DOI: 10.3109/14756366.2015.1031126
Naphthalene-based thiosemicarbazone derivatives
3
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.18 (CH3), 55.20
Anal. Calcd. for C20H16N4S: C, 69.74; H, 4.68; N, 16.27.
(CH3), 113.52 (CH), 113.72 (CH), 113.78 (CH), 123.25 (CH), Found: C, 69.75; H, 4.69; N, 16.28.
125.39 (CH), 125.95 (C), 126.04 (CH), 126.26 (CH), 126.76
(CH), 127.99 (CH), 128.45 (CH), 129.96 (CH), 130.51 (C), 4-(Naphthalen-1-yl)-1-[1-(4-trifluoromethoxyphenyl)
133.68 (C), 135.89 (C), 148.63 (C), 160.35 (C), 178.59 (C).
MS (ESI) (m/z): [M + 1]+ 350.
Anal. Calcd. for C20H19N3OS: C, 68.74; H, 5.48; N, 12.02.
Found: C, 68.75; H, 5.49; N, 12.03.
ethylidene)thiosemicarbazide (12)
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.34 and 2.37 (3H, 2 s,
CH3), 7.36–7.41 (4H, m, aromatic), 7.48–7.49 (2H, m, aromatic),
7.81–7.91 (2H, m, aromatic), 8.09–8.10 (2H, m, aromatic), 8.18–
8.22 (1H, m, aromatic), 10.58 (1H, s, N–H), 10.95 (1H, s, N–H).
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.22 (CH3),
118.74 (CH), 120.50 (CH), 120.71 (CH), 121.29 (CH), 123.84
4-(Naphthalen-1-yl)-1-[1-(4-methylphenyl)ethylidene)
thiosemicarbazide (8)
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.32–2.34 (3H, m, (CH), 124.57 (C), 125.28 (CH), 125.88 (CH), 126.61 (CH),
CH3), 2.40 (3H, s, CH3), 7.19–7.26 (2H, m, aromatic), 7.49–7.58 127.61 (CH), 128.69 (2CH), 128.95 (C), 133.69 (CF3), 136.70
(4H, m, aromatic), 7.82–8.02 (5H, m, aromatic), 10.31 (1H, s, (2C), 147.82 (C), 149.03 (C), 176.79 (C).
N–H), 10.66 (1H, s, N–H).
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.24 (CH3), 20.87
MS (ESI) (m/z): [M + 1]+ 404.
Anal. Calcd. for C20H16F3N3OS: C, 59.55; H, 4.00; N, 10.42.
(CH3), 123.26 (CH), 125.41 (CH), 125.96 (CH), 126.05 (C), Found: C, 59.56; H, 4.01; N, 10.43.
126.29 (CH), 126.82 (2CH), 128.00 (CH), 128.79 (2CH), 130.51
(CH), 133.68 (CH), 134.77 (C), 135.88 (C), 138.98 (2C), 148.73 4-(Naphthalen-1-yl)-1-[1-(4-(4-morpholinyl)phenyl)ethylidene)
(C), 178.73 (C).
MS (ESI) (m/z): [M + 1]+ 334.
Anal. Calcd. for C20H19N3S: C, 72.04; H, 5.74; N, 12.60.
Found: C, 72.05; H, 5.75; N, 12.61.
thiosemicarbazide (13)
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.28 (3H, s, CH3), 3.17
(4H, s, morpholine), 3.72 (4H, s, morpholine), 6.91–6.92 (3H, m,
aromatic), 7.50–7.56 (6H, m, aromatic), 8.26–8.30 (2H, m,
aromatic), 10.25 (1H, s, N–H), 10.56 (1H, s, N–H).
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.02 (CH3), 47.63
(2CH2), 65.95 (2CH2), 113.79 (CH), 113.88 (2CH), 123.19 (CH),
4-(Naphthalen-1-yl)-1-[1-(4-trifluoromethylphenyl)
ethylidene)thiosemicarbazide (9)
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.37 (3H, s, CH3), 125.39 (CH), 125.95 (C), 126.04 (CH), 126.16 (CH), 126.70 (C),
7.47–7.61 (6H, m, aromatic), 7.71–7.78 (4H, m, aromatic), 7.90– 127.72 (CH), 127.92 (CH), 128.01 (CH), 130.46 (CH), 133.67
7.91 (1H, m, aromatic), 10.44 (1H, s, N–H), 10.86 (1H, s, N–H). (C), 135.86 (C), 149.03 (C), 151.75 (C), 178.31 (C).
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.30 (CH3),
MS (ESI) (m/z): [M + 1]+ 405.
122.86 (CH), 123.31 (CH), 124.91 (CH), 125.43 (C), 125.57 (C),
Anal. Calcd. for C23H24N4OS: C, 68.29; H, 5.98; N, 13.85.
126.01 (CH), 126.10 (CH), 126.45 (CH), 126.63 (CH), 127.60 Found: C, 68.28; H, 5.97; N, 13.86.
(2CH), 128.00 (CH), 130.53 (CH), 133.69 (C), 135.83 (C), 141.40
(C), 141.51 (C), 146.86 (C), 179.13 (C).
MS (ESI) (m/z): [M + 1]+ 388.
4-(Naphthalen-1-yl)-1-[1-(4-(1-piperidinyl)phenyl)ethylidene)
thiosemicarbazide (14)
Anal. Calcd. for C20H16F3N3S: C, 62.00; H, 4.16; N, 10.85.
Found: C, 62.01; H, 4.17; N, 10.86.
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 1.54–1.58 (6H, m,
piperidine), 2.36 (3H, s, CH3), 3.20–3.31 (4H, m, piperidine),
6.81–6.90 (6H, m, aromatic), 7.49–7.63 (5H, m, aromatic), 10.22
(1H, s, N–H), 10.55 (1H, s, N–H).
4-(Naphthalen-1-yl)-1-[1-(4-methylsulphonylphenyl)
ethylidene)thiosemicarbazide (10)
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 13.97 (CH3), 23.91
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.47 (3H, s, CH3), 3.23 (CH2), 24.94 (2CH2), 48.44 (CH2), 48.59 (CH2), 114.55 (CH),
(3H, s, CH3), 7.51–7.58 (6H, m, aromatic), 7.89–7.91 (4H, m, 114.21 (2CH), 123.14 (CH), 125.37 (CH), 125.93 (C), 126.02
aromatic), 8.15–8.16 (1H, m, aromatic), 10.46 (1H, s, N–H), (CH), 126.59 (CH), 126.64 (C), 127.59 (CH), 127.93 (CH),
10.88 (1H, s, N–H).
128.00 (CH), 130.41 (CH), 133.66 (C), 135.83 (C), 149.17 (C),
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.35 (CH3), 43.47 151.98 (C), 178.19 (C).
(CH3), 123.31 (CH), 125.45 (CH), 126.04 (CH), 126.13 (C),
126.48 (CH), 126.74 (CH), 127.18 (CH), 127.45 (CH), 127.68
MS (ESI) (m/z): [M + 1]+ 403.
Anal. Calcd. for C24H26N4S: C, 66.22; H, 6.79; N, 17.16
(CH), 128.02 (CH), 130.53 (CH), 133.70 (CH), 135.82 (C), Found: C, 66.23; H, 6.78; N, 17.17.
140.80 (C), 141.57 (C), 142.37 (C), 146.67 (C), 179.14 (C).
MS (ESI) (m/z): [M + 1]+ 398.
Cytotoxicity
Anal. Calcd. for C20H16F3N3S: C, 60.43; H, 4.82; N, 10.57.
Found: C, 60.44; H, 4.83; N, 10.58.
Drug preparation
Compounds 1–14 were dissolved in dimethyl sulfoxide (DMSO,
Sigma, St Louis, MO) and diluted further with Dulbecco’s
modified Eagle’s medium (DMEM, Sigma) to obtain the required
final concentrations (5, 10, 25, 50 and 75 mM).
4-(Naphthalen-1-yl)-1-[1-(4-cyanophenyl)ethylidene)
thiosemicarbazide (11)
1H NMR (500 MHz) (DMSO-d6) ꢀ (ppm): 2.44 (3H, s, CH3),
7.49–7.58 (4H, m, aromatic), 7.83–7.99 (5H, m, aromatic), 8.26–
8.30 (2H, m, aromatic), 10.47 (1H, s, N–H), 10.87 (1H, s, N–H).
Cell culture
13C NMR (100 MHz) (DMSO-d6) ꢀ (ppm): 14.10 (CH3), Human prostate cancer cell line (LNCaP) was obtained from the
111.31 (CH), 111.36 (C), 118.83 (C), 123.33 (CH), 125.45 (CH), American Type Culture Collection and grown in complete
126.07 (C), 126.11 (CH), 126.48 (CH), 127.01 (CH), 127.61 medium containing DMEM supplemented with 10% fetal calf
(CH), 127.98 (CH), 130.55 (CH), 132.04 (2CH), 133.69 (C), serum (Sigma) and 1% penicillin (10 000 unit)–streptomycin
135.86 (C), 141.87 (C), 146.46 (C), 179.14 (C).
MS (ESI) (m/z): [M + 1]+ 345.
(10 mg/mL) solution (Sigma) in a humidified atmosphere of 95%