Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Anticancer Evaluation
2.3. Molecular Modeling
3. Materials and Methods
3.1. Chemistry
3.1.1. General Procedure for the Synthesis of Monoquaternary Salts 3a–d, 7a–d and 10a–d
3.1.2. General Procedure for the Preparation of Compounds 5a–d, 8a–d and 11a–d
3.1.3. 7-(2-Oxo-2-(3,4,5-trimethoxyphenyl)ethyl)-1,7-phenanthrolin-7-ium Bromide 3a
3.1.4. 7-(2-(3,5-Dimethoxyphenyl)-2-oxoethyl)-1,7-phenanthrolin-7-ium Bromide 3b
3.1.5. 7-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)-1,7-phenanthrolin-7-ium Bromide 3c
3.1.6. 7-(2-(4-Bromophenyl)-2-oxoethyl)-1,7-phenanthrolin-7-iumbromide 3d
3.1.7. 4-(2-(3,4,5-Trimethoxyphenyl)-2-oxoethyl)-4,7-phenanthrolin-4-ium bromide 7a
3.1.8. 4-(2-(3,5-Dimethoxyphenyl)-2-oxoethyl)-4,7-phenanthrolin-4-ium Bromide 7b
3.1.9. 4-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)-4,7-phenanthrolin-4-ium Bromide 7c
3.1.10. 4-(2-(4-Bromophenyl)-2-oxoethyl)-4,7-phenanthrolin-4-ium Bromide 7d
3.1.11. 1-(2-Oxo-2-(3,4,5-trimethoxyphenyl)ethyl)-1,10-phenanthrolin-1-ium Bromide 10a
3.1.12. 1-(2-(3,5-Dimethoxyphenyl)-2-oxoethyl)-1,10-phenanthrolin-1-ium Bromide 10b
3.1.13. 1-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)-1,10-phenanthrolin-1-ium Bromide 10c
3.1.14. 1-(2-(4-Bromophenyl)-2-oxoethyl)-1,10-phenanthrolin-1-ium Bromide 10d
3.1.15. Ethyl 9-(3,4,5-trimethoxybenzoyl)pyrrolo[1,2-i][1,7]phenanthroline-7-carboxylate 5a
3.1.16. Ethyl 9-(3,5-dimethoxybenzoyl)pyrrolo[1,2-i][1,7]phenanthroline-7-carboxylate 5b
3.1.17. Ethyl 9-(3,4-dimethoxybenzoyl)pyrrolo[1,2-i][1,7]phenanthroline-7-carboxylate 5c
3.1.18. Ethyl 9-(4-bromobenzoyl)pyrrolo[1,2-i][1,7]phenanthroline-7-carboxylate 5d
3.1.19. Ethyl 9-(3,4,5-trimethoxybenzoyl)pyrrolo[2,1-c][4,7]phenanthroline-7-carboxylate 8a
3.1.20. Ethyl 9-(3,5-dimethoxybenzoyl)pyrrolo[2,1-c][4,7]phenanthroline-7-carboxylate 8b
3.1.21. Ethyl 9-(3,4-dimethoxybenzoyl)pyrrolo[2,1-c][4,7]phenanthroline-7-carboxylate 8c
3.1.22. Ethyl 9-(4-bromobenzoyl)pyrrolo[2,1-c][4,7]phenanthroline-7-carboxylate 8d
3.1.23. Ethyl 11-(3,4,5-trimethoxybenzoyl)pyrrolo[1,2-a][1,10]phenanthroline-9-carboxylate 11a
3.1.24. Ethyl 11-(3,5-dimethoxybenzoyl)pyrrolo[1,2-a][1,10]phenanthroline-9-carboxylate 11b
3.1.25. Ethyl 11-(3,4-dimethoxybenzoyl)pyrrolo[1,2-a][1,10]phenanthroline-9-carboxylate 11c
3.1.26. Ethyl 11-(4-bromobenzoyl)pyrrolo[1,2-a][1,10]phenanthroline-9-carboxylate 11d
3.2. Cell Proliferation Assay
3.3. Molecular Modelling
4. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Cell Type | Compound | 5c | 8a | 8b | 11c | Phenstatin |
---|---|---|---|---|---|---|
Cell Line | GI (%) (10−5 M) a | |||||
Leukemia | CCRF-CEM | 0 | 37 | 1 | 80 | 94 |
K-562 | 8 | 87 | 14 | 85 | 91 | |
SR | 12 | 86 | 24 | 77 | 93 | |
HL-60(TB) | 13 | 87 | 25 | 96 | 100 b,f | |
MOLT-4 | 22 | 69 | 23 | 66 | 85 | |
RPMI-8226 | 0 | 37 | 0 | 95 | 87 | |
Non-small Cell Lung Cancer | A549/ATCC | 3 | 36 | 2 | 63 | 82 |
HOP-92 | 0 | 45 | 16 | 80 | 48 | |
HOP-62 | 8 | 38 | 7 | 70 | 77 | |
NCI-H460 | 0 | 18 | 2 | 89 | 93 | |
NCI-H522 | 9 | 77 | 19 | 99 | 88 | |
Colon Cancer | COLO205 | 0 | 67 | 0 | 100b,c | 58 |
HCT-116 | 0 | 78 | 24 | 73 | 96 | |
HCT-15 | 8 | 56 | 18 | 69 | 96 | |
HT-29 | 0 | 80 | 20 | 93 | 85 | |
SW-620 | 8 | 76 | 5 | 87 | 78 | |
KM12 | 3 | 58 | 11 | 71 | 91 | |
CNS Cancer | SF-295 | 0 | 37 | 0 | 88 | 100 b,g |
SF-539 | 0 | 44 | 4 | 91 | 100 b,h | |
SNB-75 | 21 | 35 | 18 | 82 | 100 b,i | |
U251 | 0 | 49 | 1 | 75 | 79 | |
Melanoma | LOX IMVI | 4 | 53 | 0 | 68 | 85 |
M14 | 0 | 68 | 19 | 92 | 100 b,j | |
MDA-MB-435 | 0 | 91 | 7 | 100b,d | 100 b,k | |
UACC-62 | 0 | 42 | 0 | 53 | 55 | |
SK-MEL-2 | 0 | 59 | 0 | 81 | 40 | |
SK-MEL-5 | 1 | 66 | 1 | 83 | 100 b,l | |
Ovarian Cancer | OVCAR-3 | 0 | 39 | 0 | 90 | 100 b,m |
NCI/ADR-RES | 6 | 66 | 4 | 78 | 100 b,n | |
SK-OV-3 | 16 | 22 | 28 | 87 | 53 | |
OVCAR-8 | 9 | 44 | 0 | 71 | 86 | |
Renal cancer | A498 | 0 | 39 | 0 | 100b,e | 25 |
RXF393 | 0 | 33 | 0 | 75 | 99 | |
786-0 | 0 | 22 | 0 | 67 | - | |
Breast cancer | MCF7 | 19 | 71 | 13 | 78 | 94 |
MDA-MB-468 | 0 | 30 | 0 | 61 | 100 b,o | |
HS 578T | 3 | 27 | 4 | 75 | 71 | |
BT-549 | 0 | 31 | 18 | 67 | 88 | |
Prostate cancer | PC-3 | 13 | 36 | 18 | 78 | 80 |
DU-145 | 0 | 11 | 0 | 78 | 90 |
Cell Type | Compound→ | 11c | Phenstatin |
---|---|---|---|
Cell Line↓ | GI50 (μM) b | ||
Leukemia | HL-60(TB) | 2.78 | 0.011 |
SR | 0.807 | <0.010 | |
CCRF-CEM | 3.13 | 0.034 | |
Non-small Cell Lung Cancer | NCI-H460 | 1.58 | 0.033 |
NCI-H522 | 0.611 | 0.027 | |
HOP-62 | 3.78 | 0.073 | |
Colon Cancer | HCT-116 | 0.619 | 0.038 |
HCT-15 | 1.25 | <0.010 | |
HT29 | 1.42 | 2.95 | |
SW-620 | 0.930 | <0.010 | |
KM12 | 1.30 | <0.010 | |
CNS Cancer | SF-295 | 0.800 | 0.367 |
SF-539 | 2.10 | 0.011 | |
SNB-75 | 2.04 | <0.010 | |
U251 | 3.61 | 0.043 | |
Melanoma | SK-MEL-5 | 0.836 | 0.040 |
M14 | 0.648 | <0.010 | |
MDA-MB-435 | 0.296 | <0.010 | |
UACC-62 | 0.918 | 0.448 | |
LOXIMVI | 2.60 | 0.013 | |
MALME-3M | 1.24 | - | |
SK-MEL-2 | 2.67 | 0.520 | |
SK-MEL-28 | 3.70 | 65.20 | |
Ovarian Cancer | OVCAR-3 | 1.08 | 0.021 |
NCI/ADR-RES | 0.948 | 0.012 | |
IGROV1 | 2.33 | 0.18 | |
OVCAR-8 | 3.73 | 0.042 | |
Renal Cancer | 786-0 | 2.34 | 0.905 |
A498 | 2.82 | 2.28 | |
UO-31 | 0.891 | 0.074 | |
ACHN | 2.40 | 0.042 | |
RXF 393 | 2.06 | 0.016 | |
Breast cancer | MCF7 | 2.25 | 0.033 |
HS 578T | 3.04 | 0.031 | |
MDA-MB-231/ATCC | 2.66 | 0.029 | |
BT-549 | 1.94 | 0.034 | |
T-47D | 2.37 | 30.4 | |
MDA-MB-468 | 2.83 | 2.71 | |
Prostate cancer | PC-3 | 0.960 | 0.045 |
DU-145 | 3.44 | 0.039 |
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Al Matarneh, C.M.; Amarandi, R.M.; Craciun, A.M.; Mangalagiu, I.I.; Zbancioc, G.; Danac, R. Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines. Molecules 2020, 25, 527. https://doi.org/10.3390/molecules25030527
Al Matarneh CM, Amarandi RM, Craciun AM, Mangalagiu II, Zbancioc G, Danac R. Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines. Molecules. 2020; 25(3):527. https://doi.org/10.3390/molecules25030527
Chicago/Turabian StyleAl Matarneh, Cristina Maria, Roxana Maria Amarandi, Anda Mihaela Craciun, Ionel I. Mangalagiu, Gheorghita Zbancioc, and Ramona Danac. 2020. "Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines" Molecules 25, no. 3: 527. https://doi.org/10.3390/molecules25030527