed on
microscopic glass slides (2 9 7.5 cm) coated with silica
gel-G, using toluene–acetone and chloroform–methanol, as
the solvent systems, and spots were visualized under UV
radiation. Elemental analysis was performed using a
PerkinElmer, USA 2400-II CHN analyser. FTIR spectra
J. R. Patel ꢀ B. Z. Dholakiya (&)
Department of Applied Chemistry, S.V. National Institute
of Technology, Ichchhanath, Surat 395007, Gujarat, India
e-mail: bharat281173@gmail.com
J. R. Patel
e-mail: pateljigar.svnit@gmail.com
123

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Med Chem Res (2012) 21:1977–1983
(4000–400 cm-1) recorded on Simadzu 8400-S spectro-
photometer using KBr disk. Nuclear magnetic resonance
spectra were recorded on Varian 400 MHz model spec-
trometer using DMSO and or DMF as a solvent and TMS
as internal reference (Chemical shifts in d ppm). The ESI
mass spectrum of compounds was recorded at Oxygen
Healthcare Research Lab, Ahmedabad.
dibromomaleimide and various aryl aldehydes under basic
conditions afforded the 40-aminochalcone-based dibromo-
maleimides (Dimmock et al., 2003; Bag et al., 2009; Lee
et al., 2009; Patil et al., 2009). New compounds were
completely characterized based on their spectroscopy data.
Derivatives are shown in Table 1.
1-(4-((E)-3-arylacryloyl) phenyl)-3,4 dibromo-1H-
Synthesis of 40-amino maleimides 3
pyrrole-2,5-dione 5a
1
Mixture of maleic anhydride (1) and p-amino acetophe-
none (2) (1:1.1) in diethyl ether catalysed by DABCO (1,4-
diazabicyclo [2.2.2] octane) (0.5 mol) in short reaction
time, and high yield was performed to give 40-amino
maleimide (Scheme 1) (Beheshtia et al., 2010).
Yield 67%; m.p. 152°C; H NMR (500 MHz, DMF), 3.52
d & 8.23 d ppm (DMF solvent), 7.45 d ppm (1H, d,
J = 15.5 Hz, E- vinylic-H), 7.66 d ppm (2H, dd, Ar–H),
6.43–7.42 (5H, m, Ar–H), 7.75 d ppm (1H, d, J = 15.5 Hz,
E- vinylic-H); 13C NMR (500 MHz, DMF) 40.1 (C-3,4), 77
(C-8), 118 (C-7), 124 (C-400), 126.9 (C-200, 600), 127.85 (C-
3, 500), 129 (C-100), 130.22 (C-20, 60), 131.01(C-30, 50), 138
(C-10), 167.78 (C-2,5), 171 (C-6) d ppm; FTIR (KBr) tmax
cm-1: 3028 (C=C), 1716 (C=O), 1527 (C=C of Ar), 835 (p-
disubstituted Ar), 655 (C–Br); ESIMS m/z 462 (M ? 1)
Anal. Calcd for CHNOBr: C, 49.49; H, 2.40; N, 3.04.
Found: C, 49.44; H, 2.38; N, 2.99.
Synthesis of 40-amino 3,4 dibromomaleimides 4
A solution of 40-amino maleimide (1500 mg, 1 mol), alu-
minium chloride (28 mg, 0.02 mol), and bromine (1.5 ml,
2 mol), was heated at 120°C during 16 h in a sealed teflon
tube. After cooling the tube to room temperature, the mixture
was taken up in ethyl acetate, filtered, and the filtrate was
concentrated in vacuo to afford the title compound
(3610 mg, 94%), as a yellow solid, mp 129°C (Dubernet
et al., 2005; Stewart et al., 2007; Cheng et al., 2008).
1-(30,40-Dimethoxy-4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-dione 5b
1
Yield 57%; m.p. 116–118°C; H NMR (500 MHz, DMF)
Preparation of chalcone from dibromomaleimides 5a–k
2.9 d ppm (3H, s, –OCH3), 3.04 d ppm (3H, s, –OCH3),
3.55 d & 8.063 d ppm (DMF solvent), 7.56 d ppm (1H, d,
J = 15.3 Hz, E- vinylic-H), 6.78–7.68 d ppm (2H, dd, Ar–
H), 7.81 d ppm (1H, d, J = 15.3 Hz, E- vinylic-H),
The target compounds were prepared as shown in
Scheme 1. Claisen–Schmidt condensation of 40-acetyl 3,4-
Scheme 1 Synthesis of compounds 5a–k from maleic anhydride 1 and p-aminoacetophenone 2
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Med Chem Res (2012) 21:1977–1983
1979
Table 1 List of compounds with their structures and different groups
Structure of Compounds with different groups
Structure of Compounds with different groups
5a (R1, R2 & R3 = H)
5g (R1 & R2= H, R3=CH3)
5b (R1 = H, R2 & R3 = OCH3)
5h (R1 & R2= H, R3=OCH3)
5c (R1= H, R2= -NO2 & R3=OCH3)
5i (R1 & R2= H, R3 = OH)
5j (R1& R3= H, R2= -NO2)
5k (R1= H & R2& R3 = Cl)
5d (R1= OH, R2& R3 =H)
5e (R1 & R2= H, R3 = Cl)
5f (R1= Cl & R2& R3 =H)
6.38–8.37 d ppm (3H, m, Ar–H); 13C NMR (500 MHz,
DMF) 41.21 (C-3,4), 58.2 (OCH3 of C-500), 62.3 (OCH3 of
C-400), 76.44 (C-8), 118 (C-7), 124 (C-200), 129 (C-600),
129.8 (C-300), 131.01 (C-30, 50), 131.1 (C-100), 132 (C-500),
137.6 (C-20, 60), 139.9 (C-10), 144 (C-400), 167.8 (C-2,5),
171.9 (C-6) d ppm; FTIR (KBr) tmax cm-1: 3000 (C=C),
1580 (C=O), 1520 (C=C of Ar), 835 (p-disubstituted Ar),
650 (C–Br); ESIMS m/z 523 (M ? 2). Anal. Calcd for
CHNOBr: C, 48.40; H, 2.90; N, 2.69. Found: C, 48.39; H,
2.99; N, 2.64.
1-(30-Nitro, 40-methoxy-4-((E)-3-arylacryloyl) phenyl)-
3,4 dibromo-1H-pyrrole-2,5-dione 5c
1
Yield 76%; m.p. 116–118°C; H NMR (500 MHz, DMF)
3.0 d ppm (3H, s, –OCH3), 3.53 d & 8.12 d ppm (DMF
solvent), 7.44 d ppm (1H, d, J = 15.4 Hz, E- vinylic-H),
6.78–7.68 d ppm (2H, dd, Ar–H), 7.78 d ppm (1H, d,
J = 15.4 Hz, E- vinylic-H) 6.55–8.45 d ppm (3H, m, Ar–
H); 13C NMR (500 MHz, DMF) 39.91 (C-3,4), 57.22
(OCH3 of C-500), 76 (C-8), 118 (C-7), 124 (C-300), 127
123

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Med Chem Res (2012) 21:1977–1983
(C-100), 129 (C-200, 600), 130 (C-30, 50), 131 (C-20, 60), 138
(C-10), 140 (C-40), 143 (C-400), 148 (C-500), 168 (C-2,5), 172
(C-6) d ppm; FTIR (KBr) tmax cm-1: 2990 (C=C), 1589
(C=O), 1510 (C=C of Ar), 1250 (C–O), 840 (p-disubsti-
tuted Ar), 653 (C–Br); ESIMS m/z 537 (M ? 1) Anal.
Calcd for CHNOBr: C, 44.81; H, 2.26; N, 5.23. Found: C,
44.79; H, 2.23; N, 5.25.
133(C-100), 137 (C-600), 138 (C-10), 140 (C-40, 400), 167 (C-
2,5), 171.1 (C-6) d ppm; FTIR (KBr) tmax cm-1: 3022
(C=C), 1578 (C=O), 1527 (C=C of Ar), 836 (p-disubsti-
tuted Ar), 700 (C–Cl), 654 (C–Br); ESIMS m/z 493
(M ? 1) Anal. Calcd for CHNOBr: C, 47.85; H, 2.29; N,
2.93. Found: C, 47.87; H, 2.31; N, 2.97.
1-(40-Methyl-4-((E)-3-arylacryloyl) phenyl)-3,4
1-(20-Hydroxyl-4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-dione 5g
dibromo-1H-pyrrole-2,5-dione 5d
Yield 76%; m.p. 169°C; 1H NMR (500 MHz, DMF) 3.37 d
ppm (3H, s, –CH3) 3.54 d & 8.02 d ppm (DMF solvent),
7.67 d ppm (1H, d, J = 15.2 Hz, E- vinylic-H), 6.76–7.68
d ppm (2H, dd, Ar–H), 7.77 d ppm (1H, d, J = 15.2 Hz, E-
vinylic-H), 6.51–8.43 d ppm (4H, m, Ar–H); 13C NMR
(500 MHz, DMF) 40.12 (C-3,4), 57.21 (–CH3 of C-400),
72.44 (C-8), 118.3 (C-7), 123.2 (C-20, 60), 128.1 (C-200, 600),
129 (C-300), 129.2 (C-30, 50), 131.1 (C-100), 133 (C-300, 500),
137.2 (C-400), 138 (C-10), 140.1 (C-40), 162.8 (C-2,5), 171
(C-6) d ppm; FTIR (KBr) tmax cm-1: 3030 (C=C), 1582
(C=O), 1529 (C=C of Ar), 839 (p-disubstituted Ar), 657
(C–Br); ESIMS m/z 476 (M ? 1) Anal. Calcd for
CHNOBr: C, 50.56; H, 2.76; N, 2.95. Found: C, 50.53; H,
2.78; N, 2.93.
Yield 43%; m.p. 36–38°C; 1H NMR (500 MHz, DMF)
3.34 d ppm (1H, s, –OH), 3.50 d & 8.1 d ppm (DMF
solvent), 7.56 d ppm (1H, d, J = 15.2 Hz, E- vinylic-H)
6.73–7.74 d ppm (2H, dd, Ar–H), 7.77 d ppm (1H, d,
J = 15.2 Hz, E- vinylic-H) 6.45–8.2 d ppm (4H, m, Ar–H),
13C NMR (500 MHz, DMF) 40.91 (C-3,4), 75.77 (C-8),
118 (C-7), 127 (C-20, 60), 128 (C-300), 131 (C-100), 127 (C-
200), 129 (C-400), 129.4 (C-30, 50), 130 (C-500), 138 (C-10),
140.2 (C-40), 142 (C-600), 168 (C-2,5), 170.98 (C-6) d ppm;
FTIR (KBr) tmax cm-1: 3350 (–OH), 3084 (C=C), 1597
(C=O), 1525 (C=C of Ar), 1410 (NO2), 1230 (C–O), 840
(p-disubstituted Ar), 537 (C–Br); ESIMS m/z 477 (M?)
Anal. Calcd for CHNOBr: C, 47.83; H, 2.32; N, 2.92.
Found: C, 47.85; H, 2.29; N, 2.96.
1-(40-Methoxy-4-((E)-3-arylacryloyl) phenyl)-3,4
1-(40-Chloro-4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-dione 5h
dibromo-1H-pyrrole-2,5-dione 5e
1
Yield 62%; m.p. 157–158°C; H NMR (500 MHz, DMF)
1
Yield 78%; m.p. 162–163°C; H NMR (500 MHz, DMF)
3.01 d ppm (3H, s, –OCH3), 3.53 d & 8.13 d ppm (DMF
solvent), 7.68 d ppm (1H, d, J = 15.5 Hz, E- vinylic-H),
6.72–7.63 d ppm (2H, dd, Ar–H), 7.76 d ppm (1H, d,
J = 15.5 Hz, E- vinylic-H) 6.39–8.39 d ppm (3H, m, Ar–
H); 13C NMR (500 MHz, DMF) 41.2 (C-3,4), 58.21
(–OCH3 of C-400), 76.43 (C-8), 119 (C-7), 125 (C-20, 60),
129 (C-200, 600), 129.1 (C-300), 129.9 (C-30, 50), 131.2 (C-100),
133 (C-300, 500), 137.6 (C-400), 140 (C-10), 143 (C-40), 167.9
(C-2,5), 173 (C-6) d ppm; FTIR (KBr) tmax cm-1: 3000
(C=C), 1580 (C=O), 1520 (C=C of Ar), 835 (p-disubsti-
tuted Ar), 650 (C–Br); ESIMS m/z 492 (M ? 1) Anal.
Calcd for CHNOBr: C, 48.91; H, 2.67; N, 2.85. Found: C,
48.89; H, 2.64; N, 2.83.
3.55 d & 8.063 d ppm (DMF solvent), 7.6 d ppm (1H, d,
J = 15.3 Hz, E- vinylic-H), 6.78–7.68 d ppm (2H, dd, Ar–
H), 7.78 d ppm (1H, d, J = 15.3 Hz, E- vinylic-H),
6.55–8.45 d ppm (4H, m, Ar–H); 13C NMR (500 MHz,
DMF) 39.91 (C-3,4), 75.23 (C-8), 118 (C-7), 124 (C-20, 60),
127 (C-200, 600), 129 (C-300), 129.4 (C-30, 50), 130 (C-100, 300,
500), 140 (C-400), 138 (C-10), 140 (C-40), 166.78 (C-2,5),
171.22 (C-6) d ppm; FTIR (KBr) tmax cm-1: 3020 (C=C),
1585 (C=O), 1525 (C=C of Ar), 835 (p-disubstituted Ar),
697 (C–Cl), 538 (C–Br); ESIMS m/z 492 (M?) Anal.
Calcd for CHNOBr: C, 47.83; H, 2.32; N, 2.92. Found: C,
47.85; H, 2.29; N, 2.96.
1-(20-Chloro-4-((E)-3-arylacryloyl) phenyl)-3,4
1-(40-Hydroxyl-4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-dione 5f
dibromo-1H-pyrrole-2,5-dione 5i
1
Yield 73%; m.p. 166–168°C; H NMR (500 MHz, DMF)
Yield 48%; m.p. 41–43°C; 1H NMR (500 MHz, DMF)
3.34 d ppm (1H, s, –OH), 3.52 d & 8.12 d ppm (DMF
solvent), 7.56 d ppm (1H, d, J = 15.2 Hz, E- vinylic-H)
6.73–7.74 d ppm (2H, dd, Ar–H), 7.77 d ppm (1H, d,
J = 15.2 Hz, E- vinylic-H) 6.45–8.2 d ppm (4H, m, Ar–H),
13C NMR (500 MHz, DMF) 41 (C-3,4), 75.7 (C-8), 116
(C-7), 126 (C-300), 127 (C-20, 60), 131 (C-100), 127 (C-200),
3.53 d & 8.063 d ppm (DMF solvent), 7.54 d ppm (1H, d,
J = 15.5 Hz, E- vinylic-H), 6.77–7.66 d ppm (2H, dd, Ar–
H), 7.82 d ppm (1H, d, J = 15.5 Hz, E- vinylic-H),
6.53–8.44 d ppm (4H, m, Ar–H); 13C NMR (500 MHz,
DMF) 40.01 (C-3,4), 75.23 (C-8), 118.5 (C-7), 123 (C-20,
60), 128 (C-200), 129 (C-300), 129.4 (C-30, 50), 131 (C-300, 500),
123

Med Chem Res (2012) 21:1977–1983
1981
129 (C-600), 129.4 (C-30, 50), 130 (C-500), 138 (C-10), 139
(C-40), 142 (C-400), 167 (C-2,5), 168.9 (C-6) d ppm; FTIR
(KBr) tmax cm-1: 3350 (–OH), 3084 (C=C), 1597 (C=O),
1525 (C=C of Ar), 1230 (C–O), 840 (p-disubstituted Ar),
537 (C–Br); ESIMS m/z 477 (M?) Anal. Calcd for
CHNOBr: C, 47.83; H, 2.32; N, 2.92. Found: C, 47.80; H,
2.31; N, 2.94.
Alamar Blue Assay (MABA) as described earlier. DMSO
was used as a solvent to dissolve the test compound. The
minimal inhibitory concentration (MIC) was defined as the
lowest concentration to effect a 90% inhibition of growth
compared with drug-free controls (Rattan, 2000).
Results and discussion
1-(30-Nitro-4-((E)-3-arylacryloyl) phenyl)-3,4 dibromo-
1H-pyrrole-2,5-dione 5j
The important infrared spectral bands and their tentative
assignments for dibromocompounds and its chalcones were
Yield 71%; m.p. 146°C; 1H NMR (500 MHz, DMF) 3.53 d
& 8.12 d ppm (DMF solvent), 7.44 d ppm (1H, d,
J = 15.4 Hz, E- vinylic-H), 6.78–7.68 d ppm (2H, dd, Ar–
H), 7.78 d ppm (1H, d, J = 15.4 Hz, E- vinylic-H)
6.55–8.45 d ppm (3H, m, Ar–H); 13C NMR (500 MHz,
DMF) 38.9 (C-3,4), 74 (C-8), 117.9 (C-7), 124 (C-300),128
(C-100), 129 (C-200, 600), 129.9 (C-30, 50), 131 (C-20, 60), 138
(C-10), 141 (C-40), 143 (C-400), 146 (C-500), 169 (C-2,5), 171
(C-6) d ppm; FTIR (KBr) tmax cm-1: 2990 (C=C), 1589
(C=O), 1510 (C=C of Ar), 1410 (NO2), 1250 (C–O), 840
(p-disubstituted Ar), 653 (C–Br); ESIMS m/z 507 (M ? 1)
Anal. Calcd for CHNOBr: C, 45.09; H, 1.99; N, 5.54.
Found: C, 44.99; H, 2.01; N, 5.54.
1
recorded as KBr disks and are presented. The H NMR
spectra revealed signals 3.53 dppm appear as a singlet for
six protons of two methyl groups & 8.12 d ppm appear as
singlet for one proton of formyl group in DMF solvent. The
1H NMR data of compounds revealed signals between 6.78
and 8.50 d ppm for aromatic protons of substituted phenyl
ring. The IR spectra of compounds 5a–h revealed a char-
acteristic bands between 3020 and 3090 cm-1 confirming
the presence of (C=C) groups. The 1H NMR data of
compounds revealed signals between 7.48 and 7.53 d ppm
and between 7.74 and 7.80 d ppm for asymmetric aliphatic
(C=C) of Chalcones. IR spectrum of the compounds
showed
a characteristic bands between 1580 and
1716 cm-1 confirming the presence of C=O groups and
C–Br present between 537 and 655 cm-1 of dibromoma-
leimides. 13C NMR spectra of compounds showed char-
acteristic peak around 40.1, 77, 118, 124, 126.9, 127.85,
129, 130.22, 131.01, 138, 167.78, and 171 d ppm. IR
spectrum of the compound 5c showed a characteristic band
1-(20,40-Dichloro-4-((E)-3-arylacryloyl) phenyl)-3,4
dibromo-1H-pyrrole-2,5-dione 5k
Yield 79%; m.p. 158°C; 1H NMR (500 MHz, DMF) 3.55 d
& 8.063 d ppm (DMF solvent), 7.6 d ppm (1H, d,
J = 15.3 Hz, E- vinylic-H), 6.78–7.68 d ppm (2H, dd, Ar–
H), 7.78 d ppm (1H, d, J = 15.3 Hz, E- vinylic-H),
6.55–8.45 d ppm (3H, m, Ar–H); 13C NMR (500 MHz,
DMF) 40 (C-3,4), 77 (C-8), 118 (C-7), 123 (C-20, 60), 128
(C-200), 129 (C-300), 130 (C-30, 50), 130 (C-100, 300, 500), 138
(C-10), 141 (C-400, 600), 142 (C-40), 165 (C-2,5), 170 (C-6) d
ppm; FTIR (KBr) tmax cm-1: 3020 (C=C), 1585 (C=O),
1525 (C=C of Ar), 835 (p-disubstituted Ar), 697 (C–Cl),
538 (C–Br); ESIMS m/z 530 (M?) Anal. Calcd for
CHNOBr: C, 43.06; H, 1.71; N, 2.64. Found: C, 42.93; H,
1.69; N, 2.65.
at 1410 cm-1 confirming the presence of –NO2 group. 13
C
NMR spectra of compound 5c showed characteristic peak
around 39.91, 57.22, 76, 118, 124, 129, 130, 131, 138, 140,
143, 148, 168, and 172 d ppm (Silverstein and Webster,
1997) (Fig. 1).
Anti-Candida activity
The anti-Candida activity of compounds was studies with
C. albicans (Table 2). Nystatin and Greseofulvin were used
as references for inhibitory activity against C. albicans. All
compounds showed quite good anti-Candida activity. The
Anti-Candida studies
All the synthesized compounds were tested for their anti-
Candida activity (MIC) in vitro by the dilution method with
C. albicans taking Nystatin and Greseofulvin as standard
drugs (Rattan, 2000).
Antituberculosis studies
All the synthesized compounds were tested for inhibition
of M. tuberculosis H37 RV ATCC 27294 using Microplate
Fig. 1 Numbering of structures 5a–k
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Med Chem Res (2012) 21:1977–1983
Table 2 Anti-Candida activity of the compounds
Table 3 Antituberculosis activity of the compounds
Compounds
Minimal inhibitory
Compounds
Minimal inhibitory concentration,
MIC (lg/ml)
M. tuberculosis (H37RV)
concentration, MIC (lg/ml)
C. albicans
MTCC227
MTCC 200
5a
250
500
5a
500
500
1000
50
5b
5b
5c
1000
100
5c
5d
5d
5e
250
5e
100
250
500
500
60
5f
1000
1000
1000
150
5f
5g
5g
5h
5h
5i
5i
5j
250
5j
200
500
5k
500
5k
Standard drugs
Nystatin
Standard drugs
Refampicin
Isoniazid
100
500
40
Greseofulvin
0.2
Bold values indicate comparative with standard drugs values
Bold values indicate comparative with standard drugs values
Fig. 3 Comparative analysis for antituberculosis activity of synthe-
sized compounds and standard drugs
Fig. 2 Comparative analysis for anti-Candida activity of synthesized
compounds and standard drugs
Conclusion
The present investigation revealed 40-aminochalcone-based
dibromomaleimides as potential leads for development of
new drugs. We can also conclude from the result of anti-
Candida activity of compounds 5b and 5d comparable with
the standard drugs Greseofulvin and Nystatin, respectively,
in the case of C. albicans. Comparative analysis showed
moderate antimycobacterial activity of 5d as compared
with the standard drug Rifampicin.
compounds 5b and 5d were comparable active with Gre-
seofulvin and Nystatin, respectively (Fig. 2).
Antituberculosis studies
The final compounds were tested for in vitro antitubercu-
losis activity against M. tuberculosis. Streptomycin, Iso-
niazid, Rifampicin, and Ethambutol were used as standard
in this test. Primary antituberculosis activity screening
results of these compounds can be seen in Table 3. The
compound 5d is comparable with the standard drug Rif-
ampicin, while other compounds show comparatively
lower active than other standards (Fig. 3).
Acknowledgments The author wish to thank the Department of
Applied Chemistry, SVNIT, Surat, for providing laboratory facilities
and D. P. Rajani, Microcare Laboratory, Surat, for antimicrobial
activity determinations. Analytical facilities providing by the Centre
of Excellence, Vapi, Oxygen Healthcare Research Lab, Ahmedabad,
123

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