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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Synthesis and Anti-cancer Activity of Paclitaxel−Coumarin Conjugate

Author(s): Zurong Song*, Qin Lu, Ali Tao and Tianchen Wu

Volume 18, Issue 6, 2021

Published on: 03 March, 2021

Page: [587 - 591] Pages: 5

DOI: 10.2174/1570179418666210303113406

Price: $65

Abstract

Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence.

Objective: Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand.

Materials and Methods: To synthsize paclitaxel-coumarin conjugate via click chemistry and to investigate anticancer activity by MTT assay and the scratch test.

Results and Discussion: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel.

Conclusion: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development of paclitaxel through fluorescence.

Keywords: Paclitaxel, coumarin, conjugate, synthesis, anti-tumor activity, anti-metastasis.

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[1]
Abu Samaan, T.M.; Samec, M.; Liskova, A.; Kubatka, P.; Büsselberg, D. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules, 2019, 9, 789.
[http://dx.doi.org/10.3390/biom9120789]
[2]
Nikolic, V.D.; Savic, I.M.; Savic, I.; Nikolic, L.B.; Stankovic, M.Z.; Marinkovic, V.D. Paclitaxel as an anticancer agent: Isolation, activity, synthesis and stability. Open Med., 2011, 6, 527.
[http://dx.doi.org/10.2478/s11536-011-0074-5]
[3]
Zhang, L.; Zheng, C.Y.; Cao, J.H.; Luo, S.L. Efficacy of paclitaxel, carboplatin, and bevacizumab for cervical cancer: A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(24)e20558
[http://dx.doi.org/10.1097/MD.0000000000020558] [PMID: 32541479]
[4]
Shi, C.; Chen, Q.; Shen, S.; Wu, R.; Yang, B.; Liu, Q.; Xu, Q. Paclitaxel combined with oxaliplatin as first-line chemotherapy for locally advanced or metastatic gastric cancer. Expert Rev. Anticancer Ther., 2015, 15(5), 595-601.
[http://dx.doi.org/10.1586/14737140.2015.1026807] [PMID: 25827975]
[5]
Rosen, V.M.; Guerra, I.; McCormack, M.; Nogueira-Rodrigues, A.; Sasse, A.; Munk, V.C.; Shang, A. Rosen.;V.M.;Ines.;McCormack.;Mary.; NogueiraRodrigues.; Angélica.; Sasse.; Andre. Systematic review and network meta-analysis of bevacizumab plus first-line topotecan-paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent, recurrent, or metastatic cervical cancer. Int. J. Gynecol. Cancer, 2017, 27(6), 1237-1246.
[http://dx.doi.org/10.1097/IGC.0000000000001000] [PMID: 28448304]
[6]
Li, Y.; Sui, X.; Su, Z.; Yu, C.; Shi, X.; Johnson, N.L.; Chu, F.; Li, Y.; Li, K.; Ding, X. Meta-analysis of paclitaxel-based chemotherapy combined with traditional chinese medicines for gastric cancer treatment. Front. Pharmacol., 2020, 11, 132.
[http://dx.doi.org/10.3389/fphar.2020.00132] [PMID: 32174834]
[7]
Kong, F.W.; Wang, W.M.; Liu, L.; Wu, W.B.; Wang, X.; Zhang, M. First-line albumin-bound paclitaxel/carboplatin plus apatinib in advanced pulmonary sarcomatoid carcinoma: A case series and review of the literature. Medicine (Baltimore), 2020, 99(23)e20667
[http://dx.doi.org/10.1097/MD.0000000000020667] [PMID: 32502055]
[8]
Wen, G.; Qu, X.X.; Wang, D.; Chen, X.X.; Tian, X.C.; Gao, F.; Zhou, X.L. Recent advances in design, synthesis and bioactivity of paclitaxel-mimics. Fitoterapia, 2016, 110, 26-37.
[http://dx.doi.org/10.1016/j.fitote.2016.02.010] [PMID: 26906104]
[9]
Meng, Z.; Lv, Q.; Lu, J.; Yao, H.; Lv, X.; Jiang, F.; Lu, A.; Zhang, G. Prodrug strategies for paclitaxel. Int. J. Mol. Sci., 2016, 17(5), 796.
[http://dx.doi.org/10.3390/ijms17050796] [PMID: 27223283]
[10]
Qin, H.L.; Zhang, Z.W.; Ravindar, L.; Rakesh, K.P. Antibacterial activities with the structure-activity relationship of coumarin derivatives. Eur. J. Med. Chem., 2020, 207112832
[http://dx.doi.org/10.1016/j.ejmech.2020.112832] [PMID: 32971428]
[11]
Hussain, M.I.; Syed, Q.A.; Khattak, M.N.K.; Hafez, B.; Reigosa, M.J.; El-Keblawy, A. Natural product coumarins: Biological and pharmacological perspectives. Biologia, 2019, 74, 863.
[http://dx.doi.org/10.2478/s11756-019-00242-x]
[12]
Garg, S.S.; Gupta, J.; Sharma, S.; Sahu, D. An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur. J. Pharm. Sci., 2020, 152105424
[http://dx.doi.org/10.1016/j.ejps.2020.105424] [PMID: 32534193]
[13]
Zhang, L.; Xu, Z. Coumarin-containing hybrids and their anticancer activities. Eur. J. Med. Chem., 2019, 181111587
[http://dx.doi.org/10.1016/j.ejmech.2019.111587] [PMID: 31404864]
[14]
Al-Warhi, T.; Sabt, A.; Elkaeed, E.B.; Eldehna, W.M. Recent advancements of coumarin-based anticancer agents: An up-to-date review. Bioorg. Chem., 2020, 103104163
[http://dx.doi.org/10.1016/j.bioorg.2020.104163] [PMID: 32890989]
[15]
Sun, X-y.; Liu, T.; Sun, J. Wang,X.J. Synthesis and application of coumarin fluorescence probes. RSC Adv, 2020, 10, 10826-10847.
[http://dx.doi.org/10.1039/C9RA10290F]
[16]
Mu, J.; Zhong, H.; Zou, H.; Liu, T.; Yu, N.; Zhang, X.; Xu, Z.; Chen, Z.; Guo, S. Acid-sensitive PEGylated paclitaxel prodrug nanoparticles for cancer therapy: Effect of PEG length on antitumor efficacy. J. Control. Release, 2020, 326, 265-275.
[http://dx.doi.org/10.1016/j.jconrel.2020.07.022] [PMID: 32687940]
[17]
Yu, N.; Li, J.; Zhang, Y.; Ding, D.; Xu, H. Superior antitumor effect of self-assembly supramolecular paclitaxel nanoparticles. RSC Adv, 2020, 10, 12999-13005.
[http://dx.doi.org/10.1039/D0RA01117G]
[18]
Xuan, Y. Dai.; Guang, X. Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance. Eur. J. Med. Chem., 2019, 171, 104-115.

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