Synthesis, structure and cytotoxicity of new 2-[(3-aminopropyl) dimethylsilyl]-5-furfural diethylacetals and 2-[(3-aminopropyl)dimethylsilyl]-5- phenylfurans

Article abstract of DOI:10.1002/aoc.2995

Novel 2-[(3-aminopropyl)dimethylsilyl]-5-furfural diethylacetals and 2-[(3-aminopropyl)di-methylsilyl]-5-phenylfurans have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N-allylamines in the presence of the Speier's catalyst. The effects of the structure of the amine and nature of organic substituent at the furan ring on the cytotoxicity of the new compounds have been studied. Copyright

Full text of DOI:10.1002/aoc.2995

Full Paper
Received: 19 December 2012
Revised: 18 March 2013
Accepted: 18 March 2013
Published online in Wiley Online Library: 28 May 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.2995
Synthesis, structure and cytotoxicity of new
2-[(3-aminopropyl)dimethylsilyl]-5-furfural
diethylacetals and 2-[(3-aminopropyl)
dimethylsilyl]-5-phenylfurans
Luba Ignatovich*, Velta Muravenko, Jana Spura, Jury Popelis,
Ilona Domrachova and Irina Shestakova
Novel 2-[(3-aminopropyl)dimethylsilyl]-5-furfural diethylacetals and 2-[(3-aminopropyl)di-methylsilyl]-5-phenylfurans have
been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N-allylamines in the presence of the Speier’s
catalyst. The effects of the structure of the amine and nature of organic substituent at the furan ring on the cytotoxicity of
the new compounds have been studied. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: 2-[(3-aminopropyl)dimethylsilyl]-5-furfural diethylacetals; 2-[(3-aminopropyl)-dimethylsilyl]-5-phenylfurans; hydrosilylation;
1H, 13C, 29Si NMR; cytotoxic activity
chromatography was performed on silica gel (0.060–0.200 mm,
Introduction
pore diameter 6 nm (‘Acros’). 5-Dimethylsilylfurfural diethylacetal (1)
has been prepared by known methods.[3]
Previously we studied the synthesis and cytotoxic activity of
2-[(3-aminopropyl)-dimethylsilyl]-5-trialkylsilyl(germyl)furans.[1,2]
Our investigations have demonstrated that these types of com-
pounds have high cytotoxic activity on two cell tumor lines, viz.
HT-1080 (human fibrosarcoma) and MG-22A (mouse hepatoma),
Cytotoxicity In Vitro
but unfortunately these compounds possess high cytotoxic
activity towards normal NIH 3 T3 cells (normal mouse embryonic
fibroblasts) as well as relatively high toxicity. In order to search for
new substances with low toxicity (LD50) that are highly toxic to can-
cer cells but not toxic to normal cells, we synthesized a new series
of aminopropylsilylfurans with organic substituent in the furan ring
and studied the cytotoxicity of the obtained novel compounds.
Monolayer tumor cell lines MG-22A (mouse hepatoma), HT-1080
(human connective tissue fibrosarcoma) and NIH 3 T3 (normal
mouse fibroblasts) were cultivated for 72 h in standard
Dulbecco’s modified Eagle’s medium (Sigma) without indicator
and antibiotics.[4] After the ampoule was thawed not more than
four passages were performed. The control cells and cells with
tested substances in the range of 2–5 Â 104 cells mlÀ1 concentra-
tion (depending on line nature) were placed on separate 96-well
plates. Solutions containing test compounds were diluted and
added to wells to give final concentrations of 50, 25, 12.5 and
6.25 mg mlÀ1. The control cells were treated in the same manner
but in the absence of test compounds. Plates were cultivated
for 72 h. The quantity of surviving cells was determined using
Crystal Violet (CV), Neutral Red (NR) or 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyl-2H-tetrazolium bromide (MTT) coloration, which was
assayed by multiscan spectrophotometer (Tetretek Multiscan
MCC/340). The quantity of living cells on the control plate was
taken in calculations as 100% (IC50 determination).[4,5] The concen-
tration of NO was determined according to Fast et al.[5] The mean
lethal dose (LD50) was determined on NIH 3 T3 cells (alternative
to LD in vivo test) according to the protocols of the Interagency
Experimental
Materials and Methods
The 1H, 13C and 29Si NMR spectra were recorded on a Varian 400
Mercury spectrometer at 400, 100 and 80 MHz, respectively, in
CDCl3 as a solvent, with (Me3Si)2O as a standard for 1H,
tetramethylsilane (external) as the standard for 29Si, and the
signal on the residual proton of the solvent (d 77.05 ppm) for
13C. The mass-spectra under electron impact conditions were
recorded on an Agilent Technologies 7890 gas chromatogra-
phy–mass spectrometry (GC-MS) system with 5975C EI/CI MSD
(70 eV) on an HP-5 capillary column. High-resolution mass spectra
were recorded by Q-TOF micromass electrospray ionization (ESL+).
Elemental analyses were recorded on a CARLO ERBA EA-1108
element analyzer.
*
Correspondence to: L. Ignatovich, Latvian Institute of Organic Synthesis,
21 Aizkraukles, Riga LV 1006, Latvia. E-mail: ign@osi.lv
All solvents were dried over CaH2 and metallic sodium and
distilled prior to use. Thin-layer chromatography (TLC) was
performed on Merck silica gel 60 F254 with various eluents. Column
Latvian Institute of Organic Synthesis, RigaLV 1006, Latvia
Appl. Organometal. Chem. 2013, 27, 406–411
Copyright © 2013 John Wiley & Sons, Ltd.

New 2-[(3-aminopropyl)dimethylsilyl]-5-organylfurans
Coordinating Committee on the Validation of Alternative
Methods and the National Toxicology Program of the Interagency
Center for the Evaluation of Alternative Toxicological Methods.[6]
159.43 C2. 29Si NMR d ppm: À9.40. GC-MS, m/z (%): 341 (M+, 12),
296 (M+ À OEt, 28), 238 (6), 155 (45), 142 (12), 112 (20), 97 (7), 86
(100), 59 (20). HR-MS calcd for C18H36NO3Si (M+, 10) 342.2067,
found 342.2057. Anal. Calcd for C18H35NO3Si: C, 63.30; H, 10.33; N
4.10. Found: C, 63.08; H, 10.18; N, 3.98.
Chemistry
Compounds 4–21 were isolated and purified in the same
manner as described for compound 3.
Synthesis of 2-dimethylsilyl-5-phenylfuran (2)
A solution of 2-phenylfuran (16.6 mmol) in dry ether (35 ml) was
placed in a three-necked flask fitted with a reflux condenser,
thermometer, magnetic stirrer and a rubber stopper in a stream
of argon. The flask with the solution was cooled to À30 ꢀC, and a
solution of 2.5 N n-BuLi (16.6mmol) in hexane was added dropwise
slowly to maintain the temperature below À25 ꢀC. When all the
n-BuLi had been added, the mixture was stirred for 30 min at
À25 ꢀC, and for 2 h at 20 ꢀC. Then, dimethylchlorosilane
(16.6 mmol) was added dropwise at À10 Ä À15 ꢀC. After the
addition of dimethylchlorosilane the mixture was stirred for
10 min at À15 ꢀC, the temperature was slowly raised to room
temperature and the mixture was stirred for 12 h. The precipitate
was filtered through Al2O3, the solvents were evaporated and
the residue was distilled under reduced pressure at 106–108 ꢀC
(5 mmHg), to give 1.93 g (57.6%) of compound 2.1H NMR
d ppm (J, Hz): 0.38 (6H, s, Si-CH3); 4.44–4.48 (1H, m, Si-H); 6.64
(1H, d, H4, J = 3.6 Hz); 6.74 (1H, d, H3, J = 3.6 Hz); 7.23–7.26 (1H,
m, C6H5), 7.35–7.40 (2H, m, C6H5), 7.62–7.72 (2H, m, C6H5);
13C NMR d ppm: À4.46 Si-CH3, 105.29 C4, 122.98 C3, 124.16
C6H5, 127.47 C6H5, 128.65 C6H5, 131.04 C6H5, 156.88 C5, 158.47
C2. 29Si NMR, d ppm: À28.49. GC-MS, m/z (%): 202 (M+, 37), 187
(M+ À Me, 100), 171 (5), 161 (40), 145 (9), 127 (13), 115 (25), 105
(11), 87 (11), 77 (33), 61 (12), 51 (14). Anal. Calcd for C12H14OSi:
C, 71.24; H, 6.97. Found: C, 71.08; H, 6.88.
N,N-Dibutyl-{3-[dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}amine (4)
Compound 4 was prepared from compound 1 and N,N-di-n-
butylallylamine by stirring for 1 h at room temperature (during
the first 45 min a violent reaction took place). Yield: 70.4%
1
(light-brown oil). H NMR d ppm: 0.23 (s, 6H, Si-CH3), 0.66–0.71
(m, 2H, Si-CH2), 0.90 (t, 6H, C-CH3, J = 7.2 Hz), 1.19–1.23 (t, 6H,
C-CH3, J = 7.2 Hz), 1.25–1.48 (m, 10H, C-CH2), 2.35–2.40 (m, 6H, N-
CH2), 3.53–3.65 (m, 4H, O-CH2), 5.55 (s, 1H, CH), 6.38 (d, 1H, H4,
J
3,4 = 3.2Hz), 6.56 (d, 1H, H3, J3,4 = 3.2 Hz). 13C NMR d ppm: À3.38
Si-CH3, 12.77 C-CH3 , 14.08 C-CH3, 15.17 Si-CH2, 20.76 C-CH2, 21.23
CH2-CH3, 29.17 C-CH2, 53.88 N-CH2 , 57.59 N-CH2, 61.12 O-CH2,
96.56 O-CH, 107.90 C3, 120.41 C4, 156.23 C5, 159.48 C2. 29Si NMR
d ppm: À9.24. GC-MS, m/z (%): 397 (M+, 11), 382 (M+ À Me, 5),
352 (M+ – Me, 65), 294 (11), 228 (5), 183 (66), 170 (46), 153
(89), 142 (100), 128 (33), 119 (53), 109 (32), 100 (88), 41 (83), 75
(41), 59 (39). HR-MS calcd for C22H44NO3Si (M+, 100) 398.3090,
found 398.3133. Anal. Calcd for C22H43NO3Si: C, 66.45; H, 10.90; N
3.52. Found: C, 66.28; H, 10.79; N, 3.40.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}pyrrolidine (5)
Compound
5 was prepared from compound 1 and N-
allylpyrrolidine by stirring for 1.2 h at room temperature (during
the first15 min a violent reaction took place) followed by heating
at 90 ꢀC for 15 min. Yield 73.2% (light-brown oil). 1H NMR d ppm:
0.23 (s, 6H, Si-CH3), 0.72–0.76 (m, 2H, Si-CH2); 1.21 (t, 6H, C-CH3,
J = 7.2 Hz,), 1.49–1.60 (m, 2H, C-CH2); 1.70–1.80 (m, 4H, C-CH2);
2.39–2.55 (m, 6H, N-CH2), 3.55–3.67 (m, 4H, O-CH2), 5.55 (s, 1H,
CH), 6.37 (d, 1H, H4, J3,4 = 3.2 Hz), 6.56 (d, 1H, H3, J3,4 = 3.2 Hz).
13C NMR d ppm: À3.45 Si-CH3, 13.00 C-CH3, 15.16 Si-CH2, 23.18
C-CH2, 23.35 C-CH2, 54.11 N-CH2, 59.82 N-CH2, 61.12 O-CH2,
96.54 O-CH, 107.89 C3, 120.45 C4, 156.22 C5, 159.350 C2. 29Si
NMR d ppm: À9.35. GS-MS, m/z (%): 294 (M+ – EtO, 9), 153 (8),
110 (7), 84 (100), 59 (5). HRMS calcd for C18H34NO3Si (M+, 10)
340.2308, found 340.2307. Anal. Calcd for C18H33NO3Si: C, 63.67;
H, 9.80; N 4.13. Found: C, 63.38; H, 9.98; N, 4.03.
General Synthetic Procedure and Structural Elucidation
To a solution of 5-dimethylsilyl-2-furfural diethylacetal or 5-
dimethylsilyl-5-phenylfuran (1 mmol) and corresponding allylamine
(1mmol) two drops of 0.1% H2PtCl6.6H2O solution in 2-PrOH
were added to a flask equipped with a reflux condenser and
magnetic stirrer. The reaction course was monitored by TLC
and GC-MS. In some cases an exothermic reaction occurred
immediately and in other cases by heating for 15–150 min. The
product was separated and purified using a chromatography
column with CH2Cl2–MeOH (10:1) as eluent. These experimental
conditions led to expected products in good yields. The new com-
pounds were identified by NMR (1H, 13C and 29Si), GC-MS, elemental
analysis and high-resolution mass spectrometry (HR-MS).
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}piperidine (6)
Compound
6 was prepared from compound 1 and N-
N,N-Diethyl-{3-[dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}amine (3)
allylpiperidine by stirring for 1.2 h at room temperature (during
the first 10 min a violent reaction took place) followed by heating
at 90 ꢀC for 15 min. Yield 78.8 % (light-brown oil). 1H NMR d ppm:
0.22 (s, 6H, Si-CH3), 0.65–0.70 (m, 2H, Si-CH2); 1.20 (t, 6H, C-CH3
J = 7.2 Hz), 1.34–1.60 (m, 8H, C-CH2); 2.23–2.40 (m, 6H, N-CH2),
3.55–3.65 (m, 4H, O-CH2), 5.53 (s, 1H, CH), 6.36 (d, 1H, , H4,
Compound 3 was prepared from compound 1 and N,N-
diethylallylamine by stirring for 30 min at room temperature
(during the first 10min a violent reaction took place), followed
by heating at 90ꢀC for 1 h, then cooling and analysis by GC-MS.
After purification by column chromatography using CH2Cl2–MeOH
(10:1) as eluent and removal of the solvents a light-brown oil
J
3,4 = 3.2 Hz), 6.53 (d, 1H, , H3, J3,4 = 3.2 Hz). 13C NMR d ppm:
1
was obtained. Yield: 61.2%. H NMR d ppm: 0.23 (s, 6H, Si-CH3),
À3.40 Si-CH3, 12.96 C-CH3, 15.18 Si-CH2, 21.10 C-CH2, 24.49
C-CH2, 25.98 C-CH2, 54.62 N-CH2, 61.14 N-CH2, 62.93 O-CH2, 96.56
O-CH, 107.91 C3, 120.46 C4, 156.24 C5, 159.40 C2. 29Si NMR d ppm:
À9.34. GS-MS, m/z (%): 353 (M+, 5), 338 (M+ À Me, 4), 308
(M+ À EtO, 16), 250 (6), 182 (5) 153 (17), 124 (11), 98 (100), 75 (9),
59 (9). HR-MS calcd for C19H36NO3Si (M+, 12) 354.2464, found
354.2453. Anal. Calcd for C19H35NO3Si: C, 64.54; H, 9.98; N 3.36.
Found: C, 64.36; H, 9.68; N, 3.29.
0.67–0.71 (m, 2H, Si-CH2), 1.00 (t, 6H, C-CH3, J = 7.2Hz), 1.21
(t, 6H, C-CH3, J = 7.2Hz), 1.44–1.52 (m, 2H, C-CH2), 2.37–2.41
(m, 2H, N-CH2), 2.45–2.52 (m, 4H, N-CH2), 3.50–3.67 (m, 4H, O-CH2),
5.55 (s, 1H, CH), 6.37 (d, 1H, H4, J3,4 = 3.2 Hz), 6.56 (d, 1H, H3,
J
3,4 = 3.2 Hz). 13C NMR d ppm: À3.38 Si-CH3, 11.66 C-CH3, 12.88
C-CH3, 15.18 Si-CH2, 21.27 C-CH2, 46.89 N-CH2, 56.42 N-CH2,
61.15 O-CH2, 96.57 O-CH, 107.91 C3, 120.46 C4, 156.25 C5,
Appl. Organometal. Chem. 2013, 27, 406–411
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

L. Ignatovich et al.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}-2-methylpiperidine (7)
(during the first 5 min a violent reaction took place) followed by
heating at 90 ꢀC for 1.5 h. Yield: 61.5% (yellow oil). 1H NMR d
ppm: 0.23 (s, 6H, Si-CH3), 0.66–0.70 (m, 2H, Si-CH2), 1.21 (t, 6H,
C-CH3, J = 7.0 Hz), 1.43–1.60 (m, 2H, C-CH2), 2.31–2.34 (m, 2H,
N-CH2), 2.62–2.72 (m, 8H, N-CH2, S-CH2), 3.52–3.67 (m, 4H, O-CH2),
5.55 (s, 1H, CH), 6.38 (d, 1H, H4, J3,4 = 3.2 Hz ), 6.56 (d,1H, H3,
Compound 7 was prepared from compound 1 and N-allyl-2-
methylpiperidine by stirring for 20 min at room temperature
(during the first 5 min a violent reaction took place) followed by
1
heating at 90 ꢀC for 1 h. Yield: 66.1% (light-brown oil). H NMR
d ppm: 0.21 (s, 6H, Si-CH3), 0.61–0.66 (m, 2H, Si-CH2); 1.01(d, 3H,
CH3, J = 6.0 Hz), 1.20 (t, 6H, C-CH3, J = 7.0 Hz), 1.25–1.30 (m, 2H,
C-CH2), 1.41–1.66 (m, 6H, C-CH2), 2.03–2.40 (m, 3H, N-CH2),
2.55–2.65 (m, 1H, N-CH2), 2.79–2.85 (m, 1H, N-CH), 3.51–3.63
(m, 4H, O-CH2), 5.52 (s, 1H, CH), 6.36 (d,1H, H4, J3,4 = 3.2 Hz),
6.53 (d,1H, H3, J3,4 = 3.2 Hz). 13C NMR d ppm: À3.39 Si-CH3,
12.96 C-CH3, 15.17 Si-CH2, 19.53 C-CH3, 24.07 C-CH2, 26.16
C-CH2, 34.64 C-CH2, 52.27 N-CH2, 55.84 N-CH2, 57.60 CH2-CH3,
61.13 O-CH2, 96.55 O-CH, 107.91 C3, 120.455 C4, 156.24 C5, 159.39
C2. 29Si NMR d ppm:À 9.37. GS-MS, m/z (%): 367 (M+, 6), 352
(M+ À Me, 7), 322 (M+ À EtO, 19), 153 (14), 112 (100), 83 (6),
55 (8). HRMS calcd for C20H38NO3Si (M+, 100) 368.2621, found
368.2582. Anal. Calcd for C20H37NO3Si: C, 65.35; H, 10.15; N
3.81. Found: C, 65.16; H, 10.09; N, 3.72.
J
3,4 =3.2Hz). 13C NMR d ppm: À3.41 Si-CH3, 12.74 C-CH3, 15.17
Si-CH2, 20.66 C-CH2, 27.96 S-CH2, 54.98 N-CH2, 61.12 N-CH2,
62.61 O-CH2, 96.51 O-CH, 107.91 C3, 120.50 C4, 156.27 C5,
159.22 C2, 29Si NMR d ppm: À9.35. GS-MS, m/z (%): 371
(M+, 36), 356 (M+ À Me, 7), 342 (9), 326 (M+ À EtO, 40), 296 (10),
268 (16) 252 (6), 202 (14), 174 (7), 153 (58), 142 (30), 128 (17),
116 (100), 103 (14), 88 (30), 75 (26), 59 (29). HR-MS calcd for
C
18H34NO3SSi (M+, 10) 372.2029, found 372.2057. Anal. Calcd
for C18H33NO3SSi: C, 58.18; H, 8.95; N 3.77; S 8.63. Found: C,
58.04; H, 9.09; N, 3.63; S, 8.55.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}-4-methylpiperazine (11)
Compound 11 was prepared from compound 1 and N-allyl-4-
methypiperazine by stirring for 1 h at room temperature (during
the first 50 min a violent reaction took place). Yield: 64.0% (yellow
oil). 1H NMR d ppm: 0.23 (s, 6H, Si-CH3), 0.68–0.72 (m, 2H, Si-CH2);
1.21 (d, 6H, C-CH3, J = 7.0 Hz), 1.40–1.55 (m, 2H, C-CH2), 2.20–2.58
(m, 13H, N-CH2, CH3), 3.54–3.63 (m, 4H, O-CH2), 5.54 (s, 1H, CH),
6.38 (d, 1H, H4, J3,4 = 3.2 Hz), 6.56 (d, 1H, H3, J3,4 = 3.2 Hz). 13C
NMR d ppm: À3.40 Si-CH3, 12.81 C-CH3, 15.15 Si-CH2, 21.08 C-
CH2, 46.04 C-CH3, 53.17 N-CH2, 55.12 N-CH2, 61.10 N-CH2, 61.94
CH2-CH3, 96.51 CH-O, 107.89 C3, 120.47 C4, 156.24 C5, 159.26
C2. 29Si NMR d ppm: À9.35. GS-MS, m/z (%): 368 (M+, 14), 339
(M+, 14), 323 (M+ À EtO, 49), 197 (6), 153 (16), 141 (13), 129 (8),
113 (100), 97 (12), 85 (7), 70 (82), 59 (17). HR-MS calcd C19H37N2O3Si
(M+, 20) 369.257, found 369.2552. Anal. Calcd for C19H36N2O3Si: C,
61.91; H, 9.85; N 7.60. Found: C, 61.76; H, 9.79; N, 7.46.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}azepane (8)
Compound
8 was prepared from compound 1 and N-
allylhexamethyleneimine by stirring for 25 min at room tempera-
ture (during the first 10 min a violent reaction took place)
followed by heating at 90 ꢀC for 1 h. Yield: 72.5% (light-brown
1
oil). H NMR d ppm: 0.23 (s, 6H, Si-CH3), 0.66–0.70 (m, 2H, Si-CH2),
1.21 (t, 6H, C-CH3, J = 6.8Hz), 1.45–1.67 (m, 10H, C-CH2), 2.42–2.50
(m, 2H, N-CH2), 2.55–2.63 (m, 4H, N-CH2), 3.55–2.65 (m, 4H,
O-CH2), 5.55 (s, 1H, CH), 6.37 (d, 1H, H4, J3,4 = 3.0 Hz), 6.55 (d, 1H,
d, H3, J3,4 = 3.0 Hz). 13C NMR d ppm: À3.37 Si-CH3, 12.77 C-CH3,
15.16 Si-CH2, 21.55 C-CH2, 27.00 C-CH2, 27.86 C-CH2, 55.50 N-CH2,
61.12 N-CH2, 61.62 O-CH2, 96.54 O-CH, 107.89 C3, 120.42 C4,
156.21 C5, 159.44 C2. 29Si NMR d ppm: À9.33. GS-MS, m/z (%): 367
(M+, 20), 352 (M+ À Me, 6), 338 (M+ À Et, 6), 322 (M+ À EtO, 49),
292 (11), 264 (14), 196 (8), 153 (32), 142 (26), 112 (100), 95 (6), 75
(15), 58 (19). HRMS calcd for C20H38NO3Si (M+, 50) 368.2621, found
368.2582. Anal. Calcd for C20H37NO3Si: C, 65.35; H, 10.15; N 3.81.
Found: C, 65.06; H, 10.09; N, 3.61.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}-4-phenylpiperazine (12)
Compound 12 was prepared from compound 1 and N-allyl-4-
phenylpiperazine by stirring for 45 min at room temperature
(during the first 30 min a violent reaction took place) followed
1
by heating at 90 ꢀC for 1 h. Yield: 75.3% (yellow oil). H NMR d
ppm: 0.24 (s, 6H, Si-CH3), 0.71–0.76 (m, 2H, Si-CH2); 1.21 (t, 6H,
C-CH3, J= 7.0 Hz), 1.50–1.60 (m, 2H, C-CH2), 2.30–2.39 (m, 2H, N-
CH2), 2.50–2.58 (m, 4H, N-CH2), 3.17–3.20 (m, 4H, N-CH2), 3.50–3.63
(m, 4H, O-CH2), 5.55 (s, 1H, CH), 6.38 (d, 1H, H4, J3,4 = 3.2 Hz), 6.57
(d, 1H, H3, J3,4 = 3.2 Hz), 6.82–6.85 (m, 1H, C6H5), 6.90–6.95 (m, 2H,
C6H5), 7.23–7.27 (m, 2H, C6H5). 13C NMR d ppm: À3.38 Si-CH3,
12.86 C-CH3, 15.20 Si-CH2, 21.10 C-CH2, 49.13 N-CH2, 53.26 N-CH2,
61.16 N-CH2, 61.97 O-CH2, 96.56 O-CH, 107.95 C3, 116.01 C6H5,
119.61 C6H5, 120.55 C4, 129.07 C6H5, 151.38 C6H5, 156.31 C5, 159.28
C2. 29Si NMR d ppm: À9.30. GS-MS, m/z (%): 430 (M+, 76), 385
(M+ À EtO, 18), 327 (10), 259 (12), 201 (27), 175 (100), 153 (34), 142
(11), 132 (52), 120 (10), 104 (35), 70 (71), 59 (26). HR-MS calcd for
C24H39N2O3Si (M+, 50) 431.2730, found 431.2708. Anal. Calcd for
C24H38N2O3Si: C, 66.94; H, 8.89; N 6.51. Found: C, 66.93; H, 9.07; N, 3.43.
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}morpholine (9)
Compound
9 was prepared from compound 1 and N-
allylmorpholine by stirring for 20 min at room temperature
(during the first 5 min a violent reaction took place) followed by
heating at 90 ꢀC for 1 h. Yield: 65.3% (yellow). 1H NMR d ppm:
0.24 (s, 6H, Si-CH3), 0.70–0.74 (m, 2H, Si-CH2), 1.21 (t, 6H, C-CH3,
J = 7.2Hz), 1.45–1.60 (m, 2H, C-CH2); 2.30 (t, 2H, N-CH2, J = 8.0Hz),
2.35–2.45 (m, 4H, N-CH2), 3.50–3.65 (m, 4H, O-CH2), 3.69–3.75
(m, 4H, O-CH2), 5.55 (s, 1H, CH), 6.38 (d, 1H, H4, J3,4 = 3.2 Hz), 6.56
(d, 1H, H3, J3,4 = 3.2 Hz). 13C NMR d ppm: À3.43 Si-CH3, 12.73
C-CH3, 15.16 Si-CH2, 20.76 C-CH2, 53.72 N-CH2, 61.12 N-CH2,
62.30 O-CH2, 66.98 O-CH2, 96.51 O-CH, 107.91 C3, 120.51 C4,
156.27 C5, 159.22 C2. 29Si NMR d ppm: À9.34. GS-MS, m/z (%): 355
(M+, 13), 340 (M+ À Me, 5), 310 (M+ À EtO, 22), 280 (9), 252 (14),
186 (9), 153 (34), 142 (10), 126 (23), 100 (100), 75 (21), 59 (23).
HR-MS calcd for C18H34NO4Si (M+, 5) 356.2257, found 356.2282.
Anal. Calcd for C18H33NO4Si: C, 60.81; H, 9.36; N 3.94. Found:
C, 60.96; H, 9.29; N, 3.65.
N,N-Diethyl-{3-[dimethyl(5-phenylfuran-2-yl)silyl]propyl}amine (13)
Compound 13 was prepared from compound 2 and N,N-
diethylallylamine by stirring and heating at 90 ꢀC for 1 h. Yield:
65.4% (light-brown oil). 1H NMR d ppm: 0.28 (s, 6H, Si-CH3),
0.71–0.75 (m, 2H, Si-CH2), 0.98 (t, 6H, C-CH3, J = 7.2Hz), 1.50–1.58
(m, 2H, C-CH2), 2.38–2.42 (m, 2H, N-CH2), 2.46–2.52 (m, 4H, N-CH2),
6.61 (d, 1H, H3, J3,4 = 3.6Hz), 6.66 (d, 1H, H4, J3,4 = 3.6 Hz), 7.19–7.23
1-{3-[Dimethyl(5-diethoxymethylfuran-2-yl)silyl]propyl}thiomorpholine (10)
Compound 10 was prepared from compound 1 and N-
allylthiomorpholine by stirring for 30 min at room temperature
(m, 1H, C6H5), 7.32–7.36 (m, 2H, C6H5), 7.66–7.68 (m, 2H, C6H5). 13
C
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 406–411

New 2-[(3-aminopropyl)dimethylsilyl]-5-organylfurans
NMR d ppm: À3.30 Si-CH3, 11.68 C-CH3, 13.00 Si-CH2, 21.38 C-CH2,
46.91 N-CH2, 56.47 N-CH2, 105.10 C4, 121.93 C3, 124.01 C6H5,
127.24 C6H5, 128.55 C6H5, 131.16 C6H5, 157.88 C5, 159.28 C2. 29Si
NMR d ppm: À9.28. GC-MS, m/z (%): 315 (M+, 15), 300 (M+ À Me,
5), 201 (11), 157 (18), 127 (11), 99 (10), 86 (100), 75 (17), 58 (21).
HRMS calcd for C19H30NOSi (M+, 20) 316.2097, found 316.2105.
Anal. Calcd for C19H29NOSi: C, 72.33; H, 9.27; N 4.44. Found:
C, 72.26; H, 9.30; N, 4.36.
67.5 % (brown oil). 1H NMR d ppm: 0.29 (s, 6H, Si-CH3),
0.68–0.73 (m, 2H, Si-CH2), 1.02 (d, 3H, C-CH3, J = 6.4 Hz),
1.25–1.28 (m, 2H, C-CH2), 1.50–1.68 (m, 6H, C-CH2), 2.13–2.38
(m, 3H, N-CH2), 2.62–2.68 (m, 1H, N-CH2), 2.83–2.86 (m, 1H, N-CH)
6.62 (d, 1H, H3, J3,4 = 3.2Hz), 6.68 (d, 1H, H4, J3,4 = 3.2 Hz), 7.22–7.27
(m, 1H, C6H5), 7.34–7.38 (m, 2H, C6H5), 7.67–7.70 (m, 2H, C6H5). 13
C
NMR d ppm: À3.23 Si-CH3, 13.13 Si-CH2, 19.31 C-CH3, 24.18 C-CH2,
26.20 C-CH2, 34.74 C-CH2, 52.37 N-CH2, 55.92 N-CH2, 57.69 C-CH3,
105.16 C4, 121.99 C3, 124.09 C6H5, 127.32 C6H5, 128.62 C6H5,
131.21 C6H5, 157.94 C5, 159.33 C2. 29Si NMR d ppm: À9.26. GS-MS,
m/z (%): 341 (M+, 24), 326 (M+ À Me, 18), 201 (19), 182 (12), 155
(7), 145 (30), 127 (20), 112 (100), 99 (23), 75 (39), 55 (53). HR-MS calcd
for C21H32NOSi (M+, 100), 342.2253, found 342.2266. Anal. Calcd for
C21H31NOSi: C, 73.85; H, 9.15; N 4.01. Found: C, 73.66; H, 9.23; N, 4.00.
N,N-Dibutyl-{3-[dimethyl(5-phenylfuran-2-yl)silyl]propyl}amine (14)
Compound 14 was prepared from compound 2 and N,N-di-n-
butylallylamine by stirring and heating at 90 ꢀC for 1 h. Yield:
1
72.6% (brown oil). H NMR d ppm: 0.28 (s, 6H, Si-CH3), 0.71–0.75
(m, 2H, Si-CH2), 0.87 (t, 6H, C-CH3, J = 7.2 Hz), 1.21–1.57 (m, 10H,
C-CH2), 2.35–2.45 (m, 6H, N-CH2), 6.61 (d, 1H, H3, J3,4 = 3.6 Hz),
6.67 (d, 1H, H4, J3,4 = 3.6 Hz), 7.20–7.24 (m, 1H, C6H5), 7.33–7.37
(m, 2H, C6H5), 7.66–7.69 (m, 2H, C6H5). 13C NMR d ppm: À3.25
Si-CH3, 12.95 C-CH3, 14.11 Si-CH2, 20.79 CH2-CH3, 21.42 C-CH2,
29.29 C-CH2, 54.00 N-CH2, 57.70 N-CH2, 105.12 C4, 121.92 C3, 124.05
C6H5, 127.27 C6H5, 128.59 C6H5, 131.21 C6H5, 157.91 C5, 159.42 C2.
29Si NMR d ppm: À9.25. GC-MS, m/z (%): 371 (M+, 8), 356 (M+ À Me,
3), 328 (4), 201 (8), 168 (10), 157 (61), 142 (100), 127 (7), 115 (7), 100
(16), 86 (6), 75 (8), 57 (6). HR-MS calcd for C23H38NO3Si (M+, 100)
372.2723, found 372.2721. Anal. Calcd for C23H37NOSi: C, 74.34;
H, 10.04; N 3.77. Found: C, 74.16; H, 9.89; N, 3.63.
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}azepane (18)
Compound 18 was prepared from compound
2 and N-
allylhexamethyleneimine by stirring and heating at 90 ꢀC for
1.5 h. Yield: 67.0% (brown oil). 1H NMR d ppm: 0.28 (s, 6H, Si-CH3),
0.71–0.75 (m, 2H, Si-CH2); 1.57–1.65 (m, 10H, C-CH2), 2.44–2.48
(m, 2H, N-CH2), 2.59–2.62 (m, 4H, N-CH2), 6.61 (d, 1H, H3,
J
3,4 = 3.0Hz), 6.67 (d, 1H, H4, J3,4 = 3.0 Hz), 7.20–7.24 (m, 1H, C6H5),
7.33–7.37 (m, 2H, C6H5), 7.67–7.69 (m, 2H, C6H5) 13C NMR d ppm:
À3.25 Si-CH3, 12.91 Si-CH2, 21.64 C-CH2, 27.03 C-CH2, 27.87 C-CH2,
55.54 N-CH2, 61.51 N-CH2, 105.12 C4, 121.94 C3, 124.03 C6H5,
127.26 C6H5, 128.58, C6H5 131.17 C6H5, 157.88 C5, 159.33 C2. 29Si
NMR d ppm: À9.25. GS-MS, m/z (%): 341 (M+, 6), 326 (M+ À Me, 4),
207 (5), 112 (100), 75 (7), 58 (11). HR-MS calcd for C21H32NOSi
(M+, 40) 342.2253, found 342.2271. Anal. Calcd for C21H31NOSi:
C, 73.85; H, 9.15; N 4.10. Found: C, 73.76; H, 9.04; N, 3.97.
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}pyrrolidine (15)
Compound 15 was prepared from compound 2 and N-
allylpyrrolidine by stirring and heating at 90 ꢀC for 1 h. Yield
1
65.1% (brown oil). H NMR d ppm: 0.29 (s, 6H, Si-CH3), 0.77–0.81
(m, 2H, Si-CH2); 1.56–1.64 (m, 2H, C-CH2), 1.73–1.78 (m, 4H,
C-CH2), 2.41–2.50 (m, 6H, N-CH2), 6.62 (d, 1H, H3, J3,4 = 3.2Hz),
6.67 (d, 1H, H4, J3,4 = 3.2 Hz), 7.22–7.25 (m, 1H, C6H5), 7.34–7.38
(m, 2H, C6H5), 7.67–7.69 (m, 2H, C6H5). 13C NMR d ppm: À3.33
Si-CH3, 13.15 Si-CH2, 23.29 C-CH2, 23.39 C-CH2, 54.18 N-CH2,
59.90 N-CH2, 105.12 C4, 121.97 C3, 124.04 C6H5, 127.27 C6H5,
128.58 C6H5, 131.17 C6H5, 157.90 C5, 159.25 C2. 29Si NMR d
ppm: À9.26. GS-MS, m/z (%): 313 (M+, 9), 298 (M+ À Me), 201
(15), 185 (8), 168 (22), 154 (5), 141 (36), 110 (40), 99 (17), 84
(100), 75 (32), 55 (30). HR-MS calcd for C19H28NOSi (M+, 10)
314.1940, found 314.1954. Anal. Calcd for C19H27NOSi: C, 72.79;
H, 8.68; N 4.47. Found: C, 72.54; H, 8.66; N, 4.31.
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}morpholine (19)
Compound 19 was prepared from compound 2 and N-
allylmorpholine by stirring and heating at 90 ꢀC for 1 h. Yield:
1
76.6% (yellow oil). H NMR d ppm: 0.29 (s, 6H, Si-CH3), 0.75–0.79
(m, 2H, Si-CH2); 1.54–1.62 (m, 2H, C-CH2), 2.31–2.45 (m, 6H,
N-CH2), 3.67–3.70 (m, 4H, O-CH2), 6,62 (d, 1H, H3, J3,4 = 3.2 Hz),
6.68 (d, 1H, H4, J3,4 = 3.2Hz), 7.22–7.26 (m, 1H, C6H5), 7.35–7.38
(m, 2H, C6H5), 7.67–7.70 (m, 2H, C6H5). 13C NMR d ppm: À3.32
Si-CH3, 12.87 Si-CH2, 20.81 C-CH2, 53.75 N-CH2, 62.30 N-CH2,
67.00 O-CH2, 105.12 C4, 122.04 C3, 124.02 C6H5, 127.33 C6H5,
128.60 C6H5, 131.12 C6H5, 157.94 C5, 159.08 C2. 29Si NMR d
ppm: À9.25. GS-MS, m/z (%): 329 (M+, 47), 314 (M+ À Me, 59),
300 (12), 256 (6), 242 (8), 224 (17), 201 (52), 185 (50), 185 (50),
171 (15), 157 (59), 145 (71), 135 (16), 127 (85), 115 (40), 100
(100), 86 (15), 75 (81), 68 (31), 56 (82). HRMS calcd for
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}piperidine (16)
Compound 16 was prepared from compound 2 and N-
allylpiperidine by stirring and heating at 90 ꢀC for 1 h. Yield
65.29% (light-brown oil). 1H NMR d ppm: 0.28 (s, 6H, Si-CH3),
0.71–0.76 (m, 2H, Si-CH2); 1.40–1.41 (m, 2H, C-CH2), 1.54–1.64 (6H,
m, C-CH2), 2.26–2.34 (m, 6H, N-CH2), 6.62 (d, 1H, H3, J3,4 = 3.2 Hz),
6.67 (d,1H, H4, J3,4 = 3.2Hz), 7.19–7.27 (m, 1H, C6H5), 7.34–7.38
(m, 2H, C6H5), 7.67–7.69 (m, 2H, C6H5). 13C NMR d ppm: À3.31
Si-CH3, 13.07 Si-CH2, 21.17 C-CH2, 24.51 C-CH2, 26.00 C-CH2,
54.65 N-CH2, 62.95 N-CH2, 105.10 C4, 121.94 C3, 124.03 C6H5,
127.25 C6H5, 128.56 C6H5, 131.16 C6H5, 157.88 C5, 159.25 C2. 29Si
NMR d ppm: À9.27. GS-MS, m/z (%): 327 (M+, 11), 312 (M+ À Me,
4), 155 (6), 145 (9), 124 (8), 98 (100), 75 (12), 55 (12). Calcd for
C20H30NOSi (M+, 20) 328.2097, found, 328.2112. Anal. Calcd for
C20H29NOSi: C, 73.34; H, 8.92; N 4.28. Found: C, 73.16; H, 8.96; N, 4.24.
C
19H28NO2Si (M+, 5), 330.1889, found 330.1916. Anal. Calcd
for C19H27NO2Si: C, 69.26; H, 8.26; N 4.25. Found: C, 69.09;
H, 8.26; N, 4.16.
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}-4-methylpiperazine (20)
Compound 20 was prepared from compound 2 and N-allyl-4-
methylpiperazine by stirring and heating at 90 ꢀC for 1 h. Yield:
1
68.4% (yellow oil). H NMR d ppm: 0.28 (s, 6H, Si-CH3), 0.73–0.78
(m, 2H, Si-CH2); 1.54–1.65 (m, 2H, C-CH2), 2.26 (s, 3H, CH3),
2.32–2.57 (m, 8H, N-CH2), 6.62 (d, 1H, H3, J3,4 = 3.2 Hz), 6.68
(d, 1H, H4, J3,4 = 3.2 Hz), 7.22–7.25 (m, 1H, C6H5), 7.34–7.38
(m, 2H, C6H5), 7.67–7.69 (m, 2H, C6H5). 13C NMR d ppm: - 3.33
Si-CH3, 12.93 Si-CH2, 21.13 C-CH2, 46.05 N-CH3, 53.21 N-CH2,
55.13 N-CH2, 61.95 N-CH2, 105.10 C4, 121.99 C3, 124.02 C6H5,
127.27 C6H5, 128.57 C6H5, 131.13 C6H5, 157.90 C5, 159.12 C2.
29Si NMR d ppm: À9.29. GS-MS, m/z (%): 342 (M+, 16), 327 (M+ À Me,
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}-2-methylpiperidine (17)
Compound 17 was prepared from compound 2 and N-allyl-2-
methylpiperidine by stirring and heating at 90 ꢀC for 1 h. Yield:
Appl. Organometal. Chem. 2013, 27, 406–411
Copyright © 2013 John Wiley & Sons, Ltd.
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L. Ignatovich et al.
4), 207 (6), 157 (5), 128 (7), 113 (100), 98 (5), 77 (5), 70 (40). HR-MS
calcd for C20H31N2OSi (M+, 10) 343.2206, found 343.2225. Anal.
Calcd for C20H30N2OSi: C, 70.13; H, 8.23; N 8.18. Found: C, 69.99; H,
8.39; N, 8.01.
In order to reveal the effect of a heterocyclic amino group and an
organic substituent at the furan ring in the furylsilylpropylamines
3–21 on their antitumor activity, we studied their cytotoxicity
in vitro on two cell tumor lines, viz. HT-1080 (human fibrosarcoma)
and MG-22A (mouse hepatoma). In comparison, we studied the
cytotoxicity (IC50) of these compounds towards normal NIH 3 T3
cells (normal mouse embryonic fibroblasts – Swiss Albino mice)
and also their toxicity (LD50). The experimental evaluation of cyto-
toxic properties is presented in Table 1. The investigations showed
that, regardless of the structure of the amine (R1), all of the com-
pounds studied (3–21) possessed moderate toxicity (lethal doses
for them are in the range 102–756 mg kgÀ1, with the exception of
compounds 14 and 17). The amines 14 and 17 showed high
cytotoxic activity in cancer cells accompanied by the highest
cytotoxic activity on normal cells 3 T3 (IC50 0.3 mg mlÀ1). It is inter-
esting to note that all of the derivatives with a phenyl substituent
in position 5 of the furan ring (compounds 13–21) were more
active than compounds with a diethoxymethyl substituent in posi-
tion 5 of the furan ring (compounds 3–12) (Table 1). However,
some amino derivatives of diethoxymethylfuran (3, 7, 11) exhibit
1-{3-[Dimethyl(5-phenylfuran-2-yl)silyl]propyl}-4-phenylpiperazine (21)
Compound 21 was prepared from compound 2 and N-allyl-4-
phenylpiperazine by stirring and heating at 90 ꢀC for 2.5 h. Yield:
71.3% (light-brown). 1H NMR d ppm: 0.29 (s, 6H, Si-CH3), 0.76–0.80
(m, 2H, Si-CH2); 1.58–1.66 (m, 2H, C-CH2), 2.37–2.41 (m, 2H,
N-CH2), 2.55–2.58 (m, 4H, N-CH2), 3.15–3.18 (m, 4H, N-CH2), 6.62
(d, 1H, H3, J3,4 = 3.2Hz), 6.68 (d, 1H, H4, J3,4 = 3.2Hz), 6.81–6.90
(m, 3H, C6H5), 7.21–7.25 (m, 3H, C6H5), 7.34–7.38 (m, 2H, C6H5),
7.67–7.69 (m, 2H, C6H5). 13C NMR d ppm: - 3.30 Si-CH3, 12.94
Si-CH2, 21.09 C-CH2, 49.07 N-CH2, 53.23 N-CH2, 61.90 N-CH2,
105.15 C4, 116.00 C6H5, 119.59 C3, 122.07 C6H5, 124.04 C6H5,
127.32 C6H5, 128.61 C6H5, 129.06 C6H5, 131.13 C6H5, 151.34
C6H5, 157.95 C5, 159.10 C2. 29Si NMR d ppm: À9.20. GS-MS, m/z
(%): 404 (M+, 30), 389 (M+ À Me, 5), 327 (5), 259 (5), 201 (9), 175
(100), 157 (9), 145 (9), 132 (19), 115 (6), 104 (14), 70 (25), 56 (9).
high cytotoxic activity on MG-22A cancer cells (IC50 2–4 mg mlÀ1
)
HR-MS calcd for
C
25H33N2OSi (M+, 20) 405.2362, found
and at the same time they were much less cytotoxic on normal
fibroblasts (IC50 20–67 mg mlÀ1). Silylpropylamino derivatives of
diethoxymethylfuran 3–12 have a certain cytoselectivity: com-
pounds of this type exhibited high cytotoxicity to MG-22 tumor cell
lines (compounds 9 and 12 are an exception) and at the same time
they were less toxic to HT-1080. It should be noted that compounds
with the phenyl substituent in position 5 of the furan ring generally
405.2343. Anal. Calcd for C25H32N2OSi: C, 74.21; H, 7.97; N 6.92.
Found: C, 74.06; H, 8.09; N, 7.01.
Results and Discussion
In a continuation of our studies we have examined hydrosilylation
of a series of allylamines with dimethyl(2-furyl)silane containing a
diethylacetal group at C-5 of the furan ring. After removal of
the protective group new synthesized compounds can serve as
synthons in the synthesis of new biologically active compounds.
The choice of aromatic substituent for our investigations was asso-
ciated with the fact that numerous phenyl-substituted derivatives
had been studied as anticancer compounds and a lot of them
had been already used for treatment of cancer.[7–10] The starting
5-dimethylsilylfurfural diethyl acetal (1) has been prepared by
known methods.[3] The 2-dimethylsilyl-5-phenylfuran (2) has been
obtained by using the organolithium method. They were used for
the hydrosilylation of heterocyclic allylamines in the presence of
Speier’s catalyst (Scheme 1). The hydrosilylation reaction of all stud-
ied allyamines by hydrosilanes 1 and 2 occurred smoothly over
1–2.5 h (in some cases an exothermic reaction occurred immedi-
ately; in other cases, it required heating for 15–150 min) at the
presence a drop of Speier’s catalyst. The reaction afforded a
series of silylamines 3–21 in good or moderate yield.
Table 1. Cytotoxic activity (IC50) of compounds 3–21
Compound
IC50 (mg mlÀ1
)
LD50
(mg kgÀ1
)
HT-1080
MG-22A
NIH3T3
NR
CV MTT NO
CV MTT NO
3
33 34 200
2
3
3
3
3
2
3
4
100
100
100
200
100
133
100
100
150
150
250
250
200
150
200
250
150
200
75
33
17
44
27
20
10
72
32
67
10
5
512
756
577
495
405
331
747
520
737
345
221
74
4
6
10 100
5
20 30 150
15 30 200
17 27 100
10
10
3
6
7
8
4
10 200
3
9
33 32 150
21 24 100
32 30 150
13 22
10
11
12
13
14
15
16
17
18
19
20
21
2
3
3
2
1
1
1
1
1
1
1
8
6
4
3
2
1
1
1
2
1
2
3
8
4
1
3
3
3
1
1
3
3
4
4
3
3
2
1
2
1
3
3
4
150
150
300
200
150
200
150
200
200
150
0.3
4
188
164
68
3
0.3
11
60
6
102
659
240
283
6
IC50, the concentration providing 50% cell death; LD50, the
calculated values of expected toxicity; CV, crystal violet (action
on the cell membrane); MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl-2H-tetrazolium bromide (influence on the activity of
mitochondrial enzymes in the cell); NR, neutral red; NO, degree
of generation of the NO radical determined and calculated by
the method of Fast et al.[5]
Scheme
organylfurans.
1. Synthesis
of
2-[(3-aminopropyl)dimethylsilyl]-5-
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 406–411

New 2-[(3-aminopropyl)dimethylsilyl]-5-organylfurans
have more pronounced cytotoxic activity on tumor cell lines
compared to the analogues with Et3Si group[2] and Et3Ge
group in the furan ring.[1] Morpholino derivative 19 is the more
promising compound among the studied amines: moderate toxic-
This work has been carried out with the support of the Latvian
Council of Science (projects 09.1556, 10.0030, 225/2012).
ity (LD50 659 mgkgÀ1), high cytotoxicity on both cancer cell lines References
(IC50 1–3 mg mlÀ1) and low cytotoxicity on normal fibroblasts
[1] L. Ignatovich, V. Muravenko, I. Shestakova, I. Domrachova, J. Popelis,
(IC50 60mg mlÀ1).
E. Lukevics, Appl. Organomet. Chem. 2010, 24, 158.
[2] L. Ignatovich, V. Romanov, I. Shestakova, I. Domrachova, J. Popelis,
E. Lukevics, Chem. Heterocycl. Comp. 2009, 45, 1441.
Conclusions
[3] E. Lukevics, L. Demicheva, N. Erchak, S. Germane, Appl. Organomet.
Chem. 1993, 7, 543.
[4] R. I. Freshney, Culture of Animal Cells: A Manual of Basic Technique,
Wiley-Liss, New York, 1994, pp. 29.
Our investigations have shown that by variations of the substitu-
ents (organosilicon, organogermanium or organic) at position 5
of the furan ring in 2,5-substituted furylsilylpropylamines we
can achieve a high cytotoxicity against cancer cells and low
toxicity and cytotoxicity on normal fibroblasts. The effect of the
nature of the amine on the cytotoxic activity is not so large in
the studied compounds.
[5] D. I. Fast, R. C. Lunch, R. W. Leu, J. Leucocyt. Biol. 1992, 52, 255.
[6] Report of the International Workshop on in vitro Methods for
Assessing Acute Systemic Toxicity, NIH Publ. No. 01-4499 (2001),
p. 12. Available: http://www.epa.gov/hpv/pubs/general/nih2001b.
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Copyright © 2013 John Wiley & Sons, Ltd.
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