BULETINUL ИЗВЕСТИЯ JOURNAL

More documents

Recommendations

Info

Buletinul AŞM. Ştiinţele vieţii. Nr. 3(318) 2012 Fiziologia şi Samocreatologia to a hot (65°C) solution of 1.95 g (10 mmol) of 2 in 4 mL ethanol. 2 to 4 drops of glacial acetic acid was added as a catalyst. The resulting mixture was refl uxed at 75°C for 2h. Then, the solution was allowed to reach ambient temperature and cooled to 0°C overnight. The crude product was fi ltered, dried and recrystallized from ethanol- DMF solvent mixture. Yield, 2.46 g (85%), m.p. 220°C. 1 H-NMR (DMSO-d 6 ) δ: 2.19 (s, 3H, o-CH 3 ); 2.30 (s, 3H, p-CH 3 ); 7.02, 7.08, 7.15 (m, 3H, phenyl); 8.17 (s, 1H, azomethine); 7.59, 7.84, 7.96 (m, 3H, thiophenyl); 9.81 (s, 1H, C Ph –NH); 11.69 (s, 1H, NH–N=). 13 C-NMR (DMSO-d 6 ) δ: 18.23 (o-CH 3 ); 21.11 (p-CH 3 ); 126.89, 131.07, 135.54, 135.97, 136.20, 138.07 (phenyl); 126.24 (azomethine); 127.54, 128.49, 128.96 (thiophenyl), 177.29 (C=S). N -( 2 , 4 - d i m e t h y l p h e n y l) - 2 -( q u i n o l i n e - 2 - y l m e t h y l e n e) hydrazinecarbothioamide (7): 1.73 g (11 mmol) of 2-formylquinoline was added to a hot (65°C) solution of 1.95 g (10 mmol) of 2 in 4 mL ethanol. 2 to 4 drops of glacial acetic acid was added as a catalyst. The resulting mixture was refl uxed at 75°C for 2h. Then, the solution was allowed to reach ambient temperature and cooled to 0°C overnight. The crude product was fi ltered, dried and recrystallized from ethanol-DMF solvent mixture. Yield, 2.87 g (86%), m.p. 208°C. 1 H-NMR (DMSO-d 6 ) δ: 2.22 (s, 3H, o-CH 3 ); 2.31 (s, 3H, p-CH 3 ); 7.05, 7.11, 7.14 (m, 3H, phenyl); 8.34 (s, 1H, azomethine); 7.63, 7.78, 7.98, 8.04, 8.37, 8.63 (m, 6H, quinolyl); 10.22 (s, 1H, C Ph –NH); 12.15 (s, 1H, NH–N=). 13 C-NMR (DMSO-d 6 ) δ: 18.24 (o-CH 3 ); 21.12 (p-CH 3 ); 118.87, 127.04, 130.38, 135.85, 136.54, 136.68 (phenyl); 143.08 (azomethine); 119.6, 127.0, 128.3, 128.9, 129.9, 130.9, 136.5, 148.5, 149.3 (quinolyl), 177.89 (C=S) N-(2,4-dimethylphenyl)-2-(2-hydroxybenzylidene)hydrazinecarbothioamide (8): 1.23 g (11 mmol) of salicylaldehyde was added to a hot (65°C) solution of 1.95 g (10 mmol) of 2 in 4 mL ethanol. 2 to 4 drops of glacial acetic acid was added as a catalyst. The resulting mixture was refl uxed at 75°C for 2h. Then, the solution was allowed to reach ambient temperature and cooled to 0°C overnight. The crude product was fi ltered, dried and recrystallised from ethanol-DMF solvent mixture. Yield, 2.66 g (89%), m.p. 187-188°C. 1 H-NMR (DMSO-d 6 ) δ: 2.18 (s, 3H, o-CH 3 ); 2.29 (s, 3H, p-CH 3 ); 7.01, 7.07, 7.15 (m, 3H, phenyl); 8.47 (s, 1H, azomethine); 6.82, 6.88, 7.23, 8.07 (m, 4H, hydroxyphenyl); 9.82 (s, 1H, OH); 9.95 (s, 1H, C Ph –NH); 11.69 (s, 1H, NH–N=). 13 C-NMR (DMSO-d 6 ) δ: 18.18 ( o-CH 3 ); 21.06 ( p-CH 3 ); 119.69, 126.84, 131.09, 133.62, 135.36, 136.00 (phenyl); 140.42 (azomethine); 117.82, 118.58, 121.43, 127.52, 136.18, 156.99 (hydroxyphenyl), 177.31 (C=S). Results and discussion Antileukaemia activity. Six of the synthesized compounds were tested as inhibitors of HL-60 cells proliferation. These human promyelocytic leukaemia cells were incubated for three days in the presence of synthetic compounds and the number of viable cells was measured using the MTS assay (Scheme 2). The results are expressed as the percentage of cell growth inhibition at three concentrations (Table 1). As it can be concluded from the data above, N-(2,4dimethylphenyl) hydrazinecarbothioamide 2 has a pretty low antiproliferative activity. Thereby, at the concentration of 0.1 μM 2 shows its highest activity, almost equal to that of Doxorubicin at the same concentration. Thiosemicarbazones 4 and 5 do not inhibit cell proliferation at any concentration. 63
Buletinul AŞM. Ştiinţele vieţii. Nr. 3(318) 2012 The highest antiproliferative activity shows 6 in 10 μM solution and 8 in 10 μM and 1 μM solutions. Table 1. Antiproliferative activity of compounds 2-8 against human myeloid leukaemia (HL-60) cancer cells Compound Inhibition of cell proliferation (%) Fiziologia şi Samocreatologia 10 μM 1 μM 0.1 μM 2 8.5 10.4 16 4 0 0 0 5 0 0.4 0 6 90.3 0 0 7 0.2 6.6 0 8 89.9 96.5 9.7 Doxorubicin 99 98 15 Therefore, it can be inferred that the antiproliferative activity of the compounds 4-8 is infl uenced by the nature of R and it grows in the following order: pyridine-3-yl ≤ pyridine-4-yl < quinoline-2-yl < thiophene-3-yl < 2-hydroxyphenyl. When comparing the activity of the thiosemicarbazide 2 to the activities of thiosemicarbazones 4-8, it becomes conspicuous that the replacing of hydrogen atoms from NH 2 group with arilmethylene group (aril = carbocyclic or heterocyclic aromatic rest) leads either to decrease or signifi cant increase of the antiproliferative activity. When the aromatic rest from arilmethylene group is pyridine-3-yl, pyridine-4-yl or quinoline-2-yl the antiproliferative activity is brought down to zero. On the contrary, when the aril rest is a thiophene-3-yl or a 2-hydroxyphenyl, the activities rise up to values comparable to those of the currently used in medical practice Doxorubicin. Hence, thiosemicarbazones 6 and 8 are of interest for further studies as potential alternatives to traditional antileukaemia medicines. Scheme 2. The effect on HL- 60 cancer cells proliferation X-ray diffraction. N-(2,4-dimethylphenyl) hydrazinecarbothioamide crystallises in a P1 21/n 1 (14) monoclinic space group. The parameters of elementary cell are: a = 11.5215(5) Å, b = 7.5680(5) Å, c = 11.7534(7) Å; β = 99.24(1)°; V = 1011.54(89) Å 3 . As the length of the C–S bond is 1.696 Å, value closer to the theoretical C–S 64
Page 1 and 2:
Buletinul AŞM. Ştiinţele vieţii
Page 3 and 4:
Page 5 and 6:
Page 7 and 8:
Page 9 and 10:
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26: Buletinul AŞM. Ştiinţele vieţii
Page 75: Buletinul AŞM. Ştiinţele vieţii
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215:
show all

BULETINUL ИЗВЕСТИЯ JOURNAL

Create successful ePaper yourself

Delete template?

Save as template?