Thiogenistein—Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products
Abstract
:1. Introduction
2. Results and Discussion
2.1. ABTS Radical ScavengingAssay
2.2. H2DCF-DA ROS Detection Assay
2.3. In Vitro Study–Cell Viability, Cytotoxicity
Antitumor Activity–Breast Cancer
2.4. Antioxidant Chemistry–Oxidation of TGE by Potential and With Hydrogen Peroxide
2.5. Description of Qualitative Changes Observed in the IR-ATR Spectra during the Oxidation of the TGE Monolayer on the Au Electrode
Vibrational Studies on Oxidative Monolayers–Simulation of Active Substance Immobilization on the Surface of Biological Membranes
2.6. Molecular Modeling and the Quantum Mechanical Density Functional Calculations
3. Materials and Methods
3.1. Materials
3.2. Antioxidant Study
3.2.1. ABTS Radical Scavenging Assay
3.2.2. H2DCF-DA ROS Detection Assay
3.3. In Vitro Study–Cell Viability, Cytotoxicity
3.4. Electrochemical Measurements
3.5. MS Spectrometry
3.6. IR Measurements
3.7. Quantum Mechanical Modeling
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Product Mass, Characteristic Ions m/z, (rel. int., % for EPI) | No. Oxidation Product/Intensity | Proposed Metabolic Reaction-Suggested Reactions |
---|---|---|
TGE [M-H]− = 387 Da; DP (−80), CE (−40) 0V, m/z (EPI−) 387: 369(1); 343(1); 327(1); 313(1); 299(1); 295(1); 286(1); 269(100); 268(13); 255(1); 241(1); 225(1); 224(1); 211(1); 201(1); 199(1); 196(1); 181(1); 157(1) Electrode: BDD; pulse 5: pulse of 1 s/+2.5 V + pulse of 0.5 s/−0.3 V m/z: EPI− | ||
402: 384(4); 374(8); 368(3); 358(11); 342(3); 339(5); 329(9); 326(11); 317(7); 312(9); 303(2); 294(5); 284(20); 283(7); 268(22); 255(7); 241(4); 195(9); 177(10) M = 402 Da: 15-thioformyl-6-hydroxy-TGE (1) | 1/Major | O gain (+16) + 2H loss (−2) |
M = 404 Da: 6-hydroxy-TGE (2) | 2/Minor | O gain (+16) |
419: 401(1); 391(57); 385(29); 375(57); 371(14); 357(14); 351 (43); 347(1); 329(43); 327(29); 315(29); 301(29); 299(29); 295 (29); 285(28); 283(42); 271(14); 269(86); 257(14); 255(28); 227(14); 195(43); 177(14); 165(57); 151(14) M = 420 Da: 15-thioformyl-2,3-dihydro-2,6-dihydroxy-TGE (3) | 3/Medium | O gain (+16) + H2O gain (+18) + 2H loss (−2) |
M = 422 Da: 2,3-dihydro-2,6-dihydroxy-TGE (4) | 4/Minor | O gain (+16) + H2O gain (+18) |
423: 405(6); 395(25); 359(1); 339(19); 331(6); 307(1); 283 (6); 269(6); 257(100); 255(1); 229(13); 212(6); 185(13); 176(12); 120(13) M = 424 Da: 2,3,6,7-tetrahydro-2,6-dihydroxy-TGE (5) | 5/Minor | 2H2O gain (+36) |
433: 415(9); 405(13); 399(4); 387(9); 369(9); 315(9); 287(9); 269(100); 243(4); 213(9); 193(17); 177(4); 139(4) M = 434 Da: 15-thioformyl-2,6,3′-trihydroxy-TGE (6) or | 6/Medium | 3O gain (+48) + 2H loss (−2) |
435: 417(7); 389(7); 372(1); 363(2); 345(5); 301(10); 286(6); 280(1); 271(17); 269(100); 256 (3), 255(4); 241(2); 227(3); 212(7); 194(7); 176(1); 150(48) M = 436 Da: 15-thioformyl-2,3-dihydro-2,6,3′-trihydroxy-TGE (7) or or or | 7/Medium | 2H loss (−2) + 2O gain (+32) + H2O gain (+18) or 3O gain (+48) |
Product Mass, Characteristic Ions, m/z, (rel. int., % for EPI) | No. Oxidation Product/Intensity | Proposed Metabolic Reaction–Suggested Reactions |
---|---|---|
TGE [M-H]− = 387 Da m/z: EPI− | ||
435: 349(1); 286(1); 269(100); 241(1); 224(1); 213(1); 201(1); 181(1); 165(1); 157 (1); 121(2) M = 436 Da: 2,6,3′-trihydroxy-TGE (8) | 8/Major | 3O gain (+48) |
M = 438 Da: 2,3-dihydro-2,6,3′-trihydroxy-TGE (9) | 9/Minor | 2O gain (+32) + H2O gain (+18) |
451: 423(2); 285(100); 283(2); 269(3); 257(5); 229(2); 217(3); 213(1); 121(2) M = 452 Da: 2,6,8,3′-tetrahydroxy-TGE (10) | 10/Minor | 4O gain (+64) |
453: 438(67); 435(17); 425(50); 409(17); 407(33); 395(17); 364(100); 338(17); 309(33); 295(17); 287(67); 285(100); 269(17); 241(17); 229(17); 123(33) M = 454 Da: 2,3-dihydro-2,6,8,3′-tetrahydroxy-TGE (11) | 11/Medium | 3O gain (+48) + H2O gain (+18) |
467: 450(2); 449 (1); 434(61); 433(1); 421(2); 405(1); 370(4); 369(1); 328(13); 317(2); 301(10); 284(20); 283(17); 268(100); 267(7); 255(6); 239(4); 211(2); 193(6); 151(3); 121(3) M = 468 Da: 2, 6, 8,3′,5′-pentahydroxy-TGE (12) | 12/Minor | 5O gain (+80) |
469: 454(5); 441(7); 437(30); 425(6); 423(20); 411(5); 409(100); 397(4); 383(8); 380(4); 355(2); 353(20); 339(5); 325(13); 317(3); 311(7); 307(11); 303(7); 295(2); 285(28); 283(4); 269(8); 257(3); 241(4); 225(1); 199(2); 185(2); 171(6); 151(4); 147(2); 121(2) M = 470 Da: 2,3-dihydro-2,6,8,3′,5′-pentahydroxy-TGE (13) | 13/Medium | 4O gain (+64) + H2O gain (+18) |
485: 467(1); 451(3); 439(2); 437(30); 435(11); 409(100); 407(3); 393(6); 375(3); 350(3); 319(2); 301(5); 285(5); 269(5); 257(2); 243(1); 227(2); 199(2); 183(1); 151(2); 143(1); 121(2) M = 486 Da: 2,3-dihydro-2,6,8,3′,5′,6′-hexahydroxy-TGE (14) | 14/Medium | 5O gain (+80) + H2O gain (+18) |
501: 483(1); 473(1); 453(11); 437(7); 425(10); 409(100); 407(5); 393(5); 379(5); 364(8); 352(3); 336(3); 309(3); 291(2); 282(5); 268(2); 155(1); 139(1); 123(1) M = 502 Da: 2,3-dihydro-2,6,8,2′,3′,5′,6′-heptahydroxy-TGE (15) | 15/Minor | 6O gain (+96) + H2O gain (+18) |
520: 502(3); 476(6); 474(98); 457(58); 448(10); 435(83); 430(29); 429(6); 406(5); 404(8); 390(5); 372(3); 358(6); 353(6); 338(5); 326(6); 306(3); 283(4); 269(100); 197(5); 177(8); 121(10) M = 520 Da: 2-hydro-2,3,4,6,8,2′,3′,5′,6′-nonahydroxy-TGE (16) | 16/Minor | 6O gain (+96) + 2H2O gain (+36) |
536: 518(1); 502(1); 490(3); 473(11); 455(1); 454(1); 435(86); 429(1); 402(1); 384(1); 382(1); 370(3); 353(3); 338(1); 308(1); 285(2); 269(100); 214(2); 165(1); 121(2) M = 536 Da: 16-sulfenic-2-hydro-2,3,4,6,8,2′,3′,5′,6′-nonahydroxy-TGE (17) | 17/Minor | 7O gain (+112) + 2H2O gain (+36) |
Product Mass, Characteristic Ions m/z, (rel. int., % for EPI) | No. Oxidation Product/Intensity | Proposed Metabolic Reaction-Suggested Reactions |
---|---|---|
TGE [M-H]− = 387 Da m/z: EPI− | ||
423: 395(7); 339(7); 307(27); 287(3), 269(3); 257(100); 229(10); 213(1); 185(10); 177(3); 159(1); 143(1); 135(1); 121(10) M = 424 Da: 6,7,8,9-tetrahydro-6,8-dihydroxy-TGE (18) | 18/Medium | 2H2O gain (+36) |
435: 349(1); 286(1); 269(100); 241(1); 224(1); 213(1); 201(1); 181(1); 165(1); 157 (1); 121(2) M = 436 Da: 2,6,3′-trihydroxy-TGE (8) | 8/Major | 3O gain (+48) |
M = 438 Da: 2,3-dihydro-2,6,3′-trihydroxy-TGE (9) | 9/Minor | 2O gain (+32) + H2O gain (+18) |
451: 423(2); 285(100); 283(2); 269(3); 257(5); 229(2); 217(3); 213(1); 121(2) M = 452 Da: 2,6,8,3′-tetrahydroxy-TGE (10) | 10/Medium | 4O gain (+64) |
453: 438(67); 435(17); 425(50); 409(17); 407(33); 395(17); 364(100); 338(17); 309(33); 295(17); 287(67); 285(100); 269(17); 241(17); 229(17); 123(33) M = 454 Da: 2,3-dihydro-2,6,8,3′-tetrahydroxy-TGE (11) | 11/Medium | 3O gain (+48) + H2O gain (+18) |
467: 450(2); 434(61); 421(2); 370(4); 328(13); 317(2); 301(10); 284(20); 268(100); 255(6); 239(4); 211(2); 193(6); 151(3); 121(3) M = 468 Da: 2,6,8,3′,5′-pentahydroxy-TGE (12) | 12/Medium | 5O gain (+80) |
469: 454(5); 441(7); 437(30); 425(6); 423(20); 411(5); 409(100); 397(4); 383(8); 380(4); 355(2); 353(20); 339(5); 325(13); 317(3); 311(7); 307(11); 303(7); 295(2); 285(28); 283(4); 269(8); 257(3); 241(4); 225(1); 199(2); 185(2); 171(6); 151(4); 147(2); 121(2) M = 470 Da: 2,3-dihydro-2,6,8,3′,5′-pentahydroxy-TGE (13) | 13/Minor | 4O gain (+64) + H2O gain (+18) |
473: 457(1); 409(1); 399(13); 351(13); 323(1); 313(25); 307(100); 306(12); 305(1); 295(25); 284(1); 281(13); 269(63); 239(1); 223(13); 181(1); 177(88); 165(1); 139(1); 121(50) M = 474 Da: 2,3,6,7,8,9-hexahydro-2,6,8,3′,5′-pentahydroxy-TGE (19) | 19/Medium | 2O gain (+32) + 3 H2O gain (+54) |
485: 467(1); 451(3); 439(2); 437(30); 435(11); 409(100); 407(3); 393(6); 375(3); 350(3); 319(2); 301(5); 285(5); 269(5); 257(2); 243(1); 227(2); 199(2); 183(1); 151(2); 143(1); 121(2) M = 486 Da: 2,3-dihydro-2,6,8,3′,5′,6′-hexahydroxy-TGE (14) | 14/Minor | 5O gain (+80)+ H2O gain (+18) |
501: 483(2); 473(1); 453(3); 437(9); 425(8); 409(100); 407(9); 393(5); 379(5); 364(11); 352(3); 336(1); 309(3); 291(7); 282(5); 268(1); 155(1); 139(1); 123(1) M = 502 Da: 2-hydro-2,6,8,2′,3′,5′,6′-heptahydroxy-TGE (15) | 15/Minor | 6O gain (+96) + H2O gain (+18) |
520: 502(6); 476(2); 474(30); 457(16); 448(7); 435(13); 430(12); 429(7); 404(5); 390(1); 358(3); 353(7); 338(4); 326(9); 306(4); 283(3); 269(100); 197(6); 177(5); 121(12) M = 520 Da: 2,3-dihydro-2,3,4,6,8,2′,3′,5′,6′-nonahydroxy-TGE (16) | 16/Minor | 6O gain (+96) + 2H2O gain (+36) |
536: 518(2); 502(2); 490(2); 473(4); 455(1); 435(12); 429(1); 402(1); 370(3); 353(4); 338(1); 308(1); 285(2); 269(100); 214(1); 165(1); 121(3) M = 536 Da: 16-sulfenic-2-hydro-2,3,4,6,8,2′,3′,5′,6′-nonahydroxy-TGE (17) | 17/Minor | 7O gain (+112) + 2H2O gain (+36) |
Compound | BDE |
---|---|
Phenol | 82.90 |
Genistein | 81.56 |
Thiogenistein | 81.82 |
Trolox | 73.91 |
Curcumin (*) | 75.56 |
Antioxidant | ΔG, kcal/mol |
---|---|
Genistein (GE) | 16.02 |
Genistein thiolated at O-7 (TGE) | 15.37 |
Genistein thiolated at O-4′ | 14.88 |
Genistein thiolated at O-5 | 14.99 |
Genistein thiolated at O-7 by a modified thiol residue with the extra -CH2- group (M26P) | 14.49 |
Trolox | 11.44 |
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Stolarczyk, E.U.; Strzempek, W.; Łaszcz, M.; Leś, A.; Menaszek, E.; Stolarczyk, K. Thiogenistein—Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products. Int. J. Mol. Sci. 2022, 23, 7816. https://doi.org/10.3390/ijms23147816
Stolarczyk EU, Strzempek W, Łaszcz M, Leś A, Menaszek E, Stolarczyk K. Thiogenistein—Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products. International Journal of Molecular Sciences. 2022; 23(14):7816. https://doi.org/10.3390/ijms23147816
Chicago/Turabian StyleStolarczyk, Elżbieta U., Weronika Strzempek, Marta Łaszcz, Andrzej Leś, Elżbieta Menaszek, and Krzysztof Stolarczyk. 2022. "Thiogenistein—Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products" International Journal of Molecular Sciences 23, no. 14: 7816. https://doi.org/10.3390/ijms23147816