Vol. 26, No. 24 (2014)
Synthesis, Characterization, Antiamoebic Activity and Toxicity of Ferrocenyl Chalcones 8409
1-Ferrocenyl-3-phenyl-2-propen-1-one (10): Yield 70
%; m.p.: 122 °C; deep red solid; Anal. calc. for C19H16FeO: C
Hα), 4.95 (s, 2H, ferrocene), 4.61 (s, 2H, ferrocene), 4.24 (s,
5H, ferrocene); 13C NMR (CDCl3) δ (ppm): 192.23 (C=O),
145.14 (C-β), (135.70, 130.02, 129.53,128.51, aromatic),
122.52 (C-α). ESI-MS m/z: [M+ + 1] 351.62.
72.17, H 5.10 %. Found: C 72.14; H 5.07 %. IR (KBr, νmax
,
cm-1): 3033 (Ar-H), 2938 (C-H), 1645 (C=O), 1580 (C=C);
1H NMR (CDCl3) δ (ppm): 7.89 ( d, 2H, J = 8.7 Hz, Ar-H),
7.75 (d, 1H, J = 15.2 Hz, Hβ), 7.65-7.16 (m, 4H, Ar-H, Hα),
4.92 (s, 2H, ferrocene), 4.59 (s, 2H, ferrocene), 4.22 (s, 5H,
ferrocene); 13C NMR (CDCl3) δ (ppm): 193.04 (C=O), 144.41
(C-β), (136.07, 134.70, 130.02, 128.51, aromatic), 122.52
(C-a). ESI-MS m/z: [M+ +1] 316.1.
1-Ferrocenyl-3-(3,4-dimethylphenyl)-2-propen-1-one
(16): Yield 72 %; m.p.: 138 °C; deep red solid; Anal. calc. for
C21H20FeO: C 73.27, H, 5.86 %. Found: C 73.23, H 5.87 %.
IR (KBr, νmax, cm-1): 3068 (Ar-H), 2949 (C-H), 1650 (C=O),
1
1577 (C=C); H NMR (CDCl3) δ (ppm): 7.81-7.76 (m, 2H,
Ar-H), 7.73 (d, 1H, J = 15 Hz, Hβ), 7.58-7.29 (m, 2H, Ar-H,
Hα), 4.92 (s, 2H, ferrocene), 4.58 (s, 2H, ferrocene), 4.23 (s,
5H, ferrocene), 2.24 (s, 3H, CH3), 2.16 (s,1H, CH3); 13C NMR
(CDCl3) δ (ppm): 193.49 (C=O), 144.78 (C-β), (135.51, 132.72,
128.92, 128.63,Aromatic), 122.09 (C-α). 22.45 (methyl). ESI-
MS m/z: [M+ + 1] 345.21.
1-Ferrocenyl-3-p-tolyl-2-propen-1-one (11): Yield 74 %;
m.p.: 164 °C; deep red solid; Anal. calc. for C20H18FeO: C
72.75, H 5.49 %. Found: C 72.72; H 5.42 %. IR (KBr, νmax
,
cm-1): 3036 (Ar-H), 2931 (C-H), 1641 (C=O), 1582 (C=C);
1H NMR (CDCl3) δ (ppm): 7.88-7.81 (m, 2H, Ar-H), 7.73 (d,
1H, J = 15.6 Hz, Hβ), 7.57-7.24 (m, 3H, Ar-H, Hα), 4.95 (s,
2H, ferrocene), 4.61 (s, 2H, ferrocene), 4.24 (s, 5H, ferrocene),
2.41 (s, 3H, CH3); 13C NMR (CDCl3) δ (ppm): 192.83 (C=O),
144.68 (C-β), (135.07, 131.70, 139.02, 128.51, aromatic),
122.89 (C-α), 21.51 (CH3). ESI-MS m/z: [M+ + 1] 331.00
1-Ferrocenyl-3-(2,5-dimethoxyphenyl)-2-propen-1-one
(12): Yield 80 %; deep red liquid; Anal. calc. for C21H20FeO3:
C 67.04, H 5.36. Found: C 67.06, H 5.32 % IR (KBr, νmax, cm-1):
3044 (Ar-H), 2931 (C-H), 1651 (C=O), 1580 (C=C); 1H NMR
(CDCl3) δ (ppm): 7.81 (s, 1H, Ar-H), 7.76 (d, 1H, J = 16 Hz,
Hβ), 7.59-7.42 (m, 2H, Ar-H), 7.36 (d, 1H, J = 16 Hz, Hα),
4.93 (s, 2H, ferrocene), 4.57 (s, 2H, ferrocene), 4.22 (s, 5H,
ferrocene), 3.91 (s, 3H, OCH3), 3.73 (s, 3H, OCH3); 13C NMR
(CDCl3) δ (ppm): 192.18 (C=O), 143.65 (C-β), (135.61,
132.70, 130.02, 128.51, aromatic), 122.23 (C-α), 55.65
(OCH3). ESI-MS m/z: [M+ +1] 376.21.
1-Ferrocenyl-3-(4-methylsulfanyl phenyl)-2-propen-1-
one (17): Yield 72 %; m.p.: 157 °C; deep red solid;Anal. calc.
for C21H20FeOS : C 66.31, H 5.01 %. Found: C 66.28, H 5.03 %.
IR (KBr, νmax, cm-1): 3068 (Ar-H), 2949 (C-H), 1685 (C=O),
1
1587 (C=C); H NMR (CDCl3) δ (ppm): 7.83-7.79 (m, 2H,
Ar-H), 7.74 (d, 1H, J = 15.6 Hz, Hβ), 7.56-7.43 (m, 2H, Ar-
H), 7.33 (d, 1H, J = 15.6 Hz, Hα), 4.94 (s, 2H, ferrocene), 4.59
(s, 2H, ferrocene), 4.21 (s, 5H, ferrocene), 2.42 (s, 3H, CH3).
13C NMR (CDCl3) δ (ppm): 192.89 (C=O), 143.87 (C-β),
(135.51, 132.72, 128.92, 128.63, aromatic), 122.14 (C-α). 16.9
(SCH3). ESI-MS m/z: [M+ + 1] 376.20.
1-Ferrocenyl-3-(4-nitrophenyl)-2-propen-1-one (18):
Yield 74 %; m.p.: 145 °C; deep red solid; Anal. calc. for
C19H15FeNO3 : C 63.18, H 4.19, N 3.88 %. Found: C 63.21, H
4.15 N 3.85 %. IR (KBr, νmax, cm-1): 3068 (Ar-H), 2935 (C-H),
1
1648 (C=O), 1579 (C=C); H NMR (CDCl3) δ (ppm) 8.13-
1-Ferrocenyl-3-(4-methoxyphenyl)-2-propen-1-one
(13): Yield 72 %; m.p.: 121 °C; deep red solid; Anal. calc. for
C20H18FeO2: C 69.39, H 5.24 %. Found: C 69.35, H 5.26 % IR
(KBr, νmax, cm-1): 3028 (Ar-H), 2916 (C-H), 1643 (C=O), 1574
(C=C); 1H NMR (CDCl3) δ (ppm): 7.88 -7.83 ( m, 2H, Ar-H),
7.81 (d, 1H, J = 15.6 Hz, Hβ), 7.68-7.54 (m, 2H, Ar-H,), 7.37
(d, J = 15.6 Hz, Hα) 4.92 (s, 2H, ferrocene), 4.58 (s, 2H,
ferrocene), 4.24 (s, 5H, ferrocene), 3.84 (s, 3H, OCH3); 13C
NMR (CDCl3) δ (ppm): 192.27 (C=O), 144.44 (C-β), (135.07,
131.99, 129.92, 128.63, aromatic), 122.93 (C-α), 56.23
(OCH3). ESI-MS m/z: [M+ + 1] 347.20
1-Ferrocenyl-3-(3,4,5-trimethoxyphenyl)-2-propen-1-
one (14): Yield 78 %; deep red liquid; Anal. calc. for
C22H22FeO4: C 65.04, H 5.46 %. Found: C, 65.06, H 5.42 %
IR (KBr, νmax, cm-1): 3051 (Ar-H), 2930 (C-H), 1650 (C=O),
1565 (C=C); 1H NMR (CDCl3) δ (ppm): 7.79 (s, 1H, Ar-H),
7.74 (d, 1H, J = 15.2 Hz, Hβ), 7.69 (s, 1H, Ar-H), 7.38 (d, 1H,
J = 15 Hz, Hα), 4.96 (s, 2H, ferrocene), 4.58 (s, 2H, ferrocene),
4.22 (s, 5H, ferrocene), 3.85 (s, 6H, OCH3), 3.82 (s, 3H, OCH3);
13C NMR (CDCl3) δ (ppm): 192.43 (C=O), 143.49 (C-β),
(135.07, 130.70, 139.02, 128.51, aromatic), 122.42 (C-α),
60.91, 56.54 ( OCH3). ESI-MS m/z: [M+ + 1] 406.21
8.05 (m, 2H, Ar-H), 7.74 (d, 1H, J = 15.2 Hz, Hβ), 7.61-7.17
(m, 3H, Ar-H, Hα), 4.93 (s, 2H, ferrocene), 4.49 (s, 2H, ferro-
cene), 4.21 (s, 5H, ferrocene); 13C NMR (CDCl3) δ (ppm):
193.04 (C=O), 145.91 (C-β), (135.70, 130.02, 129.53,128.51,
aromatic), 122.72 (C-α). ESI-MS m/z: [M+ + 1] 362.10.
in vitro Antiamoebic assay: All compounds 1-18 were
screened in vitro for antiamoebic activity against HM1:IMSS
strain of E. histolytica by microdilution method31. E. histolytica
trophozoites were cultured in wells of 96-well microtiter plate
by using diamond TYIS-33 growth medium32. The test com-
pounds (1 mg) were dissolved in DMSO (40 mL, level at which
no inhibition of amoeba occurs)33,34. The stock solutions of
the compounds were prepared freshly before use at a concen-
tration of 1 mg/mL. Two-fold serial dilutions were made in
the wells of 96-well microtiter plate (costar). Each test includes
metronidazole as a standard amoebicidal drug, control wells
(culture medium plus amoebae) and a blank (culture medium
only).All the experiments were carried out in triplicate at each
concentration level and repeated thrice. The amoeba suspen-
sion was prepared from a confluent culture by pouring off the
medium at 37 °C and adding 5 mL of fresh medium, chilling
the culture tube on ice to detach the organisms from the side
of the flask. The number of amoeba/mL was estimated with a
haemocytometer, using trypan blue exclusion to confirm the
viability. The suspension was diluted to 105 organism/mL by
adding fresh medium and 170 mL of this suspension was added
to the test and control wells in the plate so that the wells were
completely filled (total volume, 340 mL). An inoculum of
1-Ferrocenyl-3-(4-chlorophenyl)-2-propen-1-one (15):
Yield 74 %; m.p.: 140 °C; deep red solid; Anal. calc. for
C19H15OClFe: C 65.09, H 4.31 %. Found: C, 65.06; H 4.26 %
IR (KBr, νmax, cm-1): 3068 (Ar-H), 2932 (C-H), 1642 (C=O),
1
1578 (C=C); H NMR (CDCl3) δ (ppm) 7.81-7.74 (m, 2H,
Ar-H), 7.68 (d, 1H, J = 15.6 Hz, Hβ), 7.51-7.26 (m, 3H, Ar-H,