Arch. Pharm. Chem. Life Sci. 2013, 346, 901–911
Benzophenone-Integrated Coumarin Analogs as Novel Anticancer Agents
909
Ar–CH3), 4.6 (s, 2H, CH2), 7.1–8.0 (m, 11H, Ar–H), 8.7 (s, 1H,
coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 491. Anal.
calcd. for C26H19ClN2O6: C, 63.61; H, 3.90; N, 5.71. Found: C, 63.68;
H, 3.97; N, 5.80%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-methyl-4-
(3-methyl-benzoyl)-phenoxy]-acetyl}-hydrazide
–
8j: Yield 80%. m.p. 200–204°C; IR (Nujol): 1625 (C O), 1675 (amide
–
–
C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.2 (s, 3H,
ꢄ1
–
Ar–CH3), 2.3 (S, 3H, CH3), 4.1 (s, 2H, CH2), 7.3–8.3 (m, 11H, Ar–H),
8.7 (s, 1H, coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 471.
Anal. calcd. for C27H22N2O6: C, 68.93; H, 4.71; N, 5.95. Found: C,
68.99; H, 4.77; N, 5.96%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[4-(2-bromo-
benzoyl)-2-methyl-phenoxy]-acetyl}-hydrazide
–
8d: Yield 85%. m.p. 202–205°C; IR (Nujol): 1625 (C O), 1675
–
ꢄ1
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.5
–
–
(s, 3H, Ar–CH3), 4.3 (s, 2H, CH2), 7.2–8.1 (m, 11H, Ar–H), 8.9 (s, 1H,
coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 536. Anal.
calcd. for C26H19BrN2O6: C, 58.33; H, 3.58; N, 5.23. Found: C, 58.40;
H, 3.65; N, 5.29%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-chloro-6-
fluoro-4-(4-fluoro-benzoyl)-phenoxy]-acetyl}-hydrazide
–
8k: Yield 78%. m.p. 207–209°C; IR (Nujol): 1625 (C O), 1675 (amide
–
–
C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 4.4 (s, 2H,
ꢄ1
–
CH2), 7.2–8.1 (m, 10H, Ar–H), 8.7 (s, 1H, coumarin Ar–H), 10.4–10.9
(d, 2H, –NHNH); MS: m/z 514. Anal. cald. for C25H15ClF2N2O6: C,
58.55; H, 2.95; N, 5.46. Found: C, 58.59; H, 2.99; N, 5.48%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[4-(4-bromo-
benzoyl)-2-methyl-phenoxy]-acetyl}-hydrazide
–
8e: Yield 80%. m.p. 210–212°C; IR (Nujol): 1625 (C O), 1675
–
ꢄ1
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.5
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-chloro-6-
–
–
(s, 3H, Ar–CH3), 4.3 (s, 2H, CH2), 7.1–8.0 (m, 11H, Ar–H), 8.6 (s, 1H,
coumarin Ar–H), 10.6–10.9 (d, 2H, –NHNH); MS: m/z 536. Anal.
calcd. for C26H19BrN2O6: C, 58.33; H, 3.58; N, 5.23. Found: C, 58.40;
H, 3.65; N, 5.29%.
fluoro-4-(4-methyl-benzoyl)-phenoxy]-acetyl}-hydrazide
–
8l: Yield 88%. m.p. 175–177°C; IR (Nujol): 1625 (C O), 1675 (amide
–
ꢄ1
C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.5 (s, 3H,
–
–
Ar–CH3), 4.4 (s, 2H, CH2), 7.1–8.2 (m, 10H, Ar–H), 8.7 (s, 1H,
coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 510. Anal.
calcd. for C26H18ClFN2O6: C, 61.37; H, 3.57; N, 5.50. Found: C,
61.42; H, 3.61; N, 5.53%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[4-(4-fluoro-
benzoyl)-2-methyl-phenoxy]-acetyl}-hydrazide
–
8f: Yield 82%. m.p. 225–228°C; IR (Nujol): 1625 (C O), 1675 (amide
–
–
C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.5 (s, 3H,
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-chloro-6-
ꢄ1
–
Ar–CH3), 4.3 (s, 2H, CH2), 7.1–8.0 (m, 11H, Ar–H), 8.9 (s, 1H,
coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 475. Anal.
calcd. for C26H19FN2O6: C, 65.82; H, 4.04; N, 5.90. Found: C, 65.88;
H, 4.10; N, 5.97%.
fluoro-4-(4-iodo-benzoyl)-phenoxy]-acetyl}-hydrazide
–
8m: Yield 85%. m.p. 235–238°C; IR (Nujol): 1625 (C O), 1675
–
ꢄ1
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 4.2
–
–
(s, 2H, CH2), 7.3–8.4 (m, 10H, Ar–H), 8.5 (s, 1H, coumarin Ar–H), 10.4–
10.9 (d, 2H, –NHNH); MS: m/z 622. Anal. calcd. for C25H15ClFIN2O6: C,
48.37; H, 2.44; N, 4.51. Found: C, 48.42; H, 2.48; N, 4.53%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[4-(4-
methoxy-benzoyl)-2-methyl-phenoxy]-acetyl}-hydrazide
–
8g: Yield 90%. m.p. 197–199°C; IR (Nujol): 1625 (C O), 1675
2-Oxo-2H-chromene-3-carboxylic acid N0-[2-(4-benzoyl-
–
ꢄ1
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.2
–
–
2,6-dimethyl-phenoxy)-acetyl]-hydrazide
(s, 3H, Ar–CH3), 3.7 (S, 3H, OCH3), 4.3 (s, 2H, CH2), 6.7–7.9 (m, 11H,
Ar–H), 8.6 (s, 1H, coumarin Ar–H), 10.5–10.9 (d, 2H, –NHNH); MS:
m/z 487. Anal. calcd. for C27H22N2O7: C, 66.66; H, 4.56; N, 5.76.
Found: C, 66.70; H, 4.59; N, 5.80%.
–
8n: Yield 82%. m.p. 229–232°C; IR (Nujol): 1625 (C O), 1675
–
ꢄ1
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.2
–
–
(s, 3H, Ar–CH3), 2.3 (S, 3H, CH3), 4.6 (s, 2H, CH2), 7.1–8.2 (m, 11H,
Ar–H), 8.8 (s, 1H, coumarin Ar–H), 10.2–10.8 (d, 2H, –NHNH);
MS: m/z 471. Anal. calcd. for C27H22N2O6: C, 68.93; H, 4.71; N, 5.95.
Found: C, 68.99; H, 4.77; N, 5.96%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-methyl-4-
(4-methyl-benzoyl)-phenoxy]-acetyl}-hydrazide
8h: Yield 85%. m.p. 188–191°C; IR (Nujol): 1625 (C O), 1675
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[4-(2,6-
–
–
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.2
ꢄ1
–
–
dichloro-benzoyl)-2-methyl-phenoxy]-acetyl}-hydrazide
(s, 3H, Ar–CH3), 2.5 (S, 3H, CH3), 4.3 (s, 2H, CH2), 7.3–8.2 (m, 11H,
Ar–H), 8.9 (s, 1H, coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH);
MS: m/z 471. Anal. calcd. for C27H22N2O6: C, 68.93; H, 4.71; N, 5.95.
Found: C, 68.99; H, 4.77; N, 5.96%.
–
8o: Yield 70%. m.p. 215–219°C; IR (Nujol): 1625 (C O), 1675
–
(amide C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.3
ꢄ1
–
–
(s, 3H, Ar–CH3), 4.4 (s, 2H, CH2), 7.4–8.3 (m, 10H, Ar–H), 8.6 (s, 1H,
coumarin Ar–H), 10.2–10.7 (d, 2H, –NHNH); MS: m/z 526. Anal.
calcd. for C26H18Cl2N2O6: C, 59.44; H, 3.45; N, 5.33. Found: C,
59.49; H, 3.50; N, 5.38%.
2-Oxo-2H-chromene-3-carboxylic acid N0-{2-[2-methyl-4-
(2-methyl-benzoyl)-phenoxy]-acetyl}-hydrazide
–
8i: Yield 78%. m.p. 178–180°C; IR (Nujol): 1625 (C O), 1675 (amide
–
–
Biology
C O), 3130–3240 cm (NH–NH); 1H NMR (CDCl3): d 2.2 (s, 3H,
ꢄ1
–
Ar–CH3), 2.4 (S, 3H, CH3), 4.4 (s, 2H, CH2), 7.2–8.2 (m, 11H, Ar–H),
8.8 (s, 1H, coumarin Ar–H), 10.4–10.9 (d, 2H, –NHNH); MS: m/z 471.
Anal. calcd. for C27H22N2O6: C, 68.93; H, 4.71; N, 5.95. Found:
C, 68.99; H, 4.77; N, 5.96%.
Cell culture and in vitro compounds treatment
MCF-7 breast cancer cells were procured from National
Centre for Cell Sciences (NCCS), Pune, India. MCF-7 cells were
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