Chiral Flavonoids as Antitumor Agents
Abstract
:1. Introduction
2. Flavonoids
2.1. Natural Chiral Flavonoids with Antitumor Activity
2.2. Synthetic Chiral Flavonoids with Antitumor Activity
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
- Kopustinskiene, D.M.; Jakstas, V.; Savickas, A.; Bernatoniene, J. Flavonoids as Anticancer Agents. Nutrients 2020, 12, 457. [Google Scholar] [CrossRef] [Green Version]
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef]
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Vasan, N.; Baselga, J.; Hyman, D.M. A view on drug resistance in cancer. Nature 2019, 575, 299–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abotaleb, M.; Samuel, S.M.; Varghese, E.; Varghese, S.; Kubatka, P.; Liskova, A.; Büsselberg, D. Flavonoids in Cancer and Apoptosis. Cancers 2018, 11, 28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kinghorn, A.D.; Chin, Y.-W.; Swanson, S.M. Discovery of natural product anticancer agents from biodiverse organisms. Curr. Opin. Drug Discov. Dev. 2009, 12, 189–196. [Google Scholar]
- Agrawal, A. Pharmacological Activities of Flavonoids: A Review. Int. J. Pharm. Sci. Nanotechnol. 2011, 4, 1394–1398. [Google Scholar] [CrossRef]
- Patil, V.M.; Masand, N. Chapter 12—Anticancer Potential of Flavonoids: Chemistry, Biological Activities, and Future Perspectives. In Studies in Natural Products Chemistry; Atta-ur, R., Ed.; Elsevier: Amsterdam, The Netherlands, 2018; pp. 401–430. [Google Scholar]
- Xiang, Y.; Liu, S.; Yang, J.; Wang, Z.; Zhang, H.; Gui, C. Investigation of the interactions between flavonoids and human organic anion transporting polypeptide 1B1 using fluorescent substrate and 3D-QSAR analysis. Biochim. Biophys. Acta Biomembr. 2020, 1862, 183210. [Google Scholar] [CrossRef]
- Martins, B.T.; Correia da Silva, M.; Pinto, M.; Cidade, H.; Kijjoa, A. Marine natural flavonoids: Chemistry and biological activities. Nat. Prod. Res. 2019, 33, 3260–3272. [Google Scholar] [CrossRef]
- Mutha, R.E.; Tatiya, A.U.; Surana, S.J. Flavonoids as natural phenolic compounds and their role in therapeutics: An overview. Future J. Pharm. Sci. 2021, 7, 25. [Google Scholar] [CrossRef] [PubMed]
- Guo, J.; Zhou, X.; Wang, T.; Wang, G.; Cao, F. Regulation of flavonoid metabolism in ginkgo leaves in response to different day-night temperature combinations. Plant Physiol. Biochem. 2020, 147, 133–140. [Google Scholar] [CrossRef] [PubMed]
- Pastore, C.; Dal Santo, S.; Zenoni, S.; Movahed, N.; Allegro, G.; Valentini, G.; Filippetti, I.; Tornielli, G.B. Whole Plant Temperature Manipulation Affects Flavonoid Metabolism and the Transcriptome of Grapevine Berries. Front. Plant Sci. 2017, 8, 929. [Google Scholar] [CrossRef]
- Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci. 2016, 5, e47. [Google Scholar] [CrossRef] [Green Version]
- Ren, F.; Nian, Y.; Perussello, C.A. Effect of storage, food processing and novel extraction technologies on onions flavonoid content: A review. Food Res. Int. 2019, 132, 108953. [Google Scholar] [CrossRef] [PubMed]
- Tuenter, E.; Creylman, J.; Verheyen, G.; Pieters, L.; Van Miert, S. Development of a classification model for the antigenotoxic activity of flavonoids. Bioorganic Chem. 2020, 98, 103705. [Google Scholar] [CrossRef]
- Miadoková, E. Isoflavonoids—An overview of their biological activities and potential health benefits. Interdiscip. Toxicol. 2009, 2, 211–218. [Google Scholar] [CrossRef]
- Silva, L.; Shahidi, F.; Coimbra, M.A. Dried Fruits Phytochemicals and Health Effects; John Wiley & Sons: Oxford, UK, 2013. [Google Scholar]
- Křížová, L.; Dadáková, K.; Kašparovská, J.; Kašparovský, T. Isoflavones. Molecules 2019, 24, 1076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tungmunnithum, D.; Thongboonyou, A.; Pholboon, A.; Yangsabai, A. Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview. Medicines 2018, 5, 93. [Google Scholar] [CrossRef] [PubMed]
- Ullah, A.; Munir, S.; Badshah, S.L.; Khan, N.; Ghani, L.; Poulson, B.G.; Emwas, A.-H.; Jaremko, M. Important Flavonoids and Their Role as a Therapeutic Agent. Molecules 2020, 25, 5243. [Google Scholar] [CrossRef] [PubMed]
- Waheed Janabi, A.H.; Kamboh, A.A.; Saeed, M.; Lu, X.; BiBi, J.; Majeed, F.; Naveed, M.; Mughal, M.J.; Korejo, N.A.; Kamboh, R.; et al. Flavonoid-rich foods (FRF): A promising nutraceutical approach against lifespan-shortening diseases. Iran. J. Basic Med. Sci. 2020, 23, 140–153. [Google Scholar]
- Valavanidis, A.; Vlachogianni, T. Chapter 8—Plant Polyphenols: Recent Advances in Epidemiological Research and Other Studies on Cancer Prevention. In Studies in Natural Products Chemistry; Atta-ur, R., Ed.; Elsevier: Amsterdam, The Netherlands, 2013; pp. 269–295. [Google Scholar]
- Alseekh, S.; Perez de Souza, L.; Benina, M.; Fernie, A.R. The style and substance of plant flavonoid decoration; towards defining both structure and function. Phytochemistry 2020, 174, 112347. [Google Scholar] [CrossRef] [PubMed]
- Treml, J.; Šmejkal, K. Flavonoids as Potent Scavengers of Hydroxyl Radicals. Compr. Rev. Food Sci. Food Saf. 2016, 15, 720–738. [Google Scholar] [CrossRef]
- Rehman, M.U.; Tahir, M.; Khan, A.Q.; Khan, R.; Lateef, A.; Oday, O.H.; Qamar, W.; Ali, F.; Sultana, S. Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: Plausible role of NF-κB. Toxicol. Lett. 2013, 216, 146–158. [Google Scholar] [CrossRef]
- Forni, C.; Rossi, M.; Borromeo, I.; Feriotto, G.; Platamone, G.; Tabolacci, C.; Mischiati, C.; Beninati, S. Flavonoids: A Myth or a Reality for Cancer Therapy? Molecules 2021, 26, 3583. [Google Scholar] [CrossRef]
- Zhao, J.; Yang, J.; Xie, Y. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. Int. J. Pharm. 2019, 570, 118642. [Google Scholar] [CrossRef] [PubMed]
- Duodu, K.G.; Awika, J.M. Chapter 8—Phytochemical-Related Health-Promoting Attributes of Sorghum and Millets. In Sorghum and Millets, 2nd ed.; Taylor, J.R.N., Duodu, K.G., Eds.; AACC International Press: Washington, DC, USA, 2019; pp. 225–258. [Google Scholar]
- Cirmi, S.; Ferlazzo, N.; Lombardo, G.E.; Maugeri, A.; Calapai, G.; Gangemi, S.; Navarra, M. Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives? Nutrients 2016, 8, 698. [Google Scholar] [CrossRef] [Green Version]
- Brand, W.; Shao, J.; Hoek-van den Hil, E.F.; van Elk, K.N.; Spenkelink, B.; de Haan, L.H.; Rein, M.J.; Dionisi, F.; Williamson, G.; van Bladeren, P.J.; et al. Stereoselective conjugation, transport and bioactivity of s- and R-hesperetin enantiomers in vitro. J. Agric. Food Chem. 2010, 58, 6119–6125. [Google Scholar] [CrossRef]
- Curti, V.; Di Lorenzo, A.; Rossi, D.; Martino, E.; Capelli, E.; Collina, S.; Daglia, M. Enantioselective Modulatory Effects of Naringenin Enantiomers on the Expression Levels of miR-17-3p Involved in Endogenous Antioxidant Defenses. Nutrients 2017, 9, 215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, J.; Lee, D.-H.; Jang, H.; Park, S.-Y.; Seol, J.-W. Naringenin exerts anticancer effects by inducing tumor cell death and inhibiting angiogenesis in malignant melanoma. Int. J. Med. Sci. 2020, 17, 3049–3057. [Google Scholar] [CrossRef] [PubMed]
- Arul, D.; Subramanian, P. Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol. Oncol. Res. 2013, 19, 763–770. [Google Scholar] [CrossRef]
- Bao, L.; Liu, F.; Guo, H.B.; Li, Y.; Tan, B.B.; Zhang, W.X.; Peng, Y.H. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumour Biol. 2016, 37, 11365–11374. [Google Scholar] [CrossRef]
- Chang, H.-L.; Chang, Y.-M.; Lai, S.-C.; Chen, K.-M.; Wang, K.-C.; Chiu, T.-T.; Chang, F.-H.; Hsu, L.-S. Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and -9. Exp. Ther. Med. 2017, 13, 739–744. [Google Scholar] [CrossRef] [Green Version]
- Devi, K.P.; Rajavel, T.; Nabavi, S.F.; Setzer, W.N.; Ahmadi, A.; Mansouri, K.; Nabavi, S.M. Hesperidin: A promising anticancer agent from nature. Ind. Crop. Prod. 2015, 76, 582–589. [Google Scholar] [CrossRef]
- Erdem Guzel, E.; Tektemur, N.K. Hesperetin may alleviate the development of doxorubicin-induced pulmonary toxicity by decreasing oxidative stress and apoptosis in male rats. Tissue Cell 2021, 73, 101667. [Google Scholar] [CrossRef]
- Ferreira de Oliveira, J.M.P.; Santos, C.; Fernandes, E. Therapeutic potential of hesperidin and its aglycone hesperetin: Cell cycle regulation and apoptosis induction in cancer models. Phytomedicine 2020, 73, 152887. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Zhang, Y.; Li, Y.; Zhang, L.; Yu, S. Preclinical Investigation of Alpinetin in the Treatment of Cancer-Induced Cachexia via Activating PPARγ. Front. Pharmacol. 2021, 12, 687491. [Google Scholar] [CrossRef]
- Zhao, X.; Guo, X.; Shen, J.; Hua, D. Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling. Mol. Med. Rep. 2018, 18, 4030–4036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Du, J.; Tang, B.; Wang, J.; Sui, H.; Jin, X.; Wang, L.; Wang, Z. Antiproliferative effect of alpinetin in BxPC-3 pancreatic cancer cells. Int. J. Mol. Med. 2012, 29, 607–612. [Google Scholar] [CrossRef] [Green Version]
- Zhang, T.; Guo, S.; Zhu, X.; Qiu, J.; Deng, G.; Qiu, C. Alpinetin inhibits breast cancer growth by ROS/NF-κB/HIF-1α axis. J. Cell. Mol. Med. 2020, 24, 8430–8440. [Google Scholar] [CrossRef] [PubMed]
- Saquib, Q.; Ahmed, S.; Ahmad, M.S.; Al-Rehaily, A.J.; Siddiqui, M.A.; Faisal, M.; Ahmad, J.; Alsaleh, A.N.; Alatar, A.A.; Al-Khedhairy, A.A. Anticancer efficacies of persicogenin and homoeriodictyol isolated from Rhus retinorrhoea. Process Biochem. 2020, 95, 186–196. [Google Scholar] [CrossRef]
- Li, W.X.; Cui, C.B.; Cai, B.; Wang, H.Y.; Yao, X.S. Flavonoids from Vitex trifolia L. inhibit cell cycle progression at G2/M phase and induce apoptosis in mammalian cancer cells. J. Asian Nat. Prod. Res. 2005, 7, 615–626. [Google Scholar] [CrossRef]
- Suksamrarn, A.; Chotipong, A.; Suavansri, T.; Boongird, S.; Timsuksai, P.; Vimuttipong, P.; Chuaynugul, A. Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of Chromolaena odorata. Arch. Pharm. Res. 2004, 27, 507–511. [Google Scholar] [CrossRef]
- Han, N.; Huang, T.; Wang, Y.C.; Yin, J.; Kadota, S. Flavanone glycosides from Viscum coloratum and their inhibitory effects on osteoclast formation. Chem. Biodivers. 2011, 8, 1682–1688. [Google Scholar] [CrossRef]
- Singhal, S.S.; Singhal, S.; Singhal, P.; Singhal, J.; Horne, D.; Awasthi, S. Didymin: An orally active citrus flavonoid for targeting neuroblastoma. Oncotarget 2017, 8, 29428–29441. [Google Scholar] [CrossRef] [Green Version]
- Hung, J.-Y.; Hsu, Y.-L.; Ko, Y.-C.; Tsai, Y.-M.; Yang, C.-J.; Huang, M.-S.; Kuo, P.-L. Didymin, a dietary flavonoid glycoside from citrus fruits, induces Fas-mediated apoptotic pathway in human non-small-cell lung cancer cells in vitro and in vivo. Lung Cancer 2010, 68, 366–374. [Google Scholar] [CrossRef]
- Yao, Q.; Lin, M.T.; Zhu, Y.D.; Xu, H.L.; Zhao, Y.Z. Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin. Molecules 2018, 23, 2547. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsu, Y.L.; Hsieh, C.J.; Tsai, E.M.; Hung, J.Y.; Chang, W.A.; Hou, M.F.; Kuo, P.L. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment. Oncol. Lett. 2016, 11, 1035–1042. [Google Scholar] [CrossRef] [Green Version]
- Babaei, F.; Moafizad, A.; Darvishvand, Z.; Mirzababaei, M.; Hosseinzadeh, H.; Nassiri-Asl, M. Review of the effects of vitexin in oxidative stress-related diseases. Food Sci. Nutr. 2020, 8, 2569–2580. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, X.; Jiang, Q.; Liu, H.; Luo, S. Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells. Biol. Res. 2019, 52, 7. [Google Scholar] [CrossRef] [PubMed]
- Bhardwaj, M.; Cho, H.J.; Paul, S.; Jakhar, R.; Khan, I.; Lee, S.-J.; Kim, B.-Y.; Krishnan, M.; Khaket, T.P.; Lee, H.G.; et al. Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells. Oncotarget 2017, 9, 3278–3291. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tao, Y.; Zhan, S.; Wang, Y.; Zhou, G.; Liang, H.; Chen, X.; Shen, H. Baicalin, the major component of traditional Chinese medicine Scutellaria baicalensis induces colon cancer cell apoptosis through inhibition of oncomiRNAs. Sci. Rep. 2018, 8, 14477. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gong, W.; Zhao, Z.; Liu, B.; Lu, L.; Dong, J. Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors. Eur. J. Med. Chem. 2017, 126, 844–852. [Google Scholar] [CrossRef] [PubMed]
- Singh, S.; Meena, A.; Luqman, S. Baicalin mediated regulation of key signaling pathways in cancer. Pharmacol. Res. 2021, 164, 105387. [Google Scholar] [CrossRef]
- Wang, N.; Tang, L.J.; Zhu, G.Q.; Peng, D.Y.; Wang, L.; Sun, F.N.; Li, Q.L. Apoptosis induced by baicalin involving up-regulation of P53 and bax in MCF-7 cells. J. Asian Nat. Prod. Res. 2008, 10, 1129–1135. [Google Scholar] [CrossRef]
- Wan, D.; Ouyang, H. Baicalin induces apoptosis in human osteosarcoma cell through ROS-mediated mitochondrial pathway. Nat. Prod. Res. 2018, 32, 1996–2000. [Google Scholar] [CrossRef]
- Sui, X.; Han, X.; Chen, P.; Wu, Q.; Feng, J.; Duan, T.; Chen, X.; Pan, T.; Yan, L.; Jin, T.; et al. Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway. Front. Mol. Biosci. 2021, 7, 602282. [Google Scholar] [CrossRef] [PubMed]
- Yang, B.; Bai, H.; Sa, Y.; Zhu, P.; Liu, P. Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells. J. Cancer 2020, 11, 2303–2317. [Google Scholar] [CrossRef]
- Yano, H.; Mizoguchi, A.; Fukuda, K.; Haramaki, M.; Ogasawara, S.; Momosaki, S.; Kojiro, M. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res. 1994, 54, 448–454. [Google Scholar] [PubMed]
- Shi, J.; Wu, G.; Zou, X.; Jiang, K. Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats. Cardiorenal Med. 2019, 9, 31–40. [Google Scholar] [CrossRef] [PubMed]
- Ohkoshi, E.; Umemura, N. Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells. Int. J. Oncol. 2017, 50, 387–395. [Google Scholar] [CrossRef] [Green Version]
- Yu, Y.; Pei, M.; Li, L. Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo. Int. J. Clin. Exp. Med. 2015, 8, 8958–8967. [Google Scholar]
- Chen, J.; Li, Z.; Chen, A.Y.; Ye, X.; Luo, H.; Rankin, G.O.; Chen, Y.C. Inhibitory effect of baicalin and baicalein on ovarian cancer cells. Int. J. Mol. Sci. 2013, 14, 6012–6025. [Google Scholar] [CrossRef] [Green Version]
- Yang, C.S.; Wang, H. Cancer Preventive Activities of Tea Catechins. Molecules 2016, 21, 1679. [Google Scholar] [CrossRef]
- George, V.C.; Dellaire, G.; Rupasinghe, H.P.V. Plant flavonoids in cancer chemoprevention: Role in genome stability. J. Nutr. Biochem. 2017, 45, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Min, K.-J.; Kwon, T.K. Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate. Integr. Med. Res. 2014, 3, 16–24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pojero, F.; Poma, P.; Spanò, V.; Montalbano, A.; Barraja, P.; Notarbartolo, M. Targeting multiple myeloma with natural polyphenols. Eur. J. Med. Chem. 2019, 180, 465–485. [Google Scholar] [CrossRef] [PubMed]
- Chen, B.-H.; Hsieh, C.-H.; Tsai, S.-Y.; Wang, C.-Y.; Wang, C.-C. Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway. Sci. Rep. 2020, 10, 5163. [Google Scholar] [CrossRef] [Green Version]
- Bae, J.; Kumazoe, M.; Yamashita, S.; Tachibana, H. Hydrogen sulphide donors selectively potentiate a green tea polyphenol EGCG-induced apoptosis of multiple myeloma cells. Sci. Rep. 2017, 7, 6665. [Google Scholar] [CrossRef]
- James, K.D.; Kennett, M.J.; Lambert, J.D. Potential role of the mitochondria as a target for the hepatotoxic effects of (−)-epigallocatechin-3-gallate in mice. Food Chem. Toxicol. 2018, 111, 302–309. [Google Scholar] [CrossRef] [PubMed]
- Md Nesran, Z.N.; Shafie, N.H.; Md Tohid, S.F.; Norhaizan, M.E.; Ismail, A. Iron Chelation Properties of Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking. Evid.-Based Complementary Altern. Med. 2020, 2020, 7958041. [Google Scholar] [CrossRef] [Green Version]
- Tsai, Y.-J.; Chen, B.-H. Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3. Int. J. Nanomed. 2016, 11, 1907–1926. [Google Scholar]
- Li, J.; Hu, L.; Zhou, T.; Gong, X.; Jiang, R.; Li, H.; Kuang, G.; Wan, J.; Li, H. Taxifolin inhibits breast cancer cells proliferation, migration and invasion by promoting mesenchymal to epithelial transition via β-catenin signaling. Life Sci. 2019, 232, 116617. [Google Scholar] [CrossRef]
- Razak, S.; Afsar, T.; Ullah, A.; Almajwal, A.; Alkholief, M.; Alshamsan, A.; Jahan, S. Taxifolin, a natural flavonoid interacts with cell cycle regulators causes cell cycle arrest and causes tumor regression by activating Wnt/β-catenin signaling pathway. BMC Cancer 2018, 18, 1043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, R.; Zhu, X.; Wang, Q.; Li, X.; Wang, E.; Zhao, Q.; Wang, Q.; Cao, H. The anti-tumor effect of taxifolin on lung cancer via suppressing stemness and epithelial-mesenchymal transition in vitro and oncogenesis in nude mice. Ann. Transl. Med. 2020, 8, 590. [Google Scholar] [CrossRef]
- Yang, C.-L.; Lin, Y.-S.; Liu, K.-F.; Peng, W.-H.; Hsu, C.-M. Hepatoprotective Mechanisms of Taxifolin on Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Nutrients 2019, 11, 2655. [Google Scholar] [CrossRef] [Green Version]
- Butt, S.S.; Khan, K.; Badshah, Y.; Rafiq, M.; Shabbir, M. Evaluation of pro-apoptotic potential of taxifolin against liver cancer. PeerJ 2021, 9, e11276. [Google Scholar] [CrossRef]
- Bijak, M. Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)-Chemistry, Bioavailability, and Metabolism. Molecules 2017, 22, 1942. [Google Scholar] [CrossRef] [Green Version]
- Tuli, H.S.; Mittal, S.; Aggarwal, D.; Parashar, G.; Parashar, N.C.; Upadhyay, S.K.; Barwal, T.S.; Jain, A.; Kaur, G.; Savla, R.; et al. Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance. Semin. Cancer Biol. 2021, 73, 196–218. [Google Scholar] [CrossRef] [PubMed]
- Mukhtar, S.; Zeng, X.; Qamer, S.; Saad, M.; Mubarik, M.S.; Mahmoud, A.H.; Mohammed, O.B. Hepatoprotective activity of silymarin encapsulation against hepatic damage in albino rats. Saudi J. Biol. Sci. 2021, 28, 717–723. [Google Scholar] [CrossRef] [PubMed]
- Si, L.; Liu, W.; Hayashi, T.; Ji, Y.; Fu, J.; Nie, Y.; Mizuno, K.; Hattori, S.; Onodera, S.; Ikejima, T. Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment. Arch. Biochem. Biophys. 2019, 671, 42–51. [Google Scholar] [CrossRef] [PubMed]
- Prasad, R.R.; Paudel, S.; Raina, K.; Agarwal, R. Silibinin and non-melanoma skin cancers. J. Tradit. Complementary Med. 2020, 10, 236–244. [Google Scholar] [CrossRef]
- Sherman, B.; Hernandez, A.M.; Alhado, M.; Menge, L.; Price, R.S. Silibinin Differentially Decreases the Aggressive Cancer Phenotype in an In Vitro Model of Obesity and Prostate Cancer. Nutr. Cancer 2020, 72, 333–342. [Google Scholar] [CrossRef]
- Raina, K.; Kumar, S.; Dhar, D.; Agarwal, R. Silibinin and colorectal cancer chemoprevention: A comprehensive review on mechanisms and efficacy. J. Biomed. Res. 2016, 30, 452–465. [Google Scholar]
- Jahanafrooz, Z.; Motamed, N.; Rinner, B.; Mokhtarzadeh, A.; Baradaran, B. Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator. Life Sci. 2018, 213, 236–247. [Google Scholar] [CrossRef]
- Pashaei-Asl, F.; Pashaei-Asl, R.; Khodadadi, K.; Akbarzadeh, A.; Ebrahimie, E.; Pashaiasl, M. Enhancement of anticancer activity by silibinin and paclitaxel combination on the ovarian cancer. Artif. Cells Nanomed. Biotechnol. 2018, 46, 1483–1487. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Ge, Y.; Ping, X.; Yu, M.; Lou, D.; Shi, W. Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines. Mol. Med. Rep. 2018, 18, 1835–1841. [Google Scholar] [CrossRef]
- Li, W.G.; Wang, H.Q. Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study. J. Buon 2016, 21, 917–924. [Google Scholar] [PubMed]
- Bukowski, K.; Kciuk, M.; Kontek, R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci. 2020, 21, 3233. [Google Scholar] [CrossRef]
- Molavi, O.; Narimani, F.; Asiaee, F.; Sharifi, S.; Tarhriz, V.; Shayanfar, A.; Hejazi, M.; Lai, R. Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy. Pharm. Biol. 2017, 55, 729–739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Y.; Xie, X.; Hou, X.; Shen, J.; Shi, J.; Chen, H.; He, Y.; Wang, Z.; Feng, N. Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis. J. Nanobiotechnology 2020, 18, 83. [Google Scholar] [CrossRef]
- Lampe, J.W. Emerging research on equol and cancer. J. Nutr. 2010, 140, 1369S–1372S. [Google Scholar] [CrossRef] [Green Version]
- De la Parra, C.; Otero-Franqui, E.; Martinez-Montemayor, M.; Dharmawardhane, S. The soy isoflavone equol may increase cancer malignancy via up-regulation of eukaryotic protein synthesis initiation factor eIF4G. J. Biol. Chem. 2012, 287, 41640–41650. [Google Scholar] [CrossRef] [Green Version]
- Brown, N.M.; Belles, C.A.; Lindley, S.L.; Zimmer-Nechemias, L.D.; Zhao, X.; Witte, D.P.; Kim, M.-O.; Setchell, K.D.R. The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer. Carcinogenesis 2010, 31, 886–893. [Google Scholar] [CrossRef] [Green Version]
- Lund, T.D.; Blake, C.; Bu, L.; Hamaker, A.N.; Lephart, E.D. Equol an isoflavonoid: Potential for improved prostate health, in vitro and in vivo evidence. Reprod. Biol. Endocrinol. 2011, 9, 4. [Google Scholar] [CrossRef] [Green Version]
- Choi, E.J.; Kim, T. Equol induced apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 but not MCF-7 cells. Mol. Med. Rep. 2008, 1, 239–244. [Google Scholar]
- Choi, E.J.; Ahn, W.S.; Bae, S.M. Equol induces apoptosis through cytochrome c-mediated caspases cascade in human breast cancer MDA-MB-453 cells. Chem. Biol. Interact. 2009, 177, 7–11. [Google Scholar] [CrossRef] [PubMed]
- Setchell, K.D.; Clerici, C.; Lephart, E.D.; Cole, S.J.; Heenan, C.; Castellani, D.; Wolfe, B.E.; Nechemias-Zimmer, L.; Brown, N.M.; Lund, T.D.; et al. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am. J. Clin. Nutr. 2005, 81, 1072–1079. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheng, J.; Wu, F.-H.; Wang, P.; Ke, J.-P.; Wan, X.-C.; Qiu, M.-H.; Bao, G.-H. Flavoalkaloids with a Pyrrolidinone Ring from Chinese Ancient Cultivated Tea Xi-Gui. J. Agric. Food Chem. 2018, 66, 7948–7957. [Google Scholar] [CrossRef] [PubMed]
- Feng, L.; Zhang, Y.; Liu, Y.-C.; Liu, Y.; Luo, S.-H.; Huang, C.-S.; Li, S.-H. Leucoflavonine, a new bioactive racemic flavoalkaloid from the leaves of Leucosceptrum canum. Bioorganic Med. Chem. 2019, 27, 442–446. [Google Scholar] [CrossRef]
- Ur Rashid, M.; Alamzeb, M.; Ali, S.; Ullah, Z.; Shah, Z.A.; Naz, I.; Khan, M.R. The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review. Phytother. Res. 2019, 33, 2661–2684. [Google Scholar] [CrossRef] [PubMed]
- Jain, S.K.; Bharate, S.B.; Vishwakarma, R.A. Cyclin-dependent kinase inhibition by flavoalkaloids. Mini Rev. Med. Chem. 2012, 12, 632–649. [Google Scholar] [CrossRef] [PubMed]
- Beutler, J.A.; Cardellina, J.H., 2nd; McMahon, J.B.; Boyd, M.R.; Cragg, G.M. Anti-HIV and cytotoxic alkaloids from Buchenavia capitata. J. Nat. Prod. 1992, 55, 207–213. [Google Scholar] [CrossRef]
- Li, F.-F.; Sun, Q.; Wang, D.; Liu, S.; Lin, B.; Liu, C.-T.; Li, L.-Z.; Huang, X.-X.; Song, S.-J. Chiral Separation of Cytotoxic Flavan Derivatives from Daphne giraldii. J. Nat. Prod. 2016, 79, 2236–2242. [Google Scholar] [CrossRef]
- Andrushko, V.; Andrushko, N. Stereoselective Synthesis of Drugs and Natural Products; John Wiley & Sons: Hoboken, NJ, USA, 2013. [Google Scholar]
- Adly, F.G.; Ghanem, A.; Nag, A. Enantiomerically Pure Compounds by Enantioselective Synthetic Chiral Metal Complexes. In Asymmetric Synthesis of Drugs and Natural Products; CRC Press: Boca Raton, FL, USA, 2018; pp. 75–131. [Google Scholar]
- He, L.; Liang, Z.; Yu, G.; Li, X.; Chen, X.; Zhou, Z.; Ren, Z. Green and Efficient Resolution of Racemic Ofloxacin Using Tartaric Acid Derivatives via Forming Cocrystal in Aqueous Solution. Cryst. Growth Des. 2018, 18, 5008–5020. [Google Scholar] [CrossRef]
- Pinto, M.M.M.; Fernandes, C.; Tiritan, M.E. Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View. Molecules 2020, 25, 1931. [Google Scholar] [CrossRef] [PubMed]
- Yáñez, J.A.; Andrews, P.K.; Davies, N.M. Methods of analysis and separation of chiral flavonoids. J. Chromatogr. B 2007, 848, 159–181. [Google Scholar] [CrossRef]
- Lee, S.H.; Lee, K.R.; Cho, E.A.; Jung, S.H. Enantioseparation of Physiologically Active Some Flavonoids by Liquid Chromatography-Electrospray-Tandem Mass Spectrometry Based on Noncovalent Interactions with β-Cyclodextrin. Bull. Korean Chem. Soc. 2011, 32, 4415–4418. [Google Scholar] [CrossRef] [Green Version]
- Liu, L.-X.; Huang, W.-J.; Xie, Q.-X.; Wu, B.; Yu, C.-B.; Zhou, Y.-G. Dynamic Kinetic Resolution of Flavonoids via Asymmetric Allylic Alkylation: Construction of Two Contiguous Stereogenic Centers on Nucleophiles. Am. Chem. Soc. Catal. 2021, 11, 12859–12863. [Google Scholar] [CrossRef]
- Chen, Q.-H. Review of Classics in Stereoselective Synthesis. J. Nat. Prod. 2011, 74, 1670. [Google Scholar] [CrossRef]
- Ji, J.; Mould, D.R.; Blum, K.A.; Ruppert, A.S.; Poi, M.; Zhao, Y.; Johnson, A.J.; Byrd, J.C.; Grever, M.R.; Phelps, M.A. A pharmacokinetic/pharmacodynamic model of tumor lysis syndrome in chronic lymphocytic leukemia patients treated with flavopiridol. Clin. Cancer Res. 2013, 19, 1269–1280. [Google Scholar] [CrossRef] [Green Version]
- Pajtás, D.; Kónya, K.; Kiss-Szikszai, A.; Džubák, P.; Pethő, Z.; Varga, Z.; Panyi, G.; Patonay, T. Optimization of the Synthesis of Flavone–Amino Acid and Flavone–Dipeptide Hybrids via Buchwald–Hartwig Reaction. J. Org. Chem. 2017, 82, 4578–4587. [Google Scholar] [CrossRef]
- Ibrahim, N.; Bonnet, P.; Brion, J.-D.; Peyrat, J.-F.; Bignon, J.; Levaique, H.; Josselin, B.; Robert, T.; Colas, P.; Bach, S.; et al. Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency. Eur. J. Med. Chem. 2020, 199, 112355. [Google Scholar] [CrossRef]
- Bisol, Â.; de Campos, P.S.; Lamers, M.L. Flavonoids as anticancer therapies: A systematic review of clinical trials. Phytother. Res. 2020, 34, 568–582. [Google Scholar] [CrossRef]
- Zocchi, L.; Wu, S.C.; Wu, J.; Hayama, K.L.; Benavente, C.A. The cyclin-dependent kinase inhibitor flavopiridol (alvocidib) inhibits metastasis of human osteosarcoma cells. Oncotarget 2018, 9, 23505–23518. [Google Scholar] [CrossRef] [Green Version]
- Cassaday, R.D.; Goy, A.; Advani, S.; Chawla, P.; Nachankar, R.; Gandhi, M.; Gopal, A.K. A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. Clin. Lymphoma Myeloma Leuk. 2015, 15, 392–397. [Google Scholar] [CrossRef] [Green Version]
- Ray, B.; Mehrotra, R. Nucleic acid binding mechanism of flavone derivative, riviciclib: Structural analysis to unveil anticancer potential. J. Photochem. Photobiol. B Biol. 2020, 211, 111990. [Google Scholar] [CrossRef]
- Joshi, K.S.; Rathos, M.J.; Joshi, R.D.; Sivakumar, M.; Mascarenhas, M.; Kamble, S.; Lal, B.; Sharma, S. In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. Mol. Cancer Ther. 2007, 6, 918–925. [Google Scholar] [CrossRef] [Green Version]
- Galijatovic, A.; Otake, Y.; Walle, U.K.; Walle, T. Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells—Potential role in carcinogen bioinactivation. Pharm. Res. 2001, 18, 374–379. [Google Scholar] [CrossRef] [PubMed]
- Zhong, X.; Liu, D.; Jiang, Z.; Li, C.; Chen, L.; Xia, Y.; Liu, D.; Yao, Q.; Wang, D. Chrysin Induced Cell Apoptosis and Inhibited Invasion Through Regulation of TET1 Expression in Gastric Cancer Cells. OncoTargets Ther. 2020, 13, 3277–3287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brechbuhl, H.M.; Kachadourian, R.; Min, E.; Chan, D.; Day, B.J. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: The role of glutathione. Toxicol. Appl. Pharmacol. 2012, 258, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zheng, Y.; Wu, Y.; Hu, B.; Tao, L.; Chen, X.; Hoffelt, D.; Hu, F. Chrysin Inhibits Melanoma Tumor Metastasis via Interfering with the FOXM1/β-Catenin Signaling. J. Agric. Food Chem. 2020, 68, 9358–9367. [Google Scholar]
- Samarghandian, S.; Afshari, J.T.; Davoodi, S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics 2011, 66, 1073–1079. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, M.S.; Halagowder, D.; Devaraj, S.N. Methylated chrysin induces co-ordinated attenuation of the canonical Wnt and NF-kB signaling pathway and upregulates apoptotic gene expression in the early hepatocarcinogenesis rat model. Chem.-Biol. Interact. 2011, 193, 12–21. [Google Scholar] [CrossRef] [PubMed]
- Phan, T.; Yu, X.-M.; Kunnimalaiyaan, M.; Chen, H. Antiproliferative Effect of Chrysin on Anaplastic Thyroid Cancer. J. Surg. Res. 2011, 170, 84–88. [Google Scholar] [CrossRef]
- Song, X.; Liu, Y.; Ma, J.; He, J.; Zheng, X.; Lei, X.; Jiang, G.; Zhang, L. Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells. Med. Chem. Res. 2015, 24, 1789–1798. [Google Scholar] [CrossRef]
- Liu, D.; Li, Y.; Shen, H.; Li, Y.; He, J.; Zhang, Q.; Liu, Y. Synthesis and anti-tumor activities of novel 7-O-amino acids chrysin derivatives. Chin. Herb. Med. 2018, 10, 323–330. [Google Scholar] [CrossRef]
- Xu, Q.; Deng, H.; Li, X.; Quan, Z.-S. Application of Amino Acids in the Structural Modification of Natural Products: A Review. Front. Chem. 2021, 9, 650569. [Google Scholar] [CrossRef]
- Liu, Y.-M.; Li, Y.; Liu, R.-F.; Xiao, J.; Zhou, B.-N.; Zhang, Q.-Z.; Song, J.-X. Synthesis, characterization and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and EGFR downregulation. J. Asian Nat. Prod. Res. 2019, 23, 39–54. [Google Scholar] [CrossRef]
- Nguyen, L.A.; He, H.; Pham-Huy, C. Chiral drugs: An overview. Int. J. Biomed. Sci. 2006, 2, 85–100. [Google Scholar]
- Brooks, W.H.; Guida, W.C.; Daniel, K.G. The significance of chirality in drug design and development. Curr. Top. Med. Chem. 2011, 11, 760–770. [Google Scholar] [CrossRef]
- Li, Y.; Yao, J.; Han, C.; Yang, J.; Chaudhry, M.T.; Wang, S.; Liu, H.; Yin, Y. Quercetin, Inflammation and Immunity. Nutrients 2016, 8, 167. [Google Scholar] [CrossRef]
- Xu, D.; Hu, M.J.; Wang, Y.Q.; Cui, Y.L. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules 2019, 24, 1123. [Google Scholar] [CrossRef] [Green Version]
- Vafadar, A.; Shabaninejad, Z.; Movahedpour, A.; Fallahi, F.; Taghavipour, M.; Ghasemi, Y.; Akbari, M.; Shafiee, A.; Hajighadimi, S.; Moradizarmehri, S.; et al. Quercetin and cancer: New insights into its therapeutic effects on ovarian cancer cells. Cell Biosci. 2020, 10, 32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parveen, S.; Tabassum, S.; Arjmand, F. Human Topoisomerase I mediated cytotoxicity profile of l-valine-quercetin diorganotin(IV) antitumor drug entities. J. Organomet. Chem. 2016, 823, 23–33. [Google Scholar] [CrossRef]
- Kim, M.K.; Choo, H.; Chong, Y. Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance. J. Med. Chem. 2014, 57, 7216–7233. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.K.; Kim, Y.; Choo, H.; Chong, Y. Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein. Bioorganic Med. Chem. 2017, 25, 1219–1226. [Google Scholar] [CrossRef]
- Arjmand, F. Tin Complexes, Antitumor Activity. In Encyclopedia of Metalloproteins; Kretsinger, R.H., Uversky, V.N., Permyakov, E.A., Eds.; Springer: New York, NY, USA, 2013; pp. 2224–2233. [Google Scholar]
- De Sousa, G.F.; Valdés-Martínez, J.; Pérez, G.E.; Toscano, R.A.; Abras, A.; Filgueiras, C.A.L. Heptacoordination in Organotin(IV) Complexes: Spectroscopic and Structural Studies of 2,6–Diacetylpyridine bis(thiosemicarbazone)di–n–butyltin(IV) Chloride Nitromethane Solvate, [nBu2Sn(H2daptsc)]Cl2•MeNO2 and of 2,6–Diacetylpyridine bis(semicarbazone)dimethyltin(IV) trans–Tetrachlorodimethylstannate(IV), [Me2Sn(H2dapsc)][Me2 SnCl4]. J. Braz. Chem. Soc. 2002, 13, 565–569. [Google Scholar]
- Ali, S.; Saira, S. Anticarcinogenicity and Toxicity of Organotin(IV) Complexes: A Review. Iran. J. Sci. Technol. Trans. A Sci. 2016, 42, 505–524. [Google Scholar] [CrossRef]
- Zhou, Q.; Yu, L.S.; Zeng, S. Stereoselectivity of chiral drug transport: A focus on enantiomer-transporter interaction. Drug Metab. Rev. 2014, 46, 283–290. [Google Scholar] [CrossRef]
- Hou, Y.; Pi, C.; Feng, X.; Wang, Y.; Fu, S.; Zhang, X.; Zhao, L.; Wei, Y. Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway. Mol. Ther. Oncolytics 2020, 19, 67–78. [Google Scholar] [CrossRef] [PubMed]
- Leung, W.-H.; Mak, W.-L.; Chan, E.; Lam, T.; Lee, W.-S.; Kwong, H.-L.; Yeung, L.-L. Palladium-based Kinetic Resolution of Racemic Tosylaziridines. Synlett 2002, 2002, 1688–1690. [Google Scholar] [CrossRef]
- Yang, Z.; Xiao, F.; Zhang, Y.; Wu, Z.; Zheng, X. Asymmetric Synthesis of Chiral Flavan-3-Ols. Nat. Prod. Res. 2019, 33, 2995–3010. [Google Scholar] [CrossRef]
- Heravi, M.M.; Lashaki, T.B.; Fattahi, B.; Zadsirjan, V. Application of asymmetric Sharpless aminohydroxylation in total synthesis of natural products and some synthetic complex bio-active molecules. RSC Adv. 2018, 8, 6634–6659. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Chan, T.H. Enantioselective synthesis of epigallocatechin-3-gallate (EGCG), the active polyphenol component from green tea. Org. Lett. 2001, 3, 739–741. [Google Scholar] [CrossRef]
- Rensburg, H.; Van Heerden, P.; Ferreira, D. Enantioselective synthesis of flavonoids. Part 3.1trans- and cis-Flavan-3-ol methyl ether acetates. J. Chem. Soc. Perkin Trans. 1997, 1, 3415–3422. [Google Scholar] [CrossRef]
- Anderson, J.C.; Headley, C.; Stapleton, P.D.; Taylor, P.W. Asymmetric total synthesis of B-ring modified (−)-epicatechin gallate analogues and their modulation of beta-lactam resistance in Staphylococcus aureus. Tetrahedron 2005, 61, 7703–7711. [Google Scholar] [CrossRef]
- Takashi, H.; Ken, O.; Keisuke, S. General and Convenient Approach to Flavan-3-ols: Stereoselective Synthesis of (−)-Gallocatechin. Chem. Lett. 2006, 35, 1006–1007. [Google Scholar]
- Liu, Y.; Li, X.; Lin, G.; Xiang, Z.; Xiang, J.; Zhao, M.; Chen, J.; Yang, Z. Synthesis of catechins via thiourea/AuCl3-catalyzed cycloalkylation of aryl epoxides. J. Org. Chem. 2008, 73, 4625–4629. [Google Scholar] [CrossRef]
- Ohmori, K.; Yano, T.; Suzuki, K. General synthesis of epi-series catechins and their 3-gallates: Reverse polarity strategy. Org. Biomol. Chem. 2010, 8, 2693–2696. [Google Scholar] [CrossRef] [PubMed]
- Stadlbauer, S.; Ohmori, K.; Hattori, F.; Suzuki, K. A new synthetic strategy for catechin-class polyphenols: Concise synthesis of (−)-epicatechin and its 3-O-gallate. Chem. Commun. 2012, 48, 8425–8427. [Google Scholar] [CrossRef] [PubMed]
- Abe, H.; Itaya, S.; Sasaki, K.; Kobayashi, T.; Ito, H. Enantioselective Total Synthesis of the Proposed Structure of Furan-Containing Polyketide. Chem. Pharm. Bull. 2016, 64, 772–777. [Google Scholar] [CrossRef] [Green Version]
- Hirooka, Y.; Nitta, M.; Furuta, T.; Kan, T. Efficient Synthesis of Optically Active Gallocatechin3-gallate Derivatives via 6-endo Cyclization. Synlett 2008, 2008, 3234–3238. [Google Scholar]
- Anderson, J.C.; Grounds, H.; Reeves, S.; Taylor, P.W. Improved synthesis of structural analogues of (−)-epicatechin gallate for modulation of staphylococcal β-lactam resistance. Tetrahedron 2014, 70, 3485–3490. [Google Scholar] [CrossRef] [Green Version]
- Charris, J.; Domínguez, J.; Lobo, G.; Riggione, F. Synthesis of some Thiochromone Derivatives and Activity Against Plasmodium falciparum In-vitro. Pharm. Pharmacol. Commun. 1999, 5, 107–110. [Google Scholar] [CrossRef]
- Meng, L.; Ngai, K.Y.; Chang, X.; Lin, Z.; Wang, J. Cu(I)-Catalyzed Enantioselective Alkynylation of Thiochromones. Org. Lett. 2020, 22, 1155–1159. [Google Scholar] [CrossRef] [PubMed]
- Kataoka, T.; Watanabe, S.-I.; Mori, E.; Kadomoto, R.; Tanimura, S.; Kohno, M. Synthesis and structure-activity relationships of thioflavone derivatives as specific inhibitors of the ERK-MAP kinase signaling pathway. Bioorg. Med. Chem. 2004, 12, 2397–2407. [Google Scholar] [CrossRef]
- Meng, L.; Jin, M.Y.; Wang, J. Rh-Catalyzed Conjugate Addition of Arylzinc Chlorides to Thiochromones: A Highly Enantioselective Pathway for Accessing Chiral Thioflavanones. Org. Lett. 2016, 18, 4986–4989. [Google Scholar] [CrossRef] [PubMed]
- Rani, N.; Bharti, S.; Krishnamurthy, B.; Bhatia, J.; Sharma, C.; Kamal, M.A.; Ojha, S.; Arya, D.S. Pharmacological Properties and Therapeutic Potential of Naringenin: A Citrus Flavonoid of Pharmaceutical Promise. Curr. Pharm. Des. 2016, 22, 4341–4359. [Google Scholar] [CrossRef]
- Wang, Z.; Lu, W.; Li, Y.; Tang, B. Alpinetin promotes Bax translocation, induces apoptosis through the mitochondrial pathway and arrests human gastric cancer cells at the G2/M phase. Mol. Med. Rep. 2013, 7, 915–920. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, T.; Zhang, A.; Kuang, G.; Gong, X.; Jiang, R.; Lin, D.; Li, J.; Li, H.; Zhang, X.; Wan, J.; et al. Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling. Oncol. Rep. 2017, 38, 3599–3607. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.-Y.; Chien, Y.-S.; Chiu, T.-H.; Huang, W.-W.; Lu, C.-C.; Chiang, J.-H.; Yang, J.-S. Apoptosis triggered by vitexin in U937 human leukemia cells via a mitochondrial signaling pathway. Oncol. Rep. 2012, 28, 1883–1888. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, G.; Li, D.; Chen, H.; Zhang, J.; Jin, X. Vitexin induces G2/M-phase arrest and apoptosis via Akt/mTOR signaling pathway in human glioblastoma cells. Mol. Med. Rep. 2018, 17, 4599–4604. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Zheng, X.; Zeng, G.; Zhou, Y.; Yuan, H. Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma. Int. J. Mol. Med. 2014, 33, 441–448. [Google Scholar] [CrossRef]
- Dou, J.; Wang, Z.; Ma, L.; Peng, B.; Mao, K.; Li, C.; Su, M.; Zhou, C.; Peng, G. Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence. Oncotarget 2018, 9, 20089–20102. [Google Scholar] [CrossRef] [PubMed]
- Chan, F.L.; Choi, H.L.; Chen, Z.Y.; Chan, P.S.F.; Huang, Y. Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett. 2000, 160, 219–228. [Google Scholar] [CrossRef]
- Yan, X.; Rui, X.; Zhang, K. Baicalein inhibits the invasion of gastric cancer cells by suppressing the activity of the p38 signaling pathway. Oncol. Rep. 2015, 33, 737–743. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.; Hong, Z.; Chen, P.; Wang, J.; Zhou, Y.; Huang, J. Baicalin inhibits growth and induces apoptosis of human osteosarcoma cells by suppressing the AKT pathway. Oncol. Lett. 2019, 18, 3188–3194. [Google Scholar] [CrossRef] [Green Version]
- Decker, R.H.; Dai, Y.; Grant, S. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway. Cell Death Differ. 2001, 8, 715–724. [Google Scholar] [CrossRef]
- Gojo, I.; Zhang, B.; Fenton, R.G. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. Clin. Cancer Res. 2002, 8, 3527–3538. [Google Scholar]
- Wu, T.; Qin, Z.; Tian, Y.; Wang, J.; Xu, C.; Li, Z.; Bian, J. Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update. J. Med. Chem. 2020, 63, 13228–13257. [Google Scholar] [CrossRef]
- Das, A.; Baidya, R.; Chakraborty, T.; Samanta, A.K.; Roy, S. Pharmacological basis and new insights of taxifolin: A comprehensive review. Biomed. Pharmacother. 2021, 142, 112004. [Google Scholar] [CrossRef]
- Shafiei, S.S.; Solati-Hashjin, M.; Samadikuchaksaraei, A.; Kalantarinejad, R.; Asadi-Eydivand, M.; Abu Osman, N.A. Epigallocatechin Gallate/Layered Double Hydroxide Nanohybrids: Preparation, Characterization, and In Vitro Anti-Tumor Study. PLoS ONE 2015, 10, e0136530. [Google Scholar] [CrossRef]
- Shimizu, M.; Deguchi, A.; Joe, A.K.; McKoy, J.F.; Moriwaki, H.; Weinstein, I.B. EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. J. Exp. Ther. Oncol. 2005, 5, 69–78. [Google Scholar]
- Rady, I.; Mohamed, H.; Rady, M.; Siddiqui, I.A.; Mukhtar, H. Cancer preventive and therapeutic effects of EGCG, the major polyphenol in green tea. Egypt. J. Basic Appl. Sci. 2018, 5, 1–23. [Google Scholar] [CrossRef] [Green Version]
- Braicu, C.; Gherman, C.D.; Irimie, A.; Berindan-Neagoe, I. Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells. J. Nanosci. Nanotechnol. 2013, 13, 632–637. [Google Scholar] [CrossRef] [PubMed]
- Magee, P.J.; Raschke, M.; Steiner, C.; Duffin, J.G.; Pool-Zobel, B.L.; Jokela, T.; Wahala, K.; Rowland, I.R. Equol: A comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro. Nutr. Cancer 2006, 54, 232–242. [Google Scholar] [CrossRef] [PubMed]
C ring | Saturated | |
Insaturated | ||
B ring |
Flavonoid Subclass | Name | Cancer Cells/Effects | Ref. |
---|---|---|---|
Flavanone | Naringenin (1) | hepatocellular carcinoma (IC50 = 100 µM) gastric cancer (IC50 = 10 µM) melanoma (IC50 = 3 µM) non-small-cell lung carcinoma (IC50 = 100 µM) | [35,165] |
Hesperetin (2) | gastric (IC50 = 40 μM) breast (IC50 = 20 μM) prostate (IC50 = 90 μM) colon (IC50 = 100 μM) lung (IC50 = 40 μM) liver (IC50 = 87 μM) | [39] | |
Alpinetin (4) | lung (IC50 = 25 μM) gastric (IC50 = 120 μM) ovarian (IC50 = 50 μM) pancreatic (IC50 = 60 μg/mL) | [40,41,42,166] | |
Persicogenin (5) | human cervical cancer (IC50 = 500 μg/mL) breast carcinoma (IC50 = 500 μg/mL) human colon cancer (IC50 = 500 μg/mL) | [44] | |
Homoeriodictyol (6) | human cervical cancer (IC50 = 500 μg/mL) breast carcinoma (IC50 = 500 μg/mL) human colon cancer (IC50 = 250 μg/mL) | [44] | |
Didymin (7) | neuroblastoma (IC50 = 50 μM) lung (IC50 = 11.06 μM) | [50,52,167] | |
Flavone | Vitexin (8) | leukemia (IC50 = 200 μM) glioblastoma (IC50 = 32 μM) hepatocellular carcinoma (IC50 = 5 μM) lung carcinoma (IC50 = 40 μM) | [53,168,169,170] |
Baicalin (9) | breast (IC50 = 100 μM) colon (IC50 = 20 μM) prostate (IC50 = 150 μM) lung (IC50 = 80 μg/mL) gastric (IC50 = 80 μM) osteosarcoma (IC50 = 25 μM) | [60,167,171,172,173,174] | |
Ficine (20) | CDK1 and CDK5 inhibition (IC50 = 0.04 µM) | [105] | |
(−)-O-demthylbuchenavianine (21) | CDK1 inhibition (IC50 = 0.03 µM) CDK5 inhibition (IC50 = 0.05 µM) | [105] | |
R-Leucoflavonine (23) | hepatocellular carcinoma (IC50 = 52.9 µM) | [103] | |
Flavopiridol (29) | CDK1 inhibition (IC50 = 30 nM) CDK7 inhibition (IC50 = 10 nM) CDK9 inhibition (IC50 = 3 nM) colon-carcinoma (IC50 = 20 nM) breast cancer (IC50 = 75 nM) gastric adenocarcinoma (111 nM) | [175,176,177] | |
Riviciclib (30) | CDK1 inhibition (IC50 = 79 nM) CDK9 inhibition (IC50 = 20 nM) | [177] | |
32 | gastric carcinoma (IC50 = 3.8 µM) | [131] | |
33 | breast (IC50 = 16.6 μM) | [134] | |
Flavone−dipeptide hybrid L-Val-OH (41) | leukemia (IC50 = 9.2 µM) | [117] | |
Flavonol | Taxifolin (14) | colorectal (IC50 = 40 µM) breast (IC50 = 10 µM) lung (IC50 = 25 µM) skin (IC50 = 80 µM) | [178] |
Quercetin−glutamic acid conjugate 7-O-Glu-Q (35) | MDR uterine sarcoma (IC50 = 0.14 μM) | [141] | |
L-valinequercetin diorganotin(IV) (38) | cervix (GI50 < 10 μg/mL) breast (GI50 < 10 μg/mL) liver (GI50 < 10 μg/mL) pancreatic (GI50 < 10 μg/mL) | [140] | |
Flavanol | (−)-epigallocatechin-3-gallate (EGCG) (10) | prostatic adenocarcinoma (IC50 = 39 µM) colon (IC50 = 3 µM) adrenal (IC50 = 20 µM) breast (IC50 = 20 µM) melanoma (IC50 = 7 µM) pancreatic (IC50 < 50 µM) | [179,180,181,182] |
Daphnegiralin A4 (24) | hepatocellular carcinoma (IC50 = 5.1 µM) | [107] | |
Daphnegiralins B1: (2-S,2′-R) (25) Daphnegiralins B2: (2-R,2′-S) (26) | hepatocellular carcinoma (IC50 = 6.1 µM) | [107] | |
Daphnegiralins B3: (2-S,2′-S) (27) Daphnegiralins B4: (2-R,2′-R) (28) | hepatocellular carcinoma (IC50 = 5.4 µM) | [107] | |
Isoflavone | S-(−)-equol (18) | breast cancer (IC50 = 10 µM) prostate cancer (IC50 = 5 µM) | [97,183] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Pinto, C.; Cidade, H.; Pinto, M.; Tiritan, M.E. Chiral Flavonoids as Antitumor Agents. Pharmaceuticals 2021, 14, 1267. https://doi.org/10.3390/ph14121267
Pinto C, Cidade H, Pinto M, Tiritan ME. Chiral Flavonoids as Antitumor Agents. Pharmaceuticals. 2021; 14(12):1267. https://doi.org/10.3390/ph14121267
Chicago/Turabian StylePinto, Cláudia, Honorina Cidade, Madalena Pinto, and Maria Elizabeth Tiritan. 2021. "Chiral Flavonoids as Antitumor Agents" Pharmaceuticals 14, no. 12: 1267. https://doi.org/10.3390/ph14121267
APA StylePinto, C., Cidade, H., Pinto, M., & Tiritan, M. E. (2021). Chiral Flavonoids as Antitumor Agents. Pharmaceuticals, 14(12), 1267. https://doi.org/10.3390/ph14121267