Citation: Hong Chen, Fang Xu, Bing-Bing Xu, Jing-Yi Xu, Bin-Hao Shao, Bi-Yun Huang, Mu Yuan. Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines[J]. Chinese Chemical Letters, ;2016, 27(02): 277-282. doi: 10.1016/j.cclet.2015.09.016 shu

Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

Hong Chen ^a,b ,
Fang Xu ^b ,
Bing-Bing Xu ^b ,
Jing-Yi Xu ^b ,
Bin-Hao Shao ^b ,
Bi-Yun Huang ^b ,
Mu Yuan ^b,,

a.
a. College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022, China;
b.
b. Pharmaceutical Research Center, Guangzhou Medical University, Guangzhou 510182, China

Corresponding author: Mu Yuan,
Received Date: 7 April 2015
Available Online: 9 June 2015
Fund Project: the China Postdoctoral Science Foundation (Nos. 2013M542165, 2013M531837) (No. cx2d1127) the National Science Foundation of Guangdong Province (No. S2013040014088) (Nos. 2013M542165, 2013M531837)the Guangzhou Postdoctoral Scientific Research Foundation (Nos. Q130, Q074). (No. S2013040014088)

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17 and 20 exhibited strong cytotoxic activities against the tested cancer cell lines (IC₅₀ <3 µmol/L). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.
- Synthesis,
- Arylpiperazine derivatives,
- Cytotoxic activity,
- CCK-8,
- Structure-activity relationship
1. [1]
  [1] R.T. Greenlee, M.B. Hill-Harmon, T. Murray, M. Thun, Cancer statistics 2001, CA, Cancer J. Clin. 51 (2001) 15-36.
2. [2]
  [2] M. Quinn, P. Babb, Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons, BJU Int. 90 (2002) 162-173.
3. [3]
  [3] H. Grönberg, Prostate cancer epidemiology, Lancet 361 (2003) 859-864.
4. [4]
  [4] J.T. Isaacs, Role of androgens in prostatic cancer, Vitam. Horm. 49 (1994) 433-502.
5. [5]
  [5] A. Beedassy, G. Cardi, Chemotherapy in advanced prostate cancer, Semin. Oncol. 26 (1999) 428-438.
6. [6]
  [6] C. Falciani, J. Brunetti, C. Pagliuca, et al., Design and in vitro evaluation of branched peptide conjugates: turning nonspecific cytotoxic drugs into tumor-selective agents, ChemMedChem 5 (2010) 567-574.
7. [7]
  [7] I. Tannock, Cell kinetics and chemotherapy: a critical review, Cancer Treat. Rep. 62 (1978) 1117-1133.
8. [8]
  [8] K. Vinaya, C.V. Kavitha, S. Chandrappa, et al., Synthesis and antileukemic activity of novel 4-(3-(piperidin-4-yl) propyl) piperidine derivatives, Chem. Biol. Drug Des. 78 (2011) 622-630.
9. [9]
  [9] F. Berardi, C. Abate, S. Ferorelli, et al., Novel 4-(4-aryl)cyclohexyl-1-(2-pyridyl) piperazines as Δ₈-Δ₇ sterol isomerase (emopamil binding protein) selective ligands with antiproliferative activity, J. Med. Chem. 51 (2008) 7523-7531.
10. [10]
  [10] C. Abate, M. Niso, M. Contino, et al., 1-Cyclohexyl-4-(4-arylcyclohexyl) piperazines: mixed s and human Δ₈-Δ₇ sterol isomerase ligands with antiproliferative and p-glycoprotein inhibitory activity, ChemMedChem 6 (2011) 73-80.
11. [11]
  [11] W.H. Liu, J.X. Chang, Y. Liu, J.W. Luo, J.W. Zhang, Design, synthesis and activities of novel benzothiazole derivatives containing arylpiperazine, Acta Pharmaceut. Sin. 48 (2013) 1259-1265.
12. [12]
  [12] M. Dellabella, G. Milanese, G. Muzzonigro, Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones, J. Urol. 170 (2003) 2202-2205.
13. [13]
  [13] T. Morita, I. Wada, H. Saeki, S. Tsuchida, R.M. Weiss, Ureteral urine transport: changes in bolus volume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs, J. Urol. 137 (1987) 132-135.
14. [14]
  [14] Y. Nishino, T. Masue, K. Miwa, et al., Comparison of two α1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study, BJU Int. 97 (2006) 747-751.
15. [15]
  [15] Y. Kojima, S. Sasaki, Y. Kubota, et al., Expression of α1-adrenoceptor subtype mRNA as a predictor of the efficacy of subtype selective α1-adrenoceptor antagonists in the management of benign prostatic hyperplasia, J. Urol. 179 (2008) 1040-1046.
16. [16]
  [16] Y. Hori, K. Ishii, H. Kanda, et al., Naftopidil, a selective α1-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma, Cancer Prev. Res. 4 (2011) 87-96.
17. [17]
  [17] H. Kanda, K. Ishii, Y. Ogura, et al., Naftopidil, a selective α-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest, Int. J. Cancer 122 (2008) 444-451.
18. [18]
  [18] E. Masachika, T. Kanno, T. Nakano, A. Gotoh, T. Nishizaki, Naftopidil induces apoptosis in malignant mesothelioma cell lines independently of α1-adrenoceptor blocking, Anticancer Res. 33 (2013) 887-894.
19. [19]
  [19] H. Chen, X. Liang, F. Xu, et al., Synthesis and cytotoxic activity evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines, Molecules 19 (2014) 12048-12064.
20. [20]
  [20] H. Chen, F. Xu, X. Liang, et al., Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines, Bioorg. Med. Chem. Lett. 25 (2015) 285-287.
21. [21]
  [21] G.J.L. Kaspers, A.J. Veerman, R. Pieters, et al., In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia, Blood 90 (1997) 2723-2729.
22. [22]
  [22] G.J.L. Kaspers, R. Pieters, C.H. Van Zantwijk, et al., Prednisolone resistance in childhood acute lymphoblastic leukemia: vitro-vivo correlations and cross-resistance to other drugs, Blood 92 (1998) 259-266.
23. [23]
  [23] J. Ding, S.L. Huang, S.Q. Wu, et al., Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA, Nat. Cell Biol. 12 (2010) 390-399.
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