Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates
Abstract
1. Introduction
2. Results and Discussion
2.1. Results
2.1.1. Chenical Synthesis
2.1.2. Biological Screening
In Vitro Cytotoxic Activities
In Vivo Anti-Ovarian Cancer
2.1.3. Inhibition of Topoisomerase II Activities
2.1.4. In Vitro Kinase Assay
2.2. Discussion
3. Materials and Methods
3.1. Chemical Synthesis
3.1.1. Synthesis of 3-Hydroxy-16-[substituted]-estra-1(10),2,4-trien-17-ones (2a,b)
3-Hydroxy-16-[ethylene]-estra-1(10),2,4-trien-17-one (2b)
3.1.2. Synthesis of 16-(α-alkoxy-alkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol and their N-substituted derivatives (3a–l)
16-(α-Methoxy-methane)-17-hydrazino-estra-1(10),2,4-trien-[17,16-c]-3-ol (3a)
16-(α-Methoxy-ethane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3b)
16-(α-Ethoxy-methane)-17-hydrazino-estra-1(10),2,4-trien-[17,16-c]-3-ol (3c)
16-(α-Ethoxy-ethane)-17-hydrazino-estra-1(10),2,4-trien-[17,16-c]-3-ol (3d)
16-(α-Methoxy-methane)-17-[N-methyl-hydrazino]estra-1(10),2,4-trien[17,16-c]-3-ol (3e)
16-(α-Methoxy-ethane)-17-[N-methyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3f)
16-(α-Ethoxy-methane)-17-[N-methyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3g)
16-(α-Ethoxy-ethane)-17-[N-methyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3h)
16-(α-Methoxy-methane)-17-[N-phenyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3i)
16-(α-Methoxy-ethane)-17-[N-phenyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3j)
16-(α-Ethoxy-methane)-17-[N-phenyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3k)
16-(α-Ethoxy-ethane)-17-[N-phenyl-hydrazino]-estra-1(10),2,4-trien-[17,16-c]-3-ol (3l)
3.1.3. Synthesis of pyrazoline-3-ol derivatives (4a–d)
1`-Methyl-1`H-estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol (4a)
1`-Methyl -1`H-5`-methyl-estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol (4b)
1`-Phenyl-1`H-estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol (4c)
1`-Phenyl-1`H-5`-methyl-estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol (4d)
3.2. Biological Screening
3.2.1. In Vitro Cytotoxic Activities
3.2.2. In Vitro Anti-Ovarian Xenograft Model
3.2.3. Topoisomerase II Inhibition
3.2.4. In Vitro Kinase Inhibition
Protein Expression and Purification
In Vitro ELISA-Based Kinase Assay
3.2.5. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
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El-Naggar, M.; E. Amr, A.E.-G.; Fayed, A.A.; A. Elsayed, E.; A. Al-Omar, M.; Abdalla, M.M. Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates. Molecules 2019, 24, 2054. https://doi.org/10.3390/molecules24112054
El-Naggar M, E. Amr AE-G, Fayed AA, A. Elsayed E, A. Al-Omar M, Abdalla MM. Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates. Molecules. 2019; 24(11):2054. https://doi.org/10.3390/molecules24112054
Chicago/Turabian StyleEl-Naggar, Mohamed, Abd El-Galil E. Amr, Ahmed A. Fayed, Elsayed A. Elsayed, Mohamed A. Al-Omar, and Mohamed M. Abdalla. 2019. "Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates" Molecules 24, no. 11: 2054. https://doi.org/10.3390/molecules24112054
APA StyleEl-Naggar, M., E. Amr, A. E.-G., Fayed, A. A., A. Elsayed, E., A. Al-Omar, M., & Abdalla, M. M. (2019). Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates. Molecules, 24(11), 2054. https://doi.org/10.3390/molecules24112054