Derivatives for use against M. tuberculosis H37Rv and MDR-TB strain
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1-(4-Methylbenzylidene)-4-(1-((4-methyl piperazine-1-yl)
methyl)-2,3-dioxoindolin-5-yl)semicarbazide (7l) FT-IR
(KBr): cm-1 3054 (Ar C–HStr); 1728 (C=O, isatin); 1522
1-(4-Chlorobenzylidene)-4-(2,3-dioxo-1-((4-(3-(trifluoro-
methyl) phenyl) piperazin-1-yl) methyl)indolin-5-yl)semi-
carbazide (7p) FT-IR (KBr): cm-1 2986 (Ar C–HStr);
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(CH=N); H-NMR (300 MHz, DMSO-d6, d ppm): 2.20 (s,
1744 (C=O, isatin); 1572 (CH=N); 745 (C–Cl); H-NMR
3H, CH3); 2.42 (s, 3H, N–CH3); 2.5–2.80 (m, 8H, pipera-
zine); 4.55 (s, 2H, –CH2); 7.02-7.88 (m, 7H, Ar–CH); 8.28
(s, 1H, Ar–NH); 8.54 (s, 1H, CH=N); 9.90 (s, 1H, CONH);
MS (EI) m/z: 434 [M?]; Anal. Calcd for C23H26N6O3: C,
63.58; H, 6.03; N, 19.34. Found: C, 63.72; H, 6.05; N,
19.41.
(300 MHz, DMSO-d6, d ppm): 2.52–2.78 (m, 8H, pipera-
zine); 4.42 (s, 2H, –CH2); 6.66–7.84 (m, 11H, Ar–CH);
8.24 (s, 1H, Ar–NH); 8.52 (s, 1H, CH=N); 9.92 (s, 1H,
CONH); MS (EI) m/z: 587 [M?2]; Anal. Calcd for
C28H24ClF3N6O3: C, 57.49; H, 4.14; N, 14.37. Found: C,
57.70; H, 4.16; N, 14.42.
1-(4-Chlorobenzylidene)-4-(2,3-dioxo-1-((4-phenyl pipera-
zin-1-yl)methyl)indolin-5-yl)semicarbazide (7m) FT-IR
(KBr): cm-1 2984 (Ar C–HStr); 1732 (C=O, isatin); 1560
1-(4-Nitrobenzylidene)-4-(2,3-dioxo-1-((4-(3-(trifluoromethyl
phenyl)piperazin-1-yl) methyl)indolin-5-yl)semicarbazide
(7q) FT-IR (KBr): cm-1 3036 (Ar C–HStr); 1750 (C=O,
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(CH=N); 774 (C–Cl); H-NMR (300 MHz, DMSO-d6, d
isatin); 1534 (CH=N); 1562 & 1344 (C-NO2); H-NMR
ppm): 2.58–2.94 (m, 8H, piperazine); 4.62 (s, 2H, –CH2);
6.78–7.98 (m, 12H, Ar–CH); 8.12 (s, 1H, Ar–NH); 8.46 (s,
1H, CH=N); 9.94 (s, 1H, CONH); 13C-NMR (100 MHz,
DMSO-d6, d ppm): 72.6 (2C), 58.6 (2C) (Piperazinyl); 74.4
(CH2); 112.6, 122.9, 130.4 (CH, Indolyl); 116.3 (2C),
120.4, 125.8 (2C), 127.4 (2C), 128.2 (2C) (CHarom); 131.4,
133.6, 136.2 (C, Indolyl); 132.5, 139.1, 142.6 (Carom);
144.3 (C=N); 162.9 (C=O, Urea); 176.8, 181.8 (C=O,
Indolyl). MS (EI) m/z: 519 [M?2]; Anal. Calcd for
C27H25ClN6O3: C, 62.73; H, 4.87; N, 16.26. Found: C,
62.92; H, 4.89; N, 16.32.
(300 MHz, DMSO-d6, d ppm): 2.84–3.06 (m, 8H, pipera-
zine); 4.32 (s, 2H, –CH2); 6.72–7.92 (m, 11H, Ar–CH); 8.36
(s, 1H, Ar–NH); 8.58 (s, 1H, CH=N); 9.91 (s, 1H, CONH);
13C-NMR (100 MHz, DMSO-d6, d ppm): 70.2 (2C), 62.4
(2C) (Piperazinyl); 72.4 (CH2); 113.6, 123.8, 129.6 (CH,
Indolyl); 120.3 (CF3); 116.2, 118.9, 122.6, 125.6, 126.8 (2C),
127.9 (2C), (CHarom); 130.2, 133.4, 136.2 (C, Indolyl);
131.8, 138.6, 140.8, 144.6 (Carom); 143.9 (C=N); 162.4
(C=O, Urea); 174.2, 182.3 (C=O, Indolyl). MS (EI) m/z: 595
[M?]; Anal. Calcd for C28H24F3N7O5: C, 56.47; H, 4.06; N,
16.46. Found: C, 56.66; H, 4.07; N, 16.50.
1-(4-Methylbenzylidene)-4-(2,3-dioxo-1-((4-(3-(trifluoromethyl)
phenyl)piperazin-1-yl) methyl)indolin-5-yl)semicarbazide (7r)
FT-IR (KBr): cm-1 2998 (Ar C–HStr); 1734 (C=O, isatin);
1530 (CH=N); 1H-NMR (300 MHz, DMSO-d6, d ppm): 2.34
(s, 3H, CH3); 2.72–2.98 (m, 8H, piperazine); 4.36 (s, 2H,
–CH2); 6.70-7.84 (m, 11H, Ar–CH); 8.22 (s, 1H, Ar–NH);
8.48 (s, 1H, CH=N); 9.88 (s, 1H, CONH); MS (EI) m/z: 564
[M?]; Anal. Calcd for C29H27F3N6O3: C, 61.70; H, 4.82; N,
14.89. Found: C, 61.92; H, 4.81; N, 14.95.
1-(4-Nitrobenzylidene)-4-(2,3-dioxo-1-((4-phenyl piperazin-1-
yl)methyl)indolin-5-yl)semicarbazide (7n) FT-IR (KBr):
cm-1 3030 (Ar C–HStr); 1738 (C=O, isatin); 1492 (CH=N);
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1538 & 1374 (C-NO2); H-NMR (300 MHz, DMSO-d6, d
ppm): 2.58–2.84 (m, 8H, piperazine); 4.50 (s, 2H, –CH2);
6.66–7.88 (m, 12H, Ar–CH); 8.26 (s, 1H, Ar–NH); 8.62 (s,
1H, CH=N); 9.92 (s, 1H, CONH); MS (EI) m/z: 527 [M?];
Anal. Calcd for C27H25N7O5: C, 61.47; H, 4.78; N, 18.59.
Found: C, 61.68; H, 4.80; N, 18.66.
Evaluation of antimycobacterial activity
1-(4-Methylbenzylidene)-4-(2,3-dioxo-1-((4-phenyl pipera-
zin-1-yl)methyl)indolin-5-yl)semicarbazide (7o) FT-IR
(KBr): cm-1 3042 (Ar C–HStr); 1740 (C=O, isatin); 1510
The target compounds were screened for their in vitro
antimycobacterial activity against M. tuberculosis H37Rv
(ATCC 27294) and MDR-TB by resazurin assay method
(Taneja et al. 2007) and their MIC values were determined.
Resazurin reduction assays were developed to screen for
drugs and compounds active against growing and dormant
mycobacteria. The MDR-TB strain was obtained from
Tuberculosis Research Center, Chennai, India, and was
resistant to rifampicin, isoniazid, ethambutol and ofloxacin.
M. tuberculosis strains were developed in Middlebrook
7H9 broth supplemented with 10 % albumin dextrose
complex, 0.05 % tween 80 and 0.05 % glycerol. The cul-
ture was diluted to McFarland 2 standard with the similar
medium. From this, 50 lL of this bacterial culture was
1
(CH=N); H-NMR (300 MHz, DMSO-d6, d ppm): 2.32 (s,
3H, CH3); 2.62–2.90 (m, 8H, piperazine); 4.64 (s, 2H,
–CH2); 6.70–7.92 (m, 12H, Ar–CH); 8.30 (s, 1H, Ar–NH);
8.50 (s, 1H, CH=N); 9.87 (s, 1H, CONH); 13C-NMR
(100 MHz, DMSO-d6, d ppm): 38.4 (CH3); 72.4 (2C), 59.8
(2C) (Piperazinyl); 73.8 (CH2); 112.8, 126.4, 130.8 (CH,
Indolyl); 114.4 (2C), 118.5, 124.9 (2C), 128.3 (2C), 129.3
(2C) (CHarom); 131.9, 132.8, 136.6 (C, Indolyl); 134.5,
137.5, 141.2 (Carom); 142.5 (C=N); 163.6 (C=O, Urea);
177.6, 180.6 (C=O, Indolyl). MS (EI) m/z: 496 [M?]; Anal.
Calcd for C28H28N6O3: C, 67.73; H, 5.68; N, 16.92. Found:
C, 67.94; H, 5.70; N, 16.98.
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