Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones
Abstract
:1. Introduction
2. Results
2.1. MTT Breast Cancer
2.2. Docking Results
3. Discussion
4. Materials and Methods
4.1. Compounds
4.2. Cytotoxicity Assay
4.3. Cell Viability Assay
4.4. Ligands
4.5. Sequence Alignment
4.6. Docking
4.7. Vina
4.8. Glide
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Uniprot, Isoform | ζ | Ι | δ | θ | ε | α | β |
---|---|---|---|---|---|---|---|
sp|P41743|KPCI_HUMAN, ζ | 100 | 72.81 | 36.82 | 36.86 | 44.78 | 43.57 | 43.48 |
sp|P41743|KPCI_HUMAN, ι | 72.81 | 100 | 36.14 | 36.52 | 43.91 | 45.36 | 44.21 |
sp|Q05655|KPCD_HUMAN, δ | 36.82 | 36.14 | 100 | 64.89 | 43.88 | 47.61 | 48.99 |
sp|Q04759|KPCT_HUMAN, θ | 36.86 | 36.52 | 64.89 | 100 | 43.31 | 48.51 | 47.64 |
sp|Q02156|KPCE_HUMAN, ε | 44.78 | 43.91 | 43.88 | 43.31 | 100 | 52.9 | 53.14 |
sp|P17252|KPCA_HUMAN, α | 43.57 | 45.36 | 47.61 | 48.51 | 52.9 | 100 | 79.01 |
sp|P05771|KPCB_HUMAN, β | 43.48 | 44.21 | 48.99 | 47.64 | 53.14 | 79.01 | 100 |
Compound | 5f9e (Isoform θ) | 2i0e (Isoform βII) | 3zh8 (Isoform ι) | 4ra4 (Isoform α) | 1ptr (Isoform δ) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Vina | Glide XP | MMGBSA | Vina | Glide XP | MMGBSA | Vina | Glide XP | MMGBSA | Vina | Glide XP | MMGBSA | Vina | Glide XP | MMGBSA | |
PMA | −7.4 | −8.0 | −4.84 | −40.13 | −7.2 | −6.4 | −4.7 | −4.41 | −42.12 | ||||||
ARA | −6.3 | −7.8 | −1.00 | −40.95 | −6.5 | −5.6 | −4.4 | −1.85 | −18.56 | ||||||
5VS1001 (5f9e co-cryst.) | −10.5 | −7.2 | −40.48 | ||||||||||||
PDS 902 (2i0e co-cryst.) | –11.0 | −10.02 | −56.23 | ||||||||||||
C581582 (3zh8 co-cryst.) | −9.9 | −8.0 | −58.56 | ||||||||||||
3KZ701 (4ra4 co-cryst.) | −10.4 | −10.0 | 0 | ||||||||||||
PRB3 (1ptr co-cryst.) | −6.3 | −4.25 | −27.00 | ||||||||||||
1 (DeRoy) | –9.3 | −5.8 | −44.29 | −12.0 | −6.21 | −30.81 | −8.4 | −5.6 | −36.23 | −8.4 | −6.7 | 0 | −6.2 | −4.13 | −29.39 |
2 (Roy) | –9 | −10.4 | −8.8 | −8 | −6.7 | ||||||||||
3 (ParvD) | –9.8 | −2.0 | −12.0 | −5.84 | −9.8 | −6.91 | −9.3 | −4.84 | −8.4 | −4.68 | |||||
4 (RoyBz) | –9.3 | −9.4 | −9.0 | −8.7 | −6.9 | ||||||||||
5 (RoyBzCl) | –8.8 | −9.8 | −9.4 | −8.4 | −6.7 | ||||||||||
6 (RoyPr2) | –8.7 | −7.9 | −7.4 | −7.5 | −6.3 | ||||||||||
7 (DihidroxyRoy) | –8.3 | −10.5 | −8.7 | −7.6 | −7.9 |
Compounds | PKC Isoform | |||
---|---|---|---|---|
α | βI | ι | θ | |
DeRoy (1) | Met 417 (L), Ala 480 (L), Met 470 (L), Lys 368 (H), Val 353 (L), Leu 345 (L) | Met 473 (L), Ala 483 (L), Phe 485 (L), Leu 394 (L), Phe 353 (L), Val 356 (L), Lys 371 (L), Phe 418 (L), Met 420 (L), Ala 369 (L), Leu 348 (L) | Leu 376 (L), Thr 386 (R), Val 307 (L), Phe 297 (L), Ile 323 (L), Lys 274 (L), Val 259 (L), Ile 251 (L) | Leu 511 (L), Ala 521 (L), Met 458 (L), Lys 409 (H), Val 394 (H), Phe 391 (R) |
Roy (2) | Val 420 (H), Lys 368 (L), Ala 366 (L), Met 417 (L), Val 353 (L), Leu 345 (H, L) | Met 473 (L), Ala 483 (L), Phe 353 (L), Met 420 (L), Lys 371 (L), Val 356 (L) | Asp 373 (H), Ile 323 (L) | Leu 511 (L), Asn 509 (L), Ala 521 (L), Met 458 (L), Lys 409 (L), Val 394 (L), Leu 386 (L) |
ParvD (3) | Met 470 (L), Val 353 (L), Ala 366 (L), Leu 345 (L), Met 417 (R, L), Lys 368 (L), Leu 391 (L), Ala 480 (L) | Met 473 (L), Tyr 422 (L), Leu 348 (L), Val 356 (L), Ala 483 (L), Ala 369 (L), Asn 471 (H), Phe 485 (L), Leu 394 (L), Lys 371 (L) | Ile 251 (L), Val 259 (L), Leu 376 (L), Tyr 325 (H), Val 259 (L), Thr 386 (L), Lys 274 (L), Ile 323 (L), Val 307 (L), Phe 297 (L) | Leu 511 (L), Ala 521 (L), Met 458 (L), Ala 407 (L), Val 394 (L), Phe 391 (L) |
RoyBz (4) | Asp 424 (H), Ala 366 (L), Val 353 (L), Met 417 (L), Lys 368 (L), Ala 480 (L) | Leu 348 (L), Met 473 (L), Val 356 (L), Phe 353 (L), Lys 371 (L), Met 420 (L), Ala 483 (L) | Phe 333 (L, R), Asp 330 (H), Ile 251 (L), Leu 376 (L), Val 259 (L), Thr 386 (R), Ala 272 (L), Ile 323 (L), Val 307 (L) | Gly 464 (L), Phe 391 (L), Val 394 (L), Ala 407 (L), Met 458 (L), Ala 521 (L), Asp 522 (L), Lys 409 (H) |
RoyBzCl (5) | Asp 424 (H), Gly 423 (L), Met 343 (R, L), Val 353 (L), Phe 350 (L), Lys 368 (L), Met 417 (L), Ala 480 (L) | Met 473 (L), Ala (483), Leu 394 (L), Met 420 (R, L), Lys 371 (L), Val 356 (L), Phe 353 (L), Leu 348 (L) | Phe 333 (R), Asp 330 (H), Thr 386 (R), Val 307 (L), Ile 323 (R), Ala 272 (R), Val 259 (R, L), Ile 251 (L), Arg 253 (R, L) | Leu 511 (L), Ala 521 (L), Lys 506 (L), Phe 391 (R), Val 394 (L), Leu 386 (R), Tyr 460 (L) |
RoyPr2 (6) | Asp 424 (H), Met 470 (L), Val 420 (L), Met 417 (L), Ala 366 (L), Val 353 (L) | Ala 483 (L), Phe 383 (L), Lys 371 (L), Val 356 (L), Leu 348 (L) | Thr 386 (H), Leu 376 (L), Ile 251 (L), Val 259 (L), Ala 257 (L) | Leu 511 (L), Ala 521 (L), Met 458 (L), Lys 409 (H, L), Ala 407 (L), Val 394 (L), Phe 391 (L) |
DihydroxyRoy (7) | Met 470 (L), Val 420 (H), Met 417 (L), Lys 368 (L), Leu 345 (H, L) | Phe 353 (L), Leu 348 (L), Val 356 (L), Lys 371 (L), Met 420 (R, L), Leu 394 (L), Phe 485 (L), Ala 483 (L) | Asp 373, Val 259, Lys 274, Ala 272, Ile 323 | Leu 511 (L), Ala 521 (L), Phe 523 (L), Leu 432 (L), Met 458 (L), Lys 409 (L), Val 394 (L), Leu 386 (L), Phe 391 (R) |
PKCα | PKC βI | PKCι | PKCθ |
---|---|---|---|
Met 470 | Met 473 | Leu 376 | Leu 511 |
Ala 480 | Ala 483 | Thr 386 | Ala 521 |
Thr 401 | Thr 404 | Val 307 | Thr 442 |
Met 417 | Met 420 | Ile 323 | Met 458 |
Lys 368 | Lys 371 | Lys 274 | Lys 409 |
Val 353 | Val 356 | Val 259 | Val 394 |
Leu 345 | Leu 348 | Ile 251 | Leu 386 |
Compound | Total Solvent Accessible Area (Å2) | Solved Exposed Area in Docked Pose (Å2) | Exposed Surface Ratio % | logP |
---|---|---|---|---|
DeRoy (1) | 268.47 | 142.36 | 53.02 | 4.53 |
Roy (2) | 318.47 | 209.29 | 65.71 | 2.65 |
ParvD (3) | 171.75 | 355.37 | 48.12 | 5.64 |
RoyBz (4) | 469.79 | 260.01 | 55.35 | 7.88 |
RoyBzCl (5) | 504.92 | 323.30 | 64.03 | 8.8 |
RoyPr2 (6) | 403.77 | 207.97 | 51.50 | 4.87 |
DihidroxyRoy (7) | 285.37 | 165.58 | 58.02 | 2.52 |
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Isca, V.M.S.; Sencanski, M.; Filipovic, N.; Dos Santos, D.J.V.A.; Čipak Gašparović, A.; Saraíva, L.; Afonso, C.A.M.; Rijo, P.; García-Sosa, A.T. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. Int. J. Mol. Sci. 2020, 21, 3671. https://doi.org/10.3390/ijms21103671
Isca VMS, Sencanski M, Filipovic N, Dos Santos DJVA, Čipak Gašparović A, Saraíva L, Afonso CAM, Rijo P, García-Sosa AT. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. International Journal of Molecular Sciences. 2020; 21(10):3671. https://doi.org/10.3390/ijms21103671
Chicago/Turabian StyleIsca, Vera M. S., Milan Sencanski, Nenad Filipovic, Daniel J. V. A. Dos Santos, Ana Čipak Gašparović, Lucília Saraíva, Carlos A. M. Afonso, Patrícia Rijo, and Alfonso T. García-Sosa. 2020. "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones" International Journal of Molecular Sciences 21, no. 10: 3671. https://doi.org/10.3390/ijms21103671