Synthesis, Biological Evaluation and Molecular Docking Study of Cyclic Diarylheptanoids as Potential Anticancer Therapeutics

Author(s): Yang Lu, Wencui Yin, Mohammad S. Alam, Adnan A. Kadi, Yurngdong Jahng, Youngjoo Kwon*, A.F.M. Motiur Rahman*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 4 , 2020


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Graphical Abstract:


Abstract:

Background: Cancer is one of the leading causes of mortality globally. To cope with cancer, it is necessary to develop anticancer drugs. Bioactive natural products, i.e. diarylheptanoids, have gained significant attention of researchers owing to their intriguing structures and potent biological activities. In this article, considering the development of anticancer drugs with enhanced selectivity towards cancerous cells, a series of Cyclic Diarylheptanoids (CDHs) are designed, synthesized and evaluated their biological activity.

Objective: To establish an easy route for the synthesis of diarylheptanoids, and evaluate their antiproliferative, and topoisomerase-I & -IIα inhibitory activities, for developing potential anticancer drugs among CDHs.

Methods: Diarylheptanoids were synthesized from reported linear diarylheptanoids using the classical Ullmann reaction. Antibacterial activity was evaluated by the filter paper disc diffusion method. Cell viability was assessed by measuring mitochondrial dehydrogenase activity with a Cell Counting Kit (CCK-8). Topoisomerases I and II (topo-I and -IIα) inhibitory activity was measured by the assessment of relaxation of supercoiled pBR322 plasmid DNA. IFD protocol of Schrodinger Maestro v11.1 was used to characterize the binding pattern of studied compounds with the ATPase domain of the human topo-IIα.

Results: The synthesized CDHs were evaluated for their biological activities (antibacterial, antiproliferative, and topoisomerase-I & -IIα inhibitory activities, respectively). Leading to obtain a series of anticancer agents with the least inhibitory activities against different microbes, improving their selectivity for cancer cells. In brief, most of the synthesized CDHs had excellent antiproliferative activity against T47D (human breast cancer cell line). Pterocarine possessed the strongest activity (2i; IC50 = 0.63µM) against T47D. The cyclic diarylheptanoid 2b induced 30% inhibition of topoisomerase-IIα activity at 100μM compared with the reference of etoposide, which induced 72% inhibition. Among the tested compounds, galeon (2h) displayed very low activity against four bacterial strains. Compounds 2b, 2h, and 2i formed hydrogen bonds with Thr215, Asn91, Asn120, Ala167, Lys168 and Ile141 residues, which are important for binding of ligand compound to the ATPase binding site of topoisomerase IIα by acting as ATP competitive molecule validated by docking study. In silico Absorption, Distribution, Metabolism and Excretion (ADME) analysis revealed the predicted ADME parameters of the studied compounds which showed recommended values.

Conclusion: A series of CDHs were synthesized and evaluated for their antibacterial, antiproliferative, and topo-I & -IIα inhibitory activities. SARs study, molecular docking study and in silico ADME analysis were conducted. Five compounds exhibited excellent and selective antiproliferative activity against the human breast cancer cell line (T47D). Among them, a compound 2h showed topo-IIα activity by 30% at 100µM, which represented a moderate intensity of inhibition compared with etoposide. Three of them formed hydrogen bonds with Thr215, Asn91, Asn120, and Ala167 residues, which are considered as crucial residues for binding to the ATPase domain of topoisomerase IIα. According to in silico drug-likeness property analysis, three compounds are expected to show superiority over etoposide in case of absorption, distribution, metabolism and excretion.

Keywords: Diarylheptanoids, cyclic diarylheptanoids, Topo-I, Topo-IIα, antiproliferative activity, topoisomerases inhibitor.

[1]
Block, K.I.; Gyllenhaal, C.; Lowe, L.; Amedei, A.; Amin, A.R.M.R.; Amin, A.; Aquilano, K.; Arbiser, J.; Arreola, A.; Arzumanyan, A.; Ashraf, S.S.; Azmi, A.S.; Benencia, F.; Bhakta, D.; Bilsland, A.; Bishayee, A.; Blain, S.W.; Block, P.B.; Boosani, C.S.; Carey, T.E.; Carnero, A.; Carotenuto, M.; Casey, S.C.; Chakrabarti, M.; Chaturvedi, R.; Chen, G.Z.; Chen, H.; Chen, S.; Chen, Y.C.; Choi, B.K.; Ciriolo, M.R.; Coley, H.M.; Collins, A.R.; Connell, M.; Crawford, S.; Curran, C.S.; Dabrosin, C.; Damia, G.; Dasgupta, S.; DeBerardinis, R.J.; Decker, W.K.; Dhawan, P.; Diehl, A.M.E.; Dong, J.T.; Dou, Q.P.; Drew, J.E.; Elkord, E.; El-Rayes, B.; Feitelson, M.A.; Felsher, D.W.; Ferguson, L.R.; Fimognari, C.; Firestone, G.L.; Frezza, C.; Fujii, H.; Fuster, M.M.; Generali, D.; Georgakilas, A.G.; Gieseler, F.; Gilbertson, M.; Green, M.F.; Grue, B.; Guha, G.; Halicka, D.; Helferich, W.G.; Heneberg, P.; Hentosh, P.; Hirschey, M.D.; Hofseth, L.J.; Holcombe, R.F.; Honoki, K.; Hsu, H.Y.; Huang, G.S.; Jensen, L.D.; Jiang, W.G.; Jones, L.W.; Karpowicz, P.A.; Keith, W.N.; Kerkar, S.P.; Khan, G.N.; Khatami, M.; Ko, Y.H.; Kucuk, O.; Kulathinal, R.J.; Kumar, N.B.; Kwon, B.S.; Le, A.; Lea, M.A.; Lee, H.Y.; Lichtor, T.; Lin, L.T.; Locasale, J.W.; Lokeshwar, B.L.; Longo, V.D.; Lyssiotis, C.A.; MacKenzie, K.L.; Malhotra, M.; Marino, M.; Martinez-Chantar, M.L.; Matheu, A.; Maxwell, C.; McDonnell, E.; Meeker, A.K.; Mehrmohamadi, M.; Mehta, K.; Michelotti, G.A.; Mohammad, R.M.; Mohammed, S.I.; Morre, D.J.; Muralidhar, V.; Muqbil, I.; Murphy, M.P.; Nagaraju, G.P.; Nahta, R.; Niccolai, E.; Nowsheen, S.; Panis, C.; Pantano, F.; Parslow, V.R.; Pawelec, G.; Pedersen, P.L.; Poore, B.; Poudyal, D.; Prakash, S.; Prince, M.; Raffaghello, L.; Rathmell, J.C.; Rathmell, W.K.; Ray, S.K.; Reichrath, J.; Rezazadeh, S.; Ribatti, D.; Ricciardiello, L.; Robey, R.B.; Rodier, F.; Rupasinghe, H.P.V.; Russo, G.L.; Ryan, E.P.; Samadi, A.K.; Sanchez-Garcia, I.; Sanders, A.J.; Santini, D.; Sarkar, M.; Sasada, T.; Saxena, N.K.; Shackelford, R.E.; Shantha Kumara, H.M.C.; Sharma, D.; Shin, D.M.; Sidransky, D.; Siegelin, M.D.; Signori, E.; Singh, N.; Sivanand, S.; Sliva, D.; Smythe, C.; Spagnuolo, C.; Stafforini, D.M.; Stagg, J.; Subbarayan, P.R.; Sundin, T.; Talib, W.H.; Thompson, S.K.; Tran, P.T.; Ungefroren, H.; Vander Heiden, M.G.; Venkateswaran, V.; Vinay, D.S.; Vlachostergios, P.J.; Wang, Z.; Wellen, K.E.; Whelan, R.L.; Yang, E.S.; Yang, H.; Yang, X.; Yaswen, P.; Yedjou, C.; Yin, X.; Zhu, J.; Zollo, M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol., 2015, 35(Suppl.), S276-S304.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007] [PMID: 26590477]
[2]
Tsai-Kun, Li. Liu, L.F. Tumor cell death induced by topoisomerase-targeting drugs. Annu. Rev. Pharmacol., 2001, 41, 53-77.
[http://dx.doi.org/10.1146/annurev.pharmtox.41.1.53]
[3]
Pommier, Y. DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. Chem. Rev., 2009, 109(7), 2894-2902.
[http://dx.doi.org/10.1021/cr900097c] [PMID: 19476377]
[4]
Roy, S.; Hagen, K.D.; Maheswari, P.U.; Lutz, M.; Spek, A.L.; Reedijk, J.; van Wezel, G.P. Phenanthroline derivatives with improved selectivity as DNA-targeting anticancer or antimicrobial drugs. ChemMedChem, 2008, 3(9), 1427-1434.
[http://dx.doi.org/10.1002/cmdc.200800097] [PMID: 18537202]
[5]
Keserü, G.M.; Nógrádi, M. The chemistry of natural diarylheptanoids. In: In Studies in Natural Products Chemistry, Elsevier, Ed.; Atta ur, R, 1995; 17, pp. 1687-1708.
[http://dx.doi.org/10.1016/S1572-5995(05)80090-0]
[6]
Lv, H.; She, G. Naturally occurring diarylheptanoids. Nat. Prod. Commun., 2010, 5(10), 1687-1708.
[http://dx.doi.org/10.1177/1934578X1000501035] [PMID: 21121274]
[7]
Zhu, J.; Islas-Gonzalez, G.; Bois-Choussy, M. Recent progress in isolation, bioactivity evaluation and total synthesis of diarylheptanoids. Org. Prep. Proced. Int., 2000, 32, 505-546.
[http://dx.doi.org/10.1080/00304940009355948]
[8]
Jahng, Y.; Park, J.G. Recent Studies on Cyclic 1,7-Diarylheptanoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis. Molecules, 2018, 23(12), 23.
[http://dx.doi.org/10.3390/molecules23123107] [PMID: 30486479]
[9]
Fu, G.; Zhang, W.; Du, D.; Ng, Y.P.; Ip, F.C.F.; Tong, R.; Ip, N.Y. Diarylheptanoids from Rhizomes of Alpinia officinarum Inhibit Aggregation of α-Synuclein. J. Agric. Food Chem., 2017, 65(31), 6608-6614.
[http://dx.doi.org/10.1021/acs.jafc.7b02021] [PMID: 28707886]
[10]
Velatooru, L.R.; Vakamullu, S.; Penugurti, V.; S, P.R. Alpinoid c analog inhibits angiogenesis and induces apoptosis in COLO205 cell line. Chem. Biol. Interact., 2019, 308, 1-10.
[http://dx.doi.org/10.1016/j.cbi.2019.05.009] [PMID: 31071337]
[11]
Wu, H-C.; Cheng, M-J.; Peng, C-F.; Yang, S-C.; Chang, H-S.; Lin, C-H.; Wang, C-J.; Chen, I-S. Secondary metabolites from the stems of Engelhardia roxburghiana and their antitubercular activities. Phytochemistry, 2012, 82, 118-127.
[http://dx.doi.org/10.1016/j.phytochem.2012.06.014] [PMID: 22818359]
[12]
Zhang, Y-X.; Xia, B.; Zhou, Y.; Ding, L-S.; Peng, S-L. Two new cyclic diarylheptanoids from the stems of Ostryopsis nobilis. Chin. Chem. Lett., 2013, 24, 512-514.
[http://dx.doi.org/10.1016/j.cclet.2013.03.035]
[13]
Chiba, K.; Ichizawa, H.; Kawai, S.; Nishida, T. α-Glucosidase inhibition activity by cyclic diarylheptanoids from Alnus sieboldiana. J. Wood Chem. Technol., 2013, 33, 44-51.
[http://dx.doi.org/10.1080/02773813.2012.723778]
[14]
Ibrahim, S.R.; Fouad, M.A.; Abdel-Lateff, A.; Okino, T.; Mohamed, G.A. Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica. Nat. Prod. Res., 2014, 28(20), 1765-1771.
[http://dx.doi.org/10.1080/14786419.2014.947489] [PMID: 25116915]
[15]
Ibrahim, S.R.M.; Mohamed, G.A.; Khedr, A.I.M.; Aljaeid, B.M. Alnuheptanoid B: a new cyclic diarylheptanoid from Alnus japonica stem bark. Rec. Nat. Prod., 2016, 10, 362-368.
[16]
Akihisa, T.; Takeda, A.; Akazawa, H.; Kikuchi, T.; Yokokawa, S.; Ukiya, M.; Fukatsu, M.; Watanabe, K. Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives. Chem. Biodivers., 2012, 9(8), 1475-1489.
[http://dx.doi.org/10.1002/cbdv.201200024] [PMID: 22899608]
[17]
Deguchi, J.; Motegi, Y.; Nakata, A.; Hosoya, T.; Morita, H. Cyclic diarylheptanoids as inhibitors of NO production from Acer nikoense. J. Nat. Med., 2013, 67(1), 234-239.
[http://dx.doi.org/10.1007/s11418-012-0660-0] [PMID: 22456895]
[18]
Akazawa, H.; Fujita, Y.; Banno, N.; Watanabe, K.; Kimura, Y.; Manosroi, A.; Manosroi, J.; Akihisa, T. Three new cyclic diarylheptanoids and other phenolic compounds from the bark of Myrica rubra and their melanogenesis inhibitory and radical scavenging activities. J. Oleo Sci., 2010, 59(4), 213-221.
[http://dx.doi.org/10.5650/jos.59.213] [PMID: 20299768]
[19]
Li, J.; Sun, J-X.; Yu, H-Y.; Chen, Z-Y.; Zhao, X-Y.; Ruan, H-L. Diarylheptanoids from the root bark of Juglans cathayensis. Chin. Chem. Lett., 2013, 24, 521-523.
[http://dx.doi.org/10.1016/j.cclet.2013.03.050]
[20]
Lin, Y.; Peng, X.; Ruan, H. Diarylheptanoids from the fresh pericarps of Juglans hopeiensis. Fitoterapia, 2019, 136, 004.
[http://dx.doi.org/10.1016/j.fitote.2019.05.004]
[21]
Kikuzaki, H.; Nakatani, N. Cyclic diarylheptanoids from rhizomes of Zingiber officinale. Phytochemistry, 1996, 43, 273-277.
[http://dx.doi.org/10.1016/0031-9422(96)00214-2]
[22]
Costantino, V.; Fattorusso, E.; Mangoni, A.; Perinu, C.; Teta, R.; Panza, E.; Ianaro, A. Tedarenes A and B: structural and stereochemical analysis of two new strained cyclic diarylheptanoids from the marine sponge Tedania ignis. J. Org. Chem., 2012, 77(15), 6377-6383.
[http://dx.doi.org/10.1021/jo300295j] [PMID: 22443364]
[23]
Masullo, M.; Mari, A.; Cerulli, A.; Bottone, A.; Kontek, B.; Olas, B.; Pizza, C.; Piacente, S. Quali-quantitative analysis of the phenolic fraction of the flowers of Corylus avellana, source of the Italian PGI product “Nocciola di Giffoni”: Isolation of antioxidant diarylheptanoids. Phytochemistry, 2016, 130, 273-281.
[http://dx.doi.org/10.1016/j.phytochem.2016.06.007] [PMID: 27372151]
[24]
Li, C.; Liu, J.X.; Zhao, L.; Di, D.L.; Meng, M.; Jiang, S.X. Capillary zone electrophoresis for separation and analysis of four diarylheptanoids and an alpha-tetralone derivative in the green walnut husks (Juglans regia L.). J. Pharm. Biomed. Anal., 2008, 48(3), 749-753.
[http://dx.doi.org/10.1016/j.jpba.2008.07.016] [PMID: 18771874]
[25]
Liu, J.X.; Di, D.L.; Huang, X.Y.; Li, C. Two new diarylheptanoids from the pericarps of Juglans regia L. Chin. Chem. Lett., 2007, 18, 943-946.
[http://dx.doi.org/10.1016/j.cclet.2007.05.028]
[26]
Liu, H.B.; Cui, C.B.; Cai, B.; Gu, Q.Q.; Zhang, D.Y.; Zhao, Q.C.; Guan, H.S. Pterocarine, a new diarylheptanoid from Pterocarya tonkinesis, its cell cycle inhibition at G0/G1 phase and induction of apoptosis in HCT-15 and K562 cells. Chin. Chem. Lett., 2005, 16, 215-218.
[27]
Kontiza, I.; Stavri, M.; Zloh, M.; Vagias, C.; Gibbons, S.; Roussis, V. New metabolites with antibacterial activity from the marine angiosperm Cymodocea nodosa. Tetrahedron, 2008, 64, 1696-1702.
[http://dx.doi.org/10.1016/j.tet.2007.12.007]
[28]
Gonzalez, G.I.; Zhu, J. First total synthesis of acerogenin c and aceroside IV. J. Org. Chem., 1997, 62, 7544-7545.
[http://dx.doi.org/10.1021/jo9714324]
[29]
Gonzalez, G.I.; Zhu, J. A Unified Strategy toward the Synthesis of Acerogenin-Type Macrocycles: Total Syntheses of Acerogenins A, B, C, and L and Aceroside IV. J. Org. Chem., 1999, 64(3), 914-924.
[http://dx.doi.org/10.1021/jo981844s] [PMID: 11674163]
[30]
Jeong, B-S.; Wang, Q.; Son, J-K.; Jahng, Y. A Versatile synthesis of cyclic diphenyl ether-type diarylheptanoids: Acerogenins, (±)-galeon, and (±)-pterocarine. Eur. J. Org. Chem., 2007, 2007, 1338-1344.
[http://dx.doi.org/10.1002/ejoc.200600938]
[31]
Keserü, G.M.; Nógrádi, M.; Szöllösy, Á. Synthesis of acerogenin A and (+)-acerogenin a, two macrocyclic diarylheptanoid constituents of Acer nikoense. Eur. J. Org. Chem., 1998, 1998, 521-524.
[http://dx.doi.org/10.1002/(SICI)1099-0690(199803)1998:3<521:AID-EJOC521>3.0.CO;2-I]
[32]
Pitsinos, E.N.; Vidali, V.P.; Couladouros, E.A. Diaryl ether formation in the synthesis of natural products. Eur. J. Org. Chem., 2011, 2011, 1207-1222.
[http://dx.doi.org/10.1002/ejoc.201001520]
[33]
Semmelhack, M.F.; Helquist, P.; Jones, L.D.; Keller, L.; Mendelson, L.; Ryono, L.S.; Gorzynski Smith, J.; Stauffer, R.D. Reaction of aryl and vinyl halides with zerovalent nickel - preparative aspects and the synthesis of alnusone. J. Am. Chem. Soc., 1981, 103, 6460-6471.
[http://dx.doi.org/10.1021/ja00411a034]
[34]
Wang, Q.; Son, J.K.; Jahng, Y. First total synthesis of cytotoxic diarylheptanoids, galeon, and pterocarine. Synth. Commun., 2007, 37, 675-681.
[http://dx.doi.org/10.1080/00397910601131015]
[35]
Whiting, D.A.; Wood, A.F. Cyclisation of 1,7-diarylheptanoids through oxidative, reductive, and photochemical radical processes: Total syntheses of the m,m-bridged biaryls myricanone and (±)-myricanol, and a related diaryl ether. Tetrahedron Lett., 1978, 19, 2335-2338.
[http://dx.doi.org/10.1016/S0040-4039(01)91529-1]
[36]
Semmelhack, M.F.; Ryono, L.S. Nickel-promoted synthesis of cyclic biphenyls. Total synthesis of alnusone dimethyl ether. J. Am. Chem. Soc., 1975, 97
[http://dx.doi.org/10.1021/ja00846a084]
[37]
Ishida, J.; Kozuka, M.; Tokuda, H.; Nishino, H.; Nagumo, S.; Lee, K-H.; Nagai, M. Chemopreventive potential of cyclic diarylheptanoids. Bioorg. Med. Chem., 2002, 10(10), 3361-3365.
[http://dx.doi.org/10.1016/S0968-0896(02)00164-5] [PMID: 12150883]
[38]
Akazawa, H.; Akihisa, T.; Taguchi, Y.; Banno, N.; Yoneima, R.; Yasukawa, K. Melanogenesis inhibitory and free radical scavenging activities of diarylheptanoids and other phenolic compounds from the bark of Acer nikoense. Biol. Pharm. Bull., 2006, 29(9), 1970-1972.
[http://dx.doi.org/10.1248/bpb.29.1970] [PMID: 16946520]
[39]
Dai, G.; Tong, Y.; Chen, X.; Ren, Z.; Yang, F. In vitro anticancer activity of myricanone in human lung adenocarcinoma A549 cells. Chemotherapy, 2014, 60(2), 81-87.
[http://dx.doi.org/10.1159/000371738] [PMID: 25720464]
[40]
Akihisa, T.; Taguchi, Y.; Yasukawa, K.; Tokuda, H.; Akazawa, H.; Suzuki, T.; Kimura, Y. Acerogenin M, a cyclic diarylheptanoid, and other phenolic compounds from Acer nikoense and their anti-inflammatory and anti-tumor-promoting effects. Chem. Pharm. Bull. (Tokyo), 2006, 54(5), 735-739.
[http://dx.doi.org/10.1248/cpb.54.735] [PMID: 16651781]
[41]
Ishida, J.; Kozuka, M.; Wang, H.; Konoshima, T.; Tokuda, H.; Okuda, M.; Yang Mou, X.; Nishino, H.; Sakurai, N.; Lee, K.H.; Nagai, M. Antitumor-promoting effects of cyclic diarylheptanoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis. Cancer Lett., 2000, 159(2), 135-140.
[http://dx.doi.org/10.1016/S0304-3835(00)00538-3] [PMID: 10996724]
[42]
Lin, W-Y.; Peng, C-F.; Tsai, I-L.; Chen, J-J.; Cheng, M-J.; Chen, I-S. Antitubercular constituents from the roots of Engelhardia roxburghiana. Planta Med., 2005, 71(2), 171-175.
[http://dx.doi.org/10.1055/s-2005-837786] [PMID: 15729627]
[43]
Takahashi, M.; Fuchino, H.; Sekita, S.; Satake, M. In vitro leishmanicidal activity of some scarce natural products. Phytother. Res., 2004, 18(7), 573-578.
[http://dx.doi.org/10.1002/ptr.1502] [PMID: 15305319]
[44]
Yonezawa, T.; Lee, J-W.; Akazawa, H.; Inagaki, M.; Cha, B-Y.; Nagai, K.; Yagasaki, K.; Akihisa, T.; Woo, J-T. Osteogenic activity of diphenyl ether-type cyclic diarylheptanoids derived from Acer nikoense. Bioorg. Med. Chem. Lett., 2011, 21(11), 3248-3251.
[http://dx.doi.org/10.1016/j.bmcl.2011.04.041] [PMID: 21550801]
[45]
Morikawa, T.; Tao, J.; Toguchida, I.; Matsuda, H.; Yoshikawa, M. Structures of new cyclic diarylheptanoids and inhibitors of nitric oxide production from Japanese folk medicine Acer nikoense. J. Nat. Prod., 2003, 66(1), 86-91.
[http://dx.doi.org/10.1021/np020351m] [PMID: 12542351]
[46]
Tao, J.; Morikawa, T.; Toguchida, I.; Ando, S.; Matsuda, H.; Yoshikawa, M. Inhibitors of nitric oxide production from the bark of Myrica rubra: structures of new biphenyl type diarylheptanoid glycosides and taraxerane type triterpene. Bioorg. Med. Chem., 2002, 10(12), 4005-4012.
[http://dx.doi.org/10.1016/S0968-0896(02)00314-0] [PMID: 12413852]
[47]
Wang, J.; Dong, S.; Wang, Y.; Lu, Q.; Zhong, H.; Du, G.; Zhang, L.; Cheng, Y. Cyclic diarylheptanoids from Myrica nana inhibiting nitric oxide release. Bioorg. Med. Chem., 2008, 16(18), 8510-8515.
[http://dx.doi.org/10.1016/j.bmc.2008.08.020] [PMID: 18723353]
[48]
Kang, H-M.; Ryong Kim, J.; Jeong, T-S.; Choi, S-G.; Ryu, Y-H.; Taeg Oh, G.; Baek, N-I.; Kwon, B-M. Cyclic diarylheptanoids inhibit cell-mediated low-density lipoprotein oxidation. Nat. Prod. Res., 2006, 20(2), 139-143.
[http://dx.doi.org/10.1080/14786410500045895] [PMID: 16319007]
[49]
Matsuda, H.; Yamazaki, M.; Matsuo, K.; Asanuma, Y.; Kubo, M. Anti-androgenic activity of Myricae Cortex--isolation of active constituents from bark of Myrica rubra. Biol. Pharm. Bull., 2001, 24(3), 259-263.
[http://dx.doi.org/10.1248/bpb.24.259] [PMID: 11256481]
[50]
Morita, H.; Deguchi, J.; Motegi, Y.; Sato, S.; Aoyama, C.; Takeo, J.; Shiro, M.; Hirasawa, Y. Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense. Bioorg. Med. Chem. Lett., 2010, 20(3), 1070-1074.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.036] [PMID: 20036535]
[51]
Li, G.; Lee, S-Y.; Lee, K-S.; Lee, S-W.; Kim, S-H.; Lee, S-H.; Lee, C-S.; Woo, M-H.; Son, J-K. DNA topoisomerases I and II inhibitory activity of constituents isolated from Juglans mandshurica. Arch. Pharm. Res., 2003, 26(6), 466-470.
[http://dx.doi.org/10.1007/BF02976864] [PMID: 12877556]
[52]
Ahmad, P.; Woo, H.; Jun, K-Y.; Kadi, A.A.; Abdel-Aziz, H.A.; Kwon, Y.; Rahman, A.F. Design, synthesis, topoisomerase I & II inhibitory activity, antiproliferative activity, and structure-activity relationship study of pyrazoline derivatives: An ATP-competitive human topoisomerase IIα catalytic inhibitor. Bioorg. Med. Chem., 2016, 24(8), 1898-1908.
[http://dx.doi.org/10.1016/j.bmc.2016.03.017] [PMID: 26988802]
[53]
Islam, M.S.; Park, S.; Song, C.; Kadi, A.A.; Kwon, Y.; Rahman, A.F. Fluorescein hydrazones: A series of novel non-intercalative topoisomerase IIα catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells. Eur. J. Med. Chem., 2017, 125, 49-67.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.004] [PMID: 27654394]
[54]
Rahman, A.F.M.M.; Park, S-E.; Kadi, A.A.; Kwon, Y. Fluorescein hydrazones as novel nonintercalative topoisomerase catalytic inhibitors with low DNA toxicity. J. Med. Chem., 2014, 57(21), 9139-9151.
[http://dx.doi.org/10.1021/jm501263m] [PMID: 25333701]
[55]
Lee, K-S.; Li, G.; Kim, S.H.; Lee, C-S.; Woo, M-H.; Lee, S-H.; Jhang, Y-D.; Son, J-K. Cytotoxic diarylheptanoids from the roots of Juglans mandshurica. J. Nat. Prod., 2002, 65(11), 1707-1708.
[http://dx.doi.org/10.1021/np0201063] [PMID: 12444709]
[56]
Motiur Rahman, A.F.M.; Lu, Y.; Lee, H.J.; Jo, H.; Yin, W.; Alam, M.S.; Cha, H.; Kadi, A.A.; Kwon, Y.; Jahng, Y. Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure-activity relationship studies. Arch. Pharm. Res., 2018, 41(12), 1131-1148.
[http://dx.doi.org/10.1007/s12272-018-1004-8] [PMID: 29397550]
[57]
Park, S.H.; Park, S.J.; Kim, J-O.; Shin, J.H.; Kim, E.S.; Jo, Y.K.; Kim, J-S.; Park, S.J.; Jin, D.H.; Hwang, J.J.; Lee, S.J.; Jeong, S.Y.; Lee, C.; Kim, I.; Cho, D.H. Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis. Biomol. Ther. (Seoul), 2013, 21(1), 29-34.
[http://dx.doi.org/10.4062/biomolther.2012.088] [PMID: 24009855]
[58]
Jun, K.Y.; Kwon, H.; Park, S.E.; Lee, E.; Karki, R.; Thapa, P.; Lee, J.H.; Lee, E.S.; Kwon, Y. Discovery of dihydroxylated 2,4-diphenyl-6-thiophen-2-yl-pyridine as a non-intercalative DNA-binding topoisomerase II-specific catalytic inhibitor. Eur. J. Med. Chem., 2014, 80, 428-438.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.066] [PMID: 24796883]
[59]
Park, S.E.; Chang, I.H.; Jun, K.Y.; Lee, E.; Lee, E.S.; Na, Y.; Kwon, Y. 3-(3-Butylamino-2-hydroxy-propoxy)-1-hydroxy-xanthen-9-one acts as a topoisomerase IIα catalytic inhibitor with low DNA damage. Eur. J. Med. Chem., 2013, 69, 139-145.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.048] [PMID: 24013413]
[60]
Zhong, H.; Tran, L.M.; Stang, J.L. Induced-fit docking studies of the active and inactive states of protein tyrosine kinases. J. Mol. Graph. Model., 2009, 28(4), 336-346.
[http://dx.doi.org/10.1016/j.jmgm.2009.08.012] [PMID: 19767223]
[61]
Carlson, H.A. Protein flexibility and drug design: how to hit a moving target. Curr. Opin. Chem. Biol., 2002, 6(4), 447-452.
[http://dx.doi.org/10.1016/S1367-5931(02)00341-1] [PMID: 12133719]
[62]
Arifuzzaman, M.; Mitra, S.; Jahan, S.I.; Jakaria, M.; Abeda, T.; Absar, N.; Dash, R. A Computational workflow for the identification of the potent inhibitor of type II secretion system traffic ATPase of Pseudomonas aeruginosa. Comput. Biol. Chem., 2018, 76, 191-201.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.07.012] [PMID: 30053700]
[63]
Release, S. 2: LigPrep, Schrödinger, LLC; New York, NY, 2017. 2017
[64]
Wizard, P.P. Epik version 2.2, Impact version 5.7, Prime version 3; Schrödinger, LLC: New York, NY, 2011.
[65]
Wei, H.; Ruthenburg, A.J.; Bechis, S.K.; Verdine, G.L. Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J. Biol. Chem., 2005, 280(44), 37041-37047.
[http://dx.doi.org/10.1074/jbc.M506520200] [PMID: 16100112]
[66]
Rostkowski, M.; Olsson, M.H.; Søndergaard, C.R.; Jensen, J.H. Graphical analysis of pH-dependent properties of proteins predicted using PROPKA. BMC Struct. Biol., 2011, 11, 6.
[http://dx.doi.org/10.1186/1472-6807-11-6] [PMID: 21269479]
[67]
Press, S. QikProp 3.4 user manual LLC.. New York, NY, 2011.
[68]
Calame, W.; van der Waals, R.; Douwes-Idema, N.; Mattie, H.; van Furth, R. Antibacterial effect of etoposide in vitro. Antimicrob. Agents Chemother., 1988, 32(9), 1456-1457.
[http://dx.doi.org/10.1128/AAC.32.9.1456] [PMID: 3196009]
[69]
Ramesh, K.; Gundampati, R.K.; Singh, S.; Mitra, K.; Shukla, A.; Jagannadham, M.V.; Chattopadhyay, D.; Misra, N.; Ray, B. Self-assembly, doxorubicin-loading and antibacterial activity of well-defined ABA-type amphiphilic poly(N-vinylpyrrolidone)-b-poly(d,l-lactide)-b-poly(N-vinyl pyrrolidone) triblock copolymers. RSC Advances, 2016, 6, 25864-25876.
[http://dx.doi.org/10.1039/C5RA23239B]
[70]
Dong, Q.; Luo, J.; Qiu, W.; Cai, L.; Anjum, S.I.; Li, B.; Hou, M.; Xie, G.; Sun, G. Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2. Molecules, 2016, 21(8), 978.
[http://dx.doi.org/10.3390/molecules21080978] [PMID: 27472315]
[71]
Nitiss, J.L. Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer, 2009, 9(5), 338-350.
[http://dx.doi.org/10.1038/nrc2607] [PMID: 19377506]
[72]
Ekins, S.; Waller, C.L.; Swaan, P.W.; Cruciani, G.; Wrighton, S.A.; Wikel, J.H. Progress in predicting human ADME parameters in silico. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 251-272.
[http://dx.doi.org/10.1016/S1056-8719(00)00109-X] [PMID: 11274894]
[73]
Ghose, A.K.; Viswanadhan, V.N.; Wendoloski, J.J. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J. Comb. Chem., 1999, 1(1), 55-68.
[http://dx.doi.org/10.1021/cc9800071] [PMID: 10746014]
[74]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[75]
Clark, D.E. In silico prediction of blood-brain barrier permeation. Drug Discov. Today, 2003, 8(20), 927-933.
[http://dx.doi.org/10.1016/S1359-6446(03)02827-7] [PMID: 14554156]
[76]
Lionta, E.; Spyrou, G.; Vassilatis, D.K.; Cournia, Z. Structure-based virtual screening for drug discovery: principles, applications and recent advances. Curr. Top. Med. Chem., 2014, 14(16), 1923-1938.
[http://dx.doi.org/10.2174/1568026614666140929124445] [PMID: 25262799]
[77]
Ajay; Bemis, G.W.; Murcko, M.A. Designing libraries with CNS activity. J. Med. Chem., 1999, 42, 4942-4951.
[http://dx.doi.org/10.1021/jm990017w]
[78]
Crivori, P.; Cruciani, G.; Carrupt, P-A.; Testa, B. Predicting blood-brain barrier permeation from three-dimensional molecular structure. J. Med. Chem., 2000, 43(11), 2204-2216.
[http://dx.doi.org/10.1021/jm990968+] [PMID: 10841799]
[79]
Doniger, S.; Hofmann, T.; Yeh, J. Predicting CNS permeability of drug molecules: comparison of neural network and support vector machine algorithms. J. Comput. Biol., 2002, 9(6), 849-864.
[http://dx.doi.org/10.1089/10665270260518317] [PMID: 12614551]
[80]
Keserû, G.M.; Molnár, L.; Greiner, I. A neural network based virtual high throughput screening test for the prediction of CNS activity. Comb. Chem. High Throughput Screen., 2000, 3(6), 535-540.
[http://dx.doi.org/10.2174/1386207003331346] [PMID: 11121522]
[81]
Chemi, G.; Gemma, S.; Campiani, G.; Brogi, S.; Butini, S.; Brindisi, M. Computational tool for fast in silico evaluation of hERG K+ channel affinity. Front Chem., 2017, 5, 7.
[http://dx.doi.org/10.3389/fchem.2017.00007] [PMID: 28503546]
[82]
Jorgensen, W.L.; Duffy, E.M. Prediction of drug solubility from structure. Adv. Drug Deliv. Rev., 2002, 54(3), 355-366.
[http://dx.doi.org/10.1016/S0169-409X(02)00008-X] [PMID: 11922952]


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VOLUME: 20
ISSUE: 4
Year: 2020
Published on: 14 May, 2020
Page: [464 - 475]
Pages: 12
DOI: 10.2174/1871520619666191125130237
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