Nitrogen-containing Derivatives of O-tetramethylquercetin: Synthesis and Biological Profiles in Prostate Cancer Cell Models

Overview

Journal Bioorg Chem

Publisher Elsevier

Specialties Biochemistry
Chemistry

Date 2019 Mar 25

PMID 30904813

Citations 6

Authors

Pravien Rajaram

Ziran Jiang

Guanglin Chen

Alyssa Rivera

Alison Phasakda

Qiang Zhang

Shilong Zheng

Guangdi Wang

Qiao-Hong Chen

Affiliations

Soon will be listed here.

Abstract

Forty-eight nitrogen-containing quercetin derivatives were synthesized from readily available rutin or quercetin for the in vitro evaluation of their biological profiles. The WST-1 cell proliferation assay data indicate that thirty-nine out of the forty-eight derivatives possess significantly improved antiproliferative potency as compared with quercetin and fisetin, as well as the parent 3,3',4',7-O-tetramethylquercetin toward both androgen-sensitive (LNCaP) and androgen-insensitive (PC-3 and DU145) human prostate cancer cell lines. 5-O-Aminoalkyl-3,3',4',7-O-tetramethylquercetins were established as a better scaffold for further development as anti-prostate cancer agents. Among them, 5-O-(N,N-dibutylamino)propyl-3,3',4',7-O-tetramethylquercetin (44) was identified as the optimal derivative with IC values of 0.55-2.82 µM, being over 35-182 times more potent than quercetin. The flow cytometry-based assays further demonstrate that 44 effectively activates PC-3 cell apoptosis.

Citing Articles

5-Substituted Flavones-Another Class of Potent Triplex DNA-Specific Ligands as Antigene Enhancers.

Gu L, Tran N, Rangel V, Singh M, Christison K, Lin-Cereghino G Molecules. 2025; 29(24.

PMID: 39769951 PMC: 11678237. DOI: 10.3390/molecules29245862.

Design, Synthesis and Antitumor Activity of Quercetin Derivatives Containing a Quinoline Moiety.

Zhang W, Sun J, Zhang P, Yue R, Zhang Y, Niu F Molecules. 2024; 29(1).

PMID: 38202823 PMC: 10780609. DOI: 10.3390/molecules29010240.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Chaudhary M, Kumar S, Kaur P, Sahu S, Mittal A Mini Rev Med Chem. 2023; 24(7):721-747.

PMID: 37694781 DOI: 10.2174/1389557523666230911141339.

Synthesis of new flavonoid derivatives based on 3-hydroxy-4'-dimethylamino flavone and study the activity of some of them as antifungal.

Khdera H, Saad S, Moustapha A, Kandil F Heliyon. 2022; 8(12):e12062.

PMID: 36561670 PMC: 9763748. DOI: 10.1016/j.heliyon.2022.e12062.

A Review of the Pharmacological Potential of Dunn on Cancer.

Zhang F, Ganesan K, Liu Q, Chen J Cells. 2022; 11(18).

PMID: 36139460 PMC: 9497142. DOI: 10.3390/cells11182885.

References

Shoskes D, Zeitlin S, Shahed A, Rajfer J . Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology. 1999; 54(6):960-3. DOI: 10.1016/s0090-4295(99)00358-1. View

Manthey J, Guthrie N . Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J Agric Food Chem. 2002; 50(21):5837-43. DOI: 10.1021/jf020121d. View

Sampson L, Rimm E, Hollman P, de Vries J, Katan M . Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002; 102(10):1414-20. DOI: 10.1016/s0002-8223(02)90314-7. View

Shenouda N, Zhou C, Browning J, Ansell P, Sakla M, Lubahn D . Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer. 2004; 49(2):200-8. DOI: 10.1207/s15327914nc4902_12. View

Vijayababu M, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas M, Arunakaran J . Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol. 2005; 131(11):765-71. DOI: 10.1007/s00432-005-0005-4. View

McCann S, Ambrosone C, Moysich K, Brasure J, Marshall J, Freudenheim J . Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in western New York. Nutr Cancer. 2005; 53(1):33-41. DOI: 10.1207/s15327914nc5301_4. View

Hedelin M, Klint A, Chang E, Bellocco R, Johansson J, Andersson S . Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden). Cancer Causes Control. 2006; 17(2):169-80. DOI: 10.1007/s10552-005-0342-2. View

Bosetti C, Bravi F, Talamini R, Parpinel M, Gnagnarella P, Negri E . Flavonoids and prostate cancer risk: a study in Italy. Nutr Cancer. 2007; 56(2):123-7. DOI: 10.1207/s15327914nc5602_1. View

Utesch D, Feige K, Dasenbrock J, Broschard T, Harwood M, Danielewska-Nikiel B . Evaluation of the potential in vivo genotoxicity of quercetin. Mutat Res. 2008; 654(1):38-44. DOI: 10.1016/j.mrgentox.2008.04.008. View

10.

Aalinkeel R, Bindukumar B, Reynolds J, Sykes D, Mahajan S, Chadha K . The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90. Prostate. 2008; 68(16):1773-89. PMC: 2826114. DOI: 10.1002/pros.20845. View

11.

Nguyen T, Nguyen K, Kamounah F, Zhang W, Hansen P . NMR of a series of novel hydroxyflavothiones. Magn Reson Chem. 2009; 47(12):1043-54. DOI: 10.1002/mrc.2510. View

12.

Liu H, Jiang W, Xie M . Flavonoids: recent advances as anticancer drugs. Recent Pat Anticancer Drug Discov. 2010; 5(2):152-64. DOI: 10.2174/157489210790936261. View

13.

Slusarz A, Shenouda N, Sakla M, Drenkhahn S, Narula A, MacDonald R . Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res. 2010; 70(8):3382-90. DOI: 10.1158/0008-5472.CAN-09-3012. View

14.

ONeill A, Prencipe M, Dowling C, Fan Y, Mulrane L, Gallagher W . Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. Mol Cancer. 2011; 10:126. PMC: 3203088. DOI: 10.1186/1476-4598-10-126. View

15.

Wang P, Heber D, Henning S . Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Nutr Cancer. 2012; 64(4):580-7. PMC: 3363324. DOI: 10.1080/01635581.2012.661514. View

16.

Pratheeshkumar P, Budhraja A, Son Y, Wang X, Zhang Z, Ding S . Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways. PLoS One. 2012; 7(10):e47516. PMC: 3475699. DOI: 10.1371/journal.pone.0047516. View

17.

Cialdella-Kam L, Nieman D, Sha W, Meaney M, Knab A, Shanely R . Dose-response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults. Br J Nutr. 2012; 109(11):1923-33. DOI: 10.1017/S0007114512003972. View

18.

Xu R, Zhang Y, Ye X, Xue S, Shi J, Pan J . Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro. Food Chem. 2012; 138(1):48-53. DOI: 10.1016/j.foodchem.2012.09.102. View

19.

Wang G, Song L, Wang H, Xing N . Quercetin synergizes with 2-methoxyestradiol inhibiting cell growth and inducing apoptosis in human prostate cancer cells. Oncol Rep. 2013; 30(1):357-63. DOI: 10.3892/or.2013.2469. View

20.

Geybels M, Verhage B, Arts I, van Schooten F, Goldbohm R, van den Brandt P . Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer. Am J Epidemiol. 2013; 177(12):1388-98. DOI: 10.1093/aje/kws419. View