Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay
Abstract
:1. Introduction
2. Results and Discussion
3. Experimental Section
3.1. Chemicals
3.2. Preparation of Compounds 1–6
3.3. Metabolic Activation System (S9 Mixture)
3.4. Bacterial Strains
3.5. Mutagenicity Assay
4. Conclusions
Acknowledgments
References and Notes
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Revertants/plate in Salmonella typhimurium strains | |||||
---|---|---|---|---|---|
Compounds | Concentration μmol/plate | TA100 | TA102 | ||
+S9 | −S9 | +S9 | −S9 | ||
0 | 129.3 ± 8.1 | 143 ± 4.8 | 372.3 ± 20.5 | 370 ±17.2 | |
29.25 | 178.33 ± 15.1* (1.4) | 149 ± 8.9 (1.0) | 399 ± 31 (1.1) | 411.3 ± 9.8 (1.1) | |
58.5 | 240 ± 3** (1.8) | 159 ± 11 (1.1) | 484.6 ± 36 (1.3) | 498 ± 15.3 (1.3) | |
117 | 220.7 ± 17.8** (1.7) | 268.7 ± 13.5* (1.9) | 563.3 ± 22** (1.5) | 602 ± 8.7* (1.6) | |
234 | 276 ± 27.7** (2.1) | 345 ± 21.2** (2.4) | 764.3 ± 20** (2.0) | 799.6 ± 12** (2.2) | |
468 | 315.3 ± 16.1** (2.4) | 358.6 ± 5.5** (2.5) | 593 ± 23** (1.6) | 550 ± 7.5** (1.5) | |
0 | 129.3 ± 8.1 | 136.7 ± 2.4 | 213.5 ± 15.5 | 197.33 ± 16.01 | |
0.007 | 126.3 ± 8.1 (1.0) | 140.5 ± 17 (1.0) | 288 ± 11.3 (1.3) | 249.7 ± 12 (1.2) | |
0.014 | 133.3 ± 11 (1.0) | 161.7 ± 11 (1.2) | 320.8 ± 17* (1.5) | 263.7 ± 15 (1.3) | |
0.028 | 140.3 ± 2 (1.1) | 192.7 ± 3.06 (1.4) | 385 ± 21.8** (1.8) | 261.3 ± 20 (1.3) | |
0.056 | 154 ± 14.2 (1.2) | 234 ± 39.5** (1.7) | 499 ± 8.9** (2.3) | 153 ± 21 (0.8) | |
0.112 | 155 ± 5.9 (1.2) | 335 ± 15.7**(2.4) | 351.2 ± 12*(1.6) | 141 ± 18 (0.7) | |
0 | 104 ± 7.4 | 115 ± 13.2 | 219 ± 8.9 | 323 ± 10.2 | |
0.01 | 335 ± 10.8**(3.2) | 171 ± 38.9* (1.5) | 249 ± 11.7 (1.1) | 394 ± 30 (1.2) | |
0.021 | 354 ± 6.9**(3.4) | 200 ± 13.3* (1.7) | 269 ± 10.6 (1.2) | 411 ± 24 (1.3) | |
0.042 | 397 ± 25.9** (3.8) | 223 ± 15.04* (1.9) | 239 ± 22.5 (1.1) | 452 ± 35.4 (1.4) | |
0.085 | 416 ± 15.2** (4.0) | 226 ± 20.2* (2.0) | 247 ± 21.4 (1.1) | 468 ± 23 (1.4) | |
0.170 | 261 ± 11** (2.5) | 165 ± 11.1* (1.4) | 205 ± 32 (0.9) | 518 ± 14** (1.6) | |
0 | 129 ± 8.1 | 179 ± 8.72 | 222 ± 12.5 | 254.7 ± 14.6 | |
0.224 | 146 ± 5 (1.1) | 216.7 ± 10.2 (1.2) | 272 ± 26 (1.2) | 281 ± 25 (1.1) | |
0.488 | 153 ± 13.1 (1.2) | 234.5 ± 24.6 (1.3) | 378 ± 6.1* (1.7) | 286 ± 4.2 (1.1) | |
0.896 | 163 ± 9.3(1.2) | 266.3 ± 8.4* (1.5) | 399.3 ± 12* (1.8) | 303 ± 9.2 (1.2) | |
1.8 | 165 ± 12.5 (1.3) | 294.5 ± 5.3* (1.6) | 405 ± 11* (1.8) | 395.7 ± 9** (1.5) | |
3.58 | 155 ± 8.2 (1.3) | 323.7 ± 10.2* (1.8) | 431 ±17.9* (1.9) | 410.3 ± 9.7* (1.6) | |
0 | 129.3 ± 8.14 | 126.7 ± 12.1 | 312.3 ± 27.5 | 197.3 ± 16.1 | |
0.98 | 160 ± 12.4 (1.2) | 146.3 ± 5.1 (1.1) | 323 ± 5.54 (1.0) | 222 ± 12 (1.1) | |
1.96 | 175.7 ± 2 (1.4) | 172.7 ± 7.8 (1.4) | 385 ± 33.1 (1.2) | 241 ± 13 (1.2) | |
3.92 | 194.2 ± 15 (1.5) | 190 ± 11.3* (1.5) | 423.7 ± 22 (1.3) | 251 ± 19.2(1.3) | |
7.85 | 206 ± 13.6** (1.6) | 208 ± 12.5* (1.6) | 443 ± 14.4 (1.4) | 232 ± 13.1(1.2) | |
15.7 | 354 ± 6.5* (2.7) | 155 ± 2.8 (1.22) | 295 ± 4.9 (0.9) | 210 ± 17 (1.1) | |
0 | 129.3 ± 8.1 | 179 ± 8.7 | 372.3 ± 27.5 | 260.1 ± 11.6 | |
0.224 | 157 ± 13 (1.2) | 220 ± 18 (1.2) | 385.7 ± 13 (1.0) | 340.3 ± 9.7 (1.3) | |
0.488 | 184.7 ± 16* (1.4) | 239 ± 11.5 (1.3) | 427.3 ± 5 (1.1) | 373.5 ± 21 (1.4) | |
0.896 | 192.7 ± 16* (1.5) | 261 ± 10.2 (1.4) | 436.7 ± 21 (1.2) | 391.2 ± 6.3* (1.5) | |
1.8 | 216.7 ± 18** (1.7) | 303,8 ± 17* (1.7) | 390.3 ± 9.3(1.0) | 486.8 ± 20** (1.9) | |
3.58 | 263 ± 12.3** (2.0) | 349 ± 5.6** (1.9) | 350 ± 6 (0.9) | 420 ± 8.6* (1.6) | |
0 | 129.3 ± 8.1 | 116.7 ± 12.4 | 295.3 ± 28 | 197.3 ± 16.1 | |
0.12 | 363 ± 25.2** (2.8) | 121.5 ± 14 (1.0) | 335.3 ± 11 (1.1) | 245 ± 6.9 (1.2) | |
0.25 | 478.7 ± 4.22 **(3.7) | 135.3 ± 12 (1.1) | 372.3 ± 27.5 (1.3) | 262 ± 19.1 (1.3) | |
0.5 | 628 ± 40.8** (4.9) | 138.3 ± 13 (1.2) | 406 ± 14.1 (1.4) | 286.7 ± 18 (1.4) | |
1 | 739 ± 25.4** (5.7) | 153.3 ± 5 (1.3) | 465 ± 10.6* (1.6) | 305.7 ± 10* (1.5) | |
2 | 750 ± 13.6** (5.8) | 177 ± 23.6* (1.5) | 447 ± 19.8* (1.5) | 201 ± 4.7 (1.0) | |
Positive control*** | - | 2545 ± 73.6 | 2231 ± 66.9 | 812 ± 26.1 | 881 ± 56.1 |
Compounds | TA100 | TA102 | ||
---|---|---|---|---|
(+S9) | (−S9) | (+S9) | (−S9) | |
HU | 1.8 | 1.1 | 1.7 | 2.0 |
1 | - | 1795 | 4803 | - |
2 | 1041 | 4025 | - | - |
3 | - | - | - | - |
4 | 13.6 | - | - | - |
5 | 31 | - | - | - |
6 | 1393 | - | - | - |
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Dos Santos, J.L.; Varanda, E.A.; Lima, L.M.; Chin, C.M. Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay. Int. J. Mol. Sci. 2010, 11, 779-788. https://doi.org/10.3390/ijms11020779
Dos Santos JL, Varanda EA, Lima LM, Chin CM. Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay. International Journal of Molecular Sciences. 2010; 11(2):779-788. https://doi.org/10.3390/ijms11020779
Chicago/Turabian StyleDos Santos, Jean Leandro, Eliana A. Varanda, Lídia Moreira Lima, and Chung Man Chin. 2010. "Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay" International Journal of Molecular Sciences 11, no. 2: 779-788. https://doi.org/10.3390/ijms11020779