[1]
Brown, D.; Superti, F.G. Rediscovering the sweet spot in drug discovery. Drug Discov. Today, 2003, 8, 1067-1077.
[2]
Overington, J.P.; Al-Lazikani, B.; Hopkins, A.L. How many drug targets are there? Nat. Rev. Drug Discov., 2006, 5, 993-996.
[3]
Szuromi, P.; Vinson, V.; Marshal, E. Rethinking drug discovery Science. Drug Discov. Today, 2004, 303, 1795.
[4]
Hartman, J.L.T.; Garvik, B.; Hartwell, L. Inciples for the buffering of genetic variation. Science, 2001, 291, 1001-1004.
[6]
Chen, S.; Chan, N.; Hsieh, T. New mechanistic and functional insights into DNA topoisomerases. Annu. Rev. Biochem., 2013, 82, 139-170.
[7]
Stringer, A.M.; Gibson, R.; Bowen, J.M.; Keefe, D. Chemotherapy-induced modifications to gastrointestinal microflora, evidence and implications of change. Curr. Drug Metab., 2009, 10, 79-83.
[8]
Stringer, A.; Gibson, R.; Logan, R.; Bowen, J.; Yeoh, A.; Laurence, J.; Keefe, D. Irinotecan-induced mucositis is associated with changes in intestinal mucins. Cancer Chemother. Pharmacol., 2009, 64, 123-132.
[9]
Lee, C.S.; Ryan, E.J.; Doherty, A.G. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer, the role of inflammation. World J. Gastroenterol., 2014, 20, 3751-3761.
[10]
Stein, A.; Voigt, W.; Jordan, K. Chemotherapy induced diarrhea, pathophysiology, frequency and guideline-based management. Ther. Adv. Med. Oncol., 2010, 2, 51-63.
[11]
Kwon, Y. Mechanism-based management for mucositis, option for treating side effects without compromising the efficacy of cancer therapy. OncoTargets Ther., 2016, 9, 2007-2016.
[12]
Fadeyi, O.O.; Adamson, S.T.; Myles, E.L.; Okoro, C.O. Novel fluorinated acridone derivatives, synthesis and evaluation as potential anticancer agents. Bioorg. Med. Chem. Lett., 2008, 18, 4172-4186.
[13]
Hidenori, N.; Young, B.K.; Hiroshi, T.; Minoru, Y.; Sueharu, H. FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp. Cell Res., 1998, 241, 126-133.
[14]
Ken, S.; Tadashi, K.; Hideki, S.; Akifumi, O.; Ohgi, T.; Chikashi, I. Romidepsin (FK228) and its analogs directly inhibit phosphatidylinositol 3-kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3-kinase dual inhibitors. Cancer Sci., 2012, 103, 1994-2001.
[15]
Odaa, A.B.C.; Ken, S.; Chikashi, I.; Koichi, N.; Tadashi, K.; Yurie, W.; Shuichi, F.; Ohgi, T. Predicting the structures of complexes between phosphoinositide3-kinase (PI3K) and romidepsin-related compounds for the drug design of PI3K/histone deacetylase dual inhibitors using computational docking and the ligand-based drug design approach. J. Mol. Graph. Model., 2014, 54, 46-53.
[16]
Ken, S.; Jin, I.; Koichi, N.; Akifumi, O.; Hideki, S.; Tadashi, K.; Chikashi, I. Biochemical, biological and structural properties of romidepsin (FK228) and its analogs as novel HDAC⁄PI3K dual inhibitors. Cancer Sci., 2015, 106, 208-215.
[17]
Ken, S.; Hiroo, I.; Sonoko, C.; Koichi, N.; Tadashi, K.; Chikashi, I. Antitumor activity and pharmacologic characterization of the depsipeptide analog as a novel histone deacetylase/ phosphatidylinositol 3-kinase dual inhibitor. Cancer Sci., 2017, 108, 1469-1475.
[18]
Stratikopoulos, E.E.; Dendy, M.; Szabolcs, M.; Khaykin, A.J.; Lefebvre, C.; Zhou, M.M.; Parsons, R. Kinase and BET inhibitors together clamp inhibition of PI3K signaling and overcome resistance to therapy. Cancer Cell, 2015, 27, 837-851.
[19]
Guan, Z.; Xu, B.; DeSilvio, M.L.; Shen, Z.; Arpornwirat, W.; Tong, Z.; Lorvidhaya, V.; Jiang, Z.; Yang, J.; Makhson, A.; Leung, W.L.; Russo, M.W.; Newstat, B.; Wang, L.; Chen, G.; Oliva, C.; Gomez, H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. Invest. New Drugs, 2013, 31, 734-741.
[20]
Mokhtari, R.B.; Homayouni, T.S.; Baluch, N.; Morgatskaya, E.; Kumar, S.; Das, B.; Yeger, H. Combination therapy in combating cancer. Oncotarget, 2017, 8, 38022-38043.
[21]
Mondello, P.; Derenzini, E.; Asgari, Z.; Philip, J.; Brea, E.J.; Seshan, V.; Hendrickson, R.C.; Stanchina, E.D.; Scheinberg, D.A.; Younes, A. Dual inhibition of histone deacetylases and phosphoinositide 3-kinase enhances therapeutic activity against B cell lymphoma. Oncotarget, 2017, 8, 14017-14028.
[22]
Andrews, F.H.; Singh, A.H.; Joshi, S.; Smith, C.A.; Morales, G.A.; Garlich, J.R.D.; Durden, D.L.; Kutateladze, T.G. Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis. Proc. Natl. Acad. Sci. USA, 2017, 114, 1072-1080.
[23]
Mendel, D.B.; Laird, A.D.; Xin, X.; Louie, S.G.; Christensen, J.G.; Li, G.; Schreck, R.E.; Abrams, T.J.; Ngai, T.J.; Lee, L.B.; Murray, L.J.; Carver, J.; Chan, E.; Moss, K.G.J.; Haznedar, J.O.; Sukbuntherng, S.; Blake, R.A.; Sun, L.; Tang, C.; Miller, T.; Shirazian, S.; McMahon, G.; Cherrington, J.M. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors, determination of apharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res., 2003, 9, 327-337.
[24]
Mitsui, H.; Takuwa, N.; Maruyama, T.; Maekawa, H.; Hirayama, H.; Sawatari, T.; Hashimoto, N.; Takuwa, Y.; Kimura, S. The MEK1-ERK map kinase pathway and the PI 3-kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver cancer cells. Int. J. Cancer, 2001, 92, 55-62.
[25]
Druker, B.J.; Lydon, N.B. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest., 2000, 105, 3-7.
[26]
Lai, C.J.; Bao, R.; Tao, X.; Wang, J.; Atoyan, R.; Qu, H.; Wang, D.G.; Yin, L.; Samson, M.; Forrester, J.; Zifcak, B.; Xu, G.S.; DellaRocca, S.; Zhai, H.X.; Cai, X.; Munger, W.E.; Keegan, M.; Pepicelli, C.V.; Qian, C. CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity. Cancer Res., 2010, 70, 3647-3656.
[27]
Shimizu, T.; LoRusso, P.M.; Papadopoulos, K.P.; Patnaik, A.; Beeram, M.; Smith, L.S.; Rasco, D.W.; Mays, T.A.; Chambers, G.; Ma, A.; Wang, J.; Laliberte, R.; Voi, M.A.; Tolcher, A.W. Phase I first-inhuman study of CUDC-101, a multitargeted inhibitor of HDACs, EGFR, and HER2 in patients with advanced solid tumors. Clin. Cancer Res., 2014, 20, 5032-5040.
[28]
Wang, J.; Pursell, N.W.; Samson, M.E.; Atoyan, R.; Ma, A.W.; Selmi, A.; Xu, W.; Cai, X.; Voi, M.; Savagner, P.; Lai, C.J. Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion. Mol. Cancer Ther., 2013, 12, 925-936.
[29]
Seo, S.Y. Multi-targeted hybrids based on HDAC inhibitors for anti-cancer drug discovery. Arch. Pharm. Res., 2012, 35, 197-200.
[30]
Cai, X.; Zhai, H.X.; Wang, J.; Forrester, J.; Qu, H.; Yin, L.; Lai, C.J.; Bao, R.; Qian, C. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J. Med. Chem., 2010, 53, 2000-2009.
[31]
Qian, C.; Lai, C.J.; Bao, R.; Wang, D.G.; Wang, J.; Xu, G.X.; Atoyan, R.; Qu, H.; Yin, L.; Samson, M.; Zifcak, B.; Ma, A.W.; DellaRocca, S.; Borek, M.; Zhai, H.X.; Cai, X.; Voi, M. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin. Cancer Res., 2012, 18, 4104-4113.
[32]
Kyu, Y.J.; Youngjoo, K. Proposal of dual inhibitor targeting ATPase domains of Topoisomerase II and heat shock protein 90. Biomol. Ther. , 2016, 24, 453-468.
[33]
Yingxiu, L.; Donghee, S.; So, H.K. Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J., 2013, 280, 775-793.
[34]
Bertos, N.R.; Gilquin, B.; Chan, G.K.; Yen, T.J.; Khochbin, S.; Yang, X.J. Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J. Biol. Chem., 2014, 279, 48246-48254.
[35]
Ruijter, A.J.; Gennip, A.H.; Caron, H.N.; Kemp, S.; Kuilenburg, A.B.P. Histone deacetylases (HDACs) characterization of the classical HDAC family. Biochem. J., 2003, 370, 737-749.
[36]
Jeremy, M.J.K.; Longlong, W.; Makoto, S.; Daniel, H.; Xiaoning, W.; Bruce, J.M.; Paul, H.; Heinz, G.; Patrick, M. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat. Chem. Biol., 2016, 12, 748-754.
[37]
Honore, S.; Pasquier, E.; Braguer, D. Understanding microtubule dynamics for improved cancer therapy. Cell. Mol. Life. Sci., 2005, 62, 3039-3056; b) Pellegrini, F.; Budman, D.R. Review: Tubulin function, action of antitubulin drugs, and new drug development. Cancer. Invest., 2005, 23, 264-273; c) Nepali, K.; Ojha, R.; Sharma, S.; Bedi, P.M.S.; Dhar, K.L. Tubulin inhibitors: A patent survey. Recent. Pat. Anti-Cancer Drug Discov., 2014, 9, 176-220.
[38]
Mehndiratta, S.; Sharma, S.; Kumar, S.; Nepali, K.; Rahman, A.; Zaman, K. Patents E Book Series; Bentham Science Publishers Ltd., 2015.
[39]
Xuan, Z.; Jie, Z.; Linjiang, T.; Yu, L.; Mingbo, S.; Yi, Z.; Jia, L.; Wei, L.; Yi, C. The discovery of colchicine-SAHA hybrids as a new class of antitumor Agents. Bioorg. Med. Chem., 2013, 21, 3240-3244.
[40]
Xuan, Z.; Yannan, K.; Jie, Z.; Mingbo, S.; Yubo, Z.; Yi, Z.; Jia, L.; Yi, C.; Yanfen, F.; Xiongwen, Z.; Wei, L. Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors. Eur. J. Med. Chem., 2015, 95, 127-135.
[41]
Hassanzadeh, M.; Bagherzadeh, K.; Amanlou, M. A comparative study based on docking and molecular dynamics simulations over HDAC-tubulin dual inhibitors. J. Mol. Graph. Model., 2016, 70, 170-180.
[42]
Zhang, X.; Zhang, J.; Su, M.; Zhou, Y.; Chen, Y.; Li, J.; Lu, W. Design, synthesis and biological evaluation of 4′-demethyl-4-deoxypodophyllotoxin derivatives as novel tubulin and histone deacetylase dual inhibitors. RSC Advances, 2014, 4, 40444-40448.
[43]
Liou, J.P.; Chang, Y.L.; Kuo, F.M.; Chang, C.W.; Tseng, H.Y.; Wang, C.C.; Yang, Y.N.; Chang, J.Y.; Lee, S.J.; Hsieh, H.P. Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents. J. Med. Chem., 2004, 47, 4247-4257.
[44]
Kuo, C.C.; Hsieh, H.P.; Pan, W.Y.; Chen, C.P.; Liou, J.P.; Lee, S.J.; Chang, Y.L.; Chen, L.T.; Chen, C.T.; Chang, J.Y. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res., 2004, 64, 4621-4628.
[45]
Hsueh, Y.L.; Jiann, F.L.; Sunil, K.; Yi, W.W.; Wei, C.F.; Mei, J.L.; Yu, H.L.; Hsiang, L.H.; Fei, C.K.; Che, J.H.; Chun, C.C.; Chia, R.Y.; Jing, P.L. 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity. Eur. J. Med. Chem., 2017, 125, 1268-1278.
[46]
Wei, C.H.; Min, W.C.; Chun, C.C.; Yu, C.W.; Yi, W.W.; Jing, P.L.; George, H.; Yu, C.L.; Chia, R.Y. Anti-leukemia effects of the novel synthetic 1-benzylindole derivative 21-900 in vitro and in vivo. Sci. Rep., 2017, 7, 42291-42303.
[47]
Seigneuric, R.; Mjahed, H.; Gobbo, J.; Joly, A.; Berthenet, K.; Shirley, S.; Garrido, C. Heat shock proteins as danger signals for cancer detection. Front. Oncol., 2011, 1, 1-10.
[48]
Kampinga, H.H.; Hageman, J.; Vos, M.J.; Kubota, H.; Tanguay, R.M.; Bruford, E.A.; Cheetham, M.E.; Chen, B.; Hightower, L.E. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones, 2009, 14, 105-111.
[49]
Joly, A.L.; Wettstein, G.; Mignot, G.; Ghiringhelli, F.; Garrido, C. Dual role of heat shock proteins as regulators of apoptosis and innate immunity. J. Innate Immun., 2010, 2, 238-247.
[50]
Calderwood, S.K.; Khaleque, M.A.; Sawyer, D.B.; Ciocca, D.R. Heat shock proteins in cancer: Chaperones of tumorigenesis. Trends Biochem. Sci., 2006, 31, 164-172.
[51]
Neckers, L.; Workman, P. Hsp90 molecular chaper-one inhibitors: Are we there yet? Clin. Cancer Res., 2012, 18, 64-76.
[52]
Meng, L.; Hunt, C.; Yaglom, J.A.; Gabai, V.L.; Sherman, M.Y. Heat shock protein Hsp72 plays an essential role in Her2-induced mammary tumorigenesis. Oncogene, 2011, 30, 2836-2845.
[53]
Kuo, C.C.; Hsieh, H.P.; Pan, W.Y.; Chen, C.P.; Liou, J.P.; Lee, S.J.; Chang, Y.L.; Chen, L.T.; Chen, C.T.; Chang, J.Y. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res., 2004, 64, 4621-4628.
[54]
Andrew, J.S.K.; Trevor, P.; Michal, P.; Georgia, G.; Christopher, T.F.; Darren, F.; Williams, D.C.; Meegan, M.J.; Lloyd, D.G. Integration of ligand and structure-based virtual screening for the identification of the first dual targeting agent for Heat Shock Protein 90 (Hsp90) and tubulin. J. Med. Chem., 2009, 52, 2177-2180.
[55]
Baoping, Y.; Guoyong, H.; Jieping, Y.; Zongxue, R.; Hesheng, L. Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line. Dig. Dis. Sci., 2004, 49, 948-953.
[56]
Elder, D.J.; Halton, D.E.; Hague, A.; Paraskeva, C. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: Independence from COX-2 protein expression. Clin. Cancer Res., 1997, 3, 1679-1683.
[57]
Hanif, R.; Pittas, A.; Feng, Y.; Koutsos, M.I.; Qiao, L.; Staiano-Coico, L.; Shiff, S.I.; Rigas, B. Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem. Pharmacol., 1996, 52, 237-245.
[58]
Johnson, A.J.; Song, X.; Hsu, A.; Chen, C. Apoptosis signaling pathways mediated by cyclooxygenase-2 inhibitors in prostate cancer cells. Adv. Enzyme Regul., 2001, 41, 221-235.
[59]
Pan, Y.; Zhang, J.S.; Gazi, M.H.; Young, C.Y. The cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c-Jun in prostate cancer cells. Cancer Epidemiol. Biomarkers Prev., 2003, 12, 769-774.
[60]
Shiff, S.J.; Koutsos, M.I.; Qiao, L.; Rigas, B. Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: Effects on cell cycle and apoptosis. Exp. Cell Res., 1996, 222, 179-188.
[61]
Zhong, B.; Cai, X.; Chennamaneni, S.; Yi, X.; Liu, L.; Pink, J.J.; Dowlati, A.; Xu, Y.; Zhou, A.; Su, B. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation. Eur. J. Med. Chem., 2012, 47, 432-444.
[62]
Yi, X.; Zhong, B.; Smith, K.M.; Geldenhuys, W.J.; Feng, Y.; Pink, J.J.A.; Dowlati, A.; Xu, Y.; Zhou, A.; Su, B. Identification of a class of novel tubulin inhibitors. J. Med. Chem., 2012, 55, 3425-3435.
[63]
Zhong, B.; Chennamaneni, S.; Lama, R.; Yi, X.; Geldenhuys, W.J.; Pink, J.J.; Dowlati, A.; Xu, Y.; Zhou, A.; Su, B. Synthesis and anticancer mechanism investigation of dual Hsp27 and tubulin inhibitors. J. Med. Chem., 2013, 56, 5306-5320.
[64]
Zhong, B.; Lama, R.; Kulman, D.G.; Li, B.; Su, B. Lead optimization of dual tubulin and Hsp27 inhibitors. Eur. J. Med. Chem., 2014, 80, 243-253.
[65]
Zhou, H.Y.; Wu, S.H.; Zhai, S.M.; Liu, A.F.; Sun, Y.; Li, R.S.; Zhang, Y.; Ekins, S.; Swaan, P.W.; Fang, B.; Zhang, B.; Yan, B. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J. Med. Chem., 2008, 51, 1242-1251.
[66]
Zhang, Q.; Zhai, S.; Li, L.; Li, X.; Zhou, H.; Liu, A.; Su, G.; Mu, Q.; Du, Y.; Yan, B. Anti-tumor selectivity of a novel Tubulin and HSP90 dual-targeting inhibitor in non-small cell lung cancer models. Biochem. Pharmacol., 2013, 86, 351-360.
[67]
Hargreaves, R.H.; David, C.L.; Whitesell, L.J.; Labarbera, D.V.; Jamil, A.; Chapuis, J.C.; Skibo, E.B. Discovery of quinolinediones exhibiting a heat shock response and angiogenesis inhibition. J. Med. Chem., 2008, 51, 2492-2501.
[68]
Nien, C.Y.; Chen, Y.C.; Kuo, C.C.; Hsieh, H.P.; Chang, C.Y.; Wu, J.S.; Wu, S.Y.; Liou, J.P.; Chang, J.Y. 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors. J. Med. Chem., 2010, 53, 2309-2313.
[69]
Nepali, K.; Kumar, S.; Huang, H.L.; Kuo, F.C.; Lee, C.H.; Kuo, C.C.; Yeh, T.K.; Li, Y.H.; Chang, J.Y.; Liou, J.P.; Lee, H.Y. 2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition. Org. Biomol. Chem., 2016, 14, 716-723.
[70]
Sengupta, S.K.; Foye, W.O. Inhibitors of DNA topoisomerases. In: Cancer Chemotherapeutic Agents; American Chemical Society: DC, 1995; pp. 205-217.
[71]
Wang, J.C. Cellular roles of DNA topoisomerases: A molecular perspective. Nat. Rev. Mol. Cell Biol., 2002, 3, 430-440.
[72]
Pommier, Y.; Leo, E.; Zhang, H.; Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol., 2010, 17, 421-433.
[73]
Chen, S.H.; Chan, N.L.; Hsieh, T.S. New mechanistic and functional insights into DNA topoisomerases. Annu. Rev. Biochem., 2013, 82, 139-170.
[74]
Champoux, J.J. DNA topoisomerases: Structure, function, and mechanism. Annu. Rev. Biochem., 2001, 70, 369-413.
[75]
Nitiss, J.L. DNA topoisomerase II and its growing repertoire of biological functions. Nat. Rev. Cancer, 2009, 9, 327-337.
[76]
Vos, S.M.; Tretter, E.M.; Schmidt, B.H.; Berger, J.M. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat. Rev. Mol. Cell Biol., 2011, 12, 827-841.
[77]
Ashour, M.E.; Atteya, R.; Khamisy, S.F.E. Topoisomerase-mediated chromosomal break repair: An emerging player in many games. Nat. Rev. Cancer, 2015, 15, 137-151.
[78]
Chang, J.Y.; Hsieh, H.P.; Pan, W.Y.; Liou, J.P.; Bey, S.J.; Chena, L.T.; Liu, J.F.; Song, J.S. Dual inhibition of topoisomerase I and tubulin polymerization by BPR0Y007, a novel cytotoxic agent. Biochem. Pharmacol., 2003, 65, 2009-2019.
[79]
Leon, L.G.; Luci, C.R.; Tejedor, D.; Roth, E.P.; Montero, J.C.; Pandiella, A.; Tellado, F.G.; Padron, J.M. Mitotic arrest induced by a novel family of DNA Topoisomerase II inhibitors. J. Med. Chem., 2010, 53, 3835-3839.
[80]
Renic, A.P.; Bankovic, J.; Dinic, J.; Luci, C.R.; Miguel, X.F.; Ortega, N.; Grujicic, N.K.; Victor, S.M.; Jose, M.P.; Pesic, M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. Eur. J. Pharm. Sci., 2017, 15, 159-168.
[81]
Diana, P.; Martorana, A.; Barraja, P.; Montalbano, A.; Dattolo, G.; Cirrincione, G.; Francesco, D.A.; Salvador, A.; Vedaldi, D.; Basso, G.; Viola, G. Isoindolo[2,1-a]quinoxaline derivatives, novel potent antitumor agents with dual inhibition of tubulin polymerization and topoisomerase I. J. Med. Chem., 2008, 51, 2387-2399.
[82]
Chiou, W.F.; Sung, Y.J.; Liao, J.F.; Shum, A.Y.; Chen, C.F. Inhibitory effect of dehydroevodiamine and evodiamine on nitric oxide production in cultured murine macrophages. J. Nat. Prod., 1997, 60, 708-711.
[83]
Ko, H.C.; Wang, Y.H.; Liou, K.T.; Chen, C.M.; Chen, C.H.; Wang, W.Y.; Chang, S.; Hou, Y.C.; Chen, K.T.; Chen, C.F.; Shen, Y.C. Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells. Eur. J. Pharmacol., 2007, 555, 211-217.
[84]
Kobayashi, Y.; Nakano, Y.; Kizaki, M.; Hoshikuma, K.; Yokoo, Y.; Kamiya, T. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med., 2001, 67, 628-633.
[85]
Jiang, J.; Hu, C. Evodiamine: A novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules, 2009, 14, 1852-1859.
[86]
Shengzheng, W.; Kun, F.; Guoqiang, D.; Shuqiang, C.; Na, L.; Zhenyuan, M.; Jianzhong, Y.; Jian, L.; Zhang, W.; Sheng, C. Scaffold diversity inspired by the natural product evodiamine: Discovery of highly potent and multitargeting antitumor agents. J. Med. Chem., 2015, 58, 6678-6696.
[87]
Guerrant, W.; Patil, V.; Canzoneri, J.C.; Oyelere, A.K. Dual targeting of histone deacetylase and topoisomerase II with novel bifunctional inhibitors. J. Med. Chem., 2012, 55, 1465-1477.
[88]
Zhang, R.; Li, Y.; Cai, Q.; Liu, T.H.; Sun, B. Chambless, Preclinical pharmacology of the natural products anticancer agents 10-hydroxyxamptothecin, an inhibitor of topoisomerase I. Cancer Chemother. Pharmacol., 1998, 41, 257-267.
[89]
Chen, Z.S.; Furukawa, T.; Sumizawa, T.; Ono, K.; Ueda, K.; Seto, K.; Akiyama, S.I. ATP-dependent efflux of CPT-11 and SN-38 by the Multidrug Resistance Protein (MRP) and its inhibition by PAK-104P. Mol. Pharmacol., 1999, 55, 921-928.
[90]
Sugimori, M.; Ejima, A.; Ohsuki, S.; Uoto, K.; Mitsui, I.; Matsumoto, K.; Kawato, Y.; Yasuoka, M.; Sato, M.; Tagawa, H.; Terasawa, H. Synthesis and antitumor activity of novel hexacyclic camptothecin analogues. J. Med. Chem., 1994, 37, 3033-3039.
[91]
Leu, Y.L.; Chen, C.S.; Wu, Y.J.; Chern, J.W. Benzyl ether-linked glucuronide derivative of 10-hydroxycamptothecin designed for selective camptothecin-based anticancer therapy. J. Med. Chem., 2008, 51, 1740; (b) Ulukan, H.; Swaan, P.W. Camptothecins: A review of their chemotherapeutic potential. Drugs, 2002, 6, 2039-2057.
[92]
Guerrant, W.; Patil, V.; Canzoneri, J.C.; Yao, L.P.; Hood, R.; Oyelere, A.K. Dual-acting histone deacetylase-topoisomerase I inhibitors. Bioorg. Med. Chem. Lett., 2013, 23, 3283-3287.
[93]
Zhang, X.; Bao, B.; Yu, X.; Tong, L.; Luo, Y.; Huang, Q.; Su, M.; Sheng, L.; Li, J.; Zhu, H.; Yang, B.; Zhang, X.; Chen, Y.; Lu, W. The discovery and optimization of novel dual inhibitors of topoisomerase II and histone deacetylase. Bioorg. Med. Chem., 2013, 21, 6981-6995.
[94]
Yu, C.C.; Pan, S.L.; Chao, S.W.; Liu, S.P.; Hsu, J.L.; Yang, Y.C.; Li, T.K.; Huang, W.J.; Guh, J.H. A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I. Biochem. Pharmacol., 2014, 90, 320-330.
[95]
He, S.; Dong, G.; Wang, Z.; Chen, W.; Huang, Y.; Li, Z.; Jiang, Y.; Liu, N.; Yao, J.; Miao, Z.; Zhang, W.; Sheng, C. Discovery of novel multiacting topoisomerase I/II and histone deacetylase inhibitors. ACS Med. Chem. Lett., 2015, 6, 239-243.
[96]
Manning, G.; Whyte, D.B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298, 1912-1934.
[97]
Stehelin, D.; Varmus, H.E.; Bishop, J.M.; Vogt, P.K. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature, 1976, 260, 170-173.
[98]
Hunter, T.; Cooper, J.A. Protein-tyrosine kinases. Annu. Rev. Biochem., 1985, 54, 897-930.
[99]
Krishnegowda, G.; Gowda, A.S.P.; Tagaram, H.R.S.; Carroll, O.K.F.; Irby, R.B.; Sharma, A.K.; Amin, S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg. Med. Chem., 2011, 19, 6006-6014.
[100]
Guo, L.; Liu, X.; Nishikawa, K.; Plunkett, W. Inhibition of topoisomerase II alpha and G2 cell cycle arrest by NK314, a novel benzo[c]phenanthridine currently in clinical trials. Mol. Cancer Ther., 2007, 6, 1501-1508.
[101]
Onda, T.; Toyoda, E.; Miyazaki, O.; Seno, C.; Kagaya, S.; Okamoto, K.; Nishhikawa, K. NK314, a novel topoisomerase II inhibitor, induces rapid DNA double-strand breaks and exhibits superior antitumor effects against tumors resistant to other topoisomerase II inhibitors. Cancer Lett., 2008, 259, 99-110.
[102]
Toyoda, E.; Kagaya, S.; Cowell, I.G.; Kurosawa, A.; Kamoshita, K.; Nishikawa, K.; Iiizumi, S.; Koyama, H.; Austin, C.A.; Adachi, N. NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. J. Biol. Chem., 2008, 283, 23711-23720.
[103]
Takashi, H.; Naoko, S.A.; Akemi, S.; Rika, T.; Masaru, I.; Akihiro, K.; Kazuya, O.; Shinya, K.; Eisaburo, S. NK314 potentiates antitumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIα and DNA-dependent protein kinase. Blood, 2011, 117, 3575-3584.
[104]
Qian, C.; Lai, C.J.; Bao, R.; Wang, D.G.; Wang, J.; Xu, G.X.; Atoyan, R.; Qu, H.; Yin, L.; Samson, M.; Zifcak, B.; Ma, A.W.S.; Rocca, S.D.; Borek, M.; Zhai, H.X.; Cai, X.; Voi, M. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin. Cancer Res., 2012, 18, 4104-4113.
[105]
Nakanishi, T.; Shiozawa, K.; Hassel, B.A.; Ross, D.D. Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib induced reduction of BCRP expression. Blood, 2006, 108, 678-684.
[106]
Hegedus, C.; Ozvegy Laczka, C.; Apati, A.; Magocsi, M.; Nemet, K.; Orfi, L.; Keri, G.; Katona, M.; Takats, Z.; Varadi, A.; Szakacs, G.; Sarkadi, B. Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: Implications for altered anti-cancer effects and pharmacological properties. Br. J. Pharmacol., 2009, 158, 1153-1164.
[107]
Burger, H.; Tol, H.V.; Brok, M.; Wiemer, E.A.; Bruijn, E.A.; Guetens, G.; Boeck, G.; Sparreboom, A.; Verweij, J.; Nooter, K. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol. Ther., 2005, 4, 747-752.
[108]
Mahon, F.X.; Belloc, F.; Lagarde, V.; Chollet, C.; Gaudry, F.M.; Reiffers, J.; Goldman, J.M.; Melo, J.V. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood, 2003, 101, 2368-2373.
[109]
Thomas, J.; Wang, L.; Clark, R.E.; Pirmohamed, M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood, 2004, 104, 3739-3745.
[110]
Wu, C.P.; Hsieh, Y.J.; Hsia, S.H.; Su, C.Y.; Li, Y.Q.; Huang, Y.H.; Huang, C.W.; Hsieh, C.H.; Yu, J.S.; Wu, Y.S. Human ATP-binding cassette transporter ABCG2 confers resistance to CUDC-907, a dual inhibitor of histone deacetylase and phosphatidylinositol 3-kinase. Mol. Pharm., 2016, 13, 784-794.
[111]
Younes, A.; Berdeja, J.G.; Patel, M.R.; Flinn, I.; Gerecitano, J.F.; Neelapu, S.S.; Kelly, K.R.; Copeland, A.R.; Akins, A.; Clancy, M.S.; Gong, L.; Wang, J.; Ma, A.; Viner, J.L.; Oki, Y. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: An open-label, dose-escalation, phase 1 trial. Lancet Oncol., 2016, 17, 622-631.
[112]
Zhang, X.; Su, M.; Chen, Y.; Li, J.; Lu, W. The design and synthesis of a new class of RTK/HDAC dual-targeted inhibitors. Molecules, 2013, 18, 6491-6503.
[113]
Zhao, Y.; Su, J.; Goto, M.; Natschke, S.L.M.; Li, Y.; Zhao, Q.S.; Yao, Z.J.; Lee, K.H. Dual-functional abeo-taxane derivatives destabilizing microtubule equilibrium and inhibiting NF-κB activation. J. Med. Chem., 2013, 56, 4749-4757.
[114]
Zhou, H.Y.; Wu, S.H.; Zhai, S.M.; Liu, A.F.; Sun, Y.; Li, R.S.; Zhang, Y.; Ekins, S.; Swaan, P.W.; Fang, B.L.; Zhang, B.; Yan, B. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J. Med. Chem., 2008, 51, 1242-1251.
[115]
Li, L.; Zhang, Q.; Liu, A.; Li, X.; Zhou, H.; Liu, Y.; Yan, B. Proteome interrogation using nanoprobes to identify targets of a cancer-killing molecule. J. Am. Chem. Soc., 2011, 133, 6886-6889.
[116]
Zhang, Q.; Zhai, S.; Li, L.; Li, X.; Zhou, H.; Liu, A.; Su, G.; Mu, Q.; Du, Y.; Yan, B. Anti-tumor selectivity of a novel Tubulin and HSP90 dual-targeting inhibitor in non-small cell lung cancer models. Biochem. Pharmacol., 2013, 86, 351-360.
[117]
Li, L.; Liu, Y.; Zhang, Q.; Zhou, H.; Zhang, Y.; Yan, B. Comparison of cancer cell survival triggered by microtubule damage after turning Dyrk1B kinase on and off. ACS Chem. Biol., 2014, 9, 731-742.
[118]
Zhang, X.; Raghavan, S.; Ihnat, M.; Thorpe, J.E.; Disch, B.C.; Bastian, A.; Downs, L.C.; Hargreaves, N.F.D.; Rohena, C.C.; Hamel, E.; Mooberry, S.L.; Gangjee, A. The design and discovery of water soluble 4-substituted-2, 6-dimethylfuro[2,3-d]pyrimidines as multitargeted receptor tyrosine kinase inhibitors and microtubule targeting antitumor agents. Bioorg. Med. Chem., 2014, 22, 3753-3772.
[119]
Peng, T.; Wu, J.R.; Tong, L.J.; Li, M.Y.; Chen, F.; Leng, Y.X.; Qu, R.; Han, K.; Su, Y.; Chen, Y.; Duan, W.H.; Xie, H.; Ding, J. Identification of DW532 as a novel anti-tumor agent targeting both kinases and tubulin. Acta Pharmacol. Sin., 2014, 35, 916-928.
[120]
Niino, M.K.; Tokmakoz, A.; Terada, T.; Ohbayashi, N.; Fujimoto, T.; Gomi, S.; Shiromizu, I.; Kawamoto, M.; Matsusue, T.; Shirouzu, M.; Yokoyama, S. Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4. Biol. Crystallogr., 2011, 67, 763-773.
[121]
Meng, T.; Zhang, D.; Xie, Z.; Yu, T.; Wu, S.; Wyder, L.; Regenass, U.; Hilpert, K.; Huang, M.; Geng, M.; Shen, J. Discovery and optimization of 4,5-diarylisoxazoles as potent dual inhibitors of pyruvate dehydrogenase kinase and heat shock protein 90. J. Med. Chem., 2014, 57, 9832-9843.
[122]
Zhou, M.; Ning, C.; Liu, R.; He, Y.; Yu, N. Design, synthesis and biological evaluation of indeno[1,2-d]thiazole derivatives as potent histone deacetylase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23, 3200-3203.
[123]
Ning, C.; Bi, Y.; He, Y.; Huang, W.; Liu, L.; Li, Y.; Zhang, S.; Liu, X.; Yu, N. Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23, 6432-6435.
[124]
William, A.D.; Lez, A.C.H.; Blanchard, S.; Poulsen, A.; Teo, E.L.; Nagaraj, H.; Tan, E.; Chen, D.; Williams, M.; Sun, E.T.; Goh, K.C.; Ong, W.C.; Goh, S.K.; Hart, S.; Jayaraman, R.; Pasha, M.K.; Ethirajulu, K.; Wood, J.M.; Dymock, B.W. Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)] heptacosa-1(25),2(26),3, 5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J. Med. Chem., 2011, 54, 4638-4658.
[125]
Ning, C.Q.; Lu, C.; Hu, L.; Bi, Y.J.; Yao, L.; He, Y.J.; Liu, L.F.; Liu, X.Y.; Yu, N.F. Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2. Eur. J. Med. Chem., 2015, 95, 104-115.
[126]
Zhang, X.; Raghavan, S.; Ihnat, M.; Hamel, E.; Zammiello, C.; Bastian, A.; Mooberry, S.L.; Gangjee, A. The design, synthesis and biological evaluation of conformationally restricted 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as multi-targeted receptor tyrosine kinase and microtubule inhibitors as potential antitumor agents. Bioorg. Med. Chem., 2015, 23, 2408-2423.
[127]
Mahalel, S.; Bharate, S.B.; Manda, S.; Joshi, P.; Jenkins, P.R.; Vishwakarma, R.A.; Chaudhuri, B. Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization. Cell Death Dis., 2015, 6, 1743-1755.
[128]
Ferlin, M.G.; Chiarelotto, G.; Gasparotto, V.; Dalla Via, L.; Pezzi, V.; Barzon, L.; Palu, G.; Castagliuolo, I. Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones. J. Med. Chem., 2005, 48, 3417-3427.
[129]
Gasparotto, V.; Castagliuolo, I.; Chiarelotto, G.; Pezzi, V.; Montanaro, D.; Brun, P.; Palu, G.; Viola, G.; Ferlin, M.G. Synthesis and biological activity of 7-phenyl-6,9-dihydro-3H-pyrrolo[3,2-f] quinolin-9-ones: A new class of antimitotic agents devoid of aromatase activity. J. Med. Chem., 2006, 49, 1910-1915.
[130]
Carta, D.; Bortolozzi, R.; Hamel, E.; Basso, G.; Moro, S.; Viola, G.; Ferlin, M.G. Novel 3-substituted 7-phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as single entities with multitarget antiproliferative activity. J. Med. Chem., 2015, 58, 7991-8010.
[131]
Cao, R.; Liu, M.; Yin, M.; Liu, Q.; Wang, Y.; Huang, N. Discovery of novel tubulin inhibitors via structure-based hierarchical virtual screening. J. Chem. Inf. Model., 2012, 52, 2730-2740.
[132]
Cao, R.; Wang, Y.; Huang, N. Discovery of 2-acylaminothiophene-3-carboxamides as multitarget inhibitors for BCR-ABL kinase and microtubules. J. Chem. Inf. Model., 2015, 55, 2435-2442.
[133]
Purwin, M.; Toribio, J.H.; Coderch, C.; Panchuk, R.; Skorokhyd, N.; Filipiak, K.; Pascual-Teresa, B.D.; Ramos, A. Design and synthesis of novel dual-target agents for HDAC1 and CK2 inhibition. RSC Advances, 2016, 6, 66595-66608.
[134]
Cai, X.; Zhai, H.X.; Wang, J.; Forrester, J.; Qu, H.; Yin, L.; Lai, C.J.; Bao, R.; Qian, C. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)- N-hydroxy heptanamide (CUDC-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J. Med. Chem., 2010, 53, 2000-2009.
[135]
Yang, E.G.; Mustafa, N.; Tan, E.C.; Poulsen, A.; Ramanujulu, P.M.; Chng, W.J.; Yen, J.J.Y.; Dymock, B.W. Design and synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) bispecific inhibitors based on pacritinib and evidence of dual pathway inhibition in hematological cell lines. J. Med. Chem., 2016, 59, 8233-8262.
[136]
Morioka, M. 3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of Aurora kinase and tubulin polymerization. Bioorg. Med. Chem. Lett., 2016, 26, 5860-5862.
[137]
Maira, S.M.; Pecchi, S.; Huamg, A.; Burger, M.; Knapp, M.; Sterker, D.; Schnell, C.; Guthy, D.; Nagal, T.; Wiesmann, M.; Brachmann, S.; Fritsch, C.; Dorsch, M.; Chene, P.; Shoemaker, K.; Pover, A.; Menezes, D.; Martiny Baron, G.; Fabbro, D.; Wilson, C.J.; Schlegel, R.; Hofmann, F.; Garcia Echeverria, C.; Sellers, W.R.; Voliva, C.F. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol. Cancer Ther., 2012, 11, 317-328.
[138]
Burger, M.T.; Pecchi, S.; Burger, M.T.; Wagman, A.; Ni, Z.J.; Knapp, M.; Hendrickson, T.; Atallah, G.; Pfister, K.; Zhang, Y.; Bartulis, S.; Frazier, K.; Ng, S.; Smith, A.; Verhagen, J.; Haznedar, J.; Huh, K.; Iwanowicz, E.; Xin, X.; Menezes, D.; Merritt, H.; Lee, I.; Wiesmann, M.; Kaufmann, S.; Crawford, K.; Chin, M.; Bussiere, D.; Shoemaker, K.; Zaror, I.; Maira, S.M.; Voliva, C.F. Identification of NVP-BKM120 as a potent, selective, orally bioavailable class I PI3 kinase inhibitor for treating cancer. ACS Med. Chem. Lett., 2011, 2, 774-779.
[139]
Massacesi, C.; Tomaso, E.; Fretault, N.; Hirawat, S. Challenges in the clinical development of PI3K inhibitors. Ann. N. Y. Acad. Sci., 2013, 1280, 19-23.
[140]
Saura, C.; Bendell, J.; Jerusalem, G.; Su, S.; Ru, Q.; Buck, S.D.; Mills, D.; Requet, S.; Bosch, A.; Urruticoechea, A.; Beck, J.T.; Tomaso, E.D.; Sternberg, D.W.; Massacesi, C.; Hirawat, S.; Dirix, L.; Baselga, J. Phase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy. Clin. Cancer Res., 2014, 20, 1935-1945.
[141]
Brachmann, S.M.; Kleylein Sohn, J.; Gaulis, S.; Kauffmann, A.; Blommers, M.J.; Kaziclegueux, M.; Laborde, L.; Hattenberger, M.; Stauffer, F.; Vaxelaire, J.; Romanet, V.; Henry, C.; Maurakami, M.; Guthy, D.A.; Sterker, D.; Bergling, S.; Wilson, C.; Brummendorf, T.; Fritsch, C.; Garcia Echeverria, C.; Sellers, W.R.; Hofmann, F.; Maira, S.M. Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations. Mol. Cancer Ther., 2012, 11, 1747-1757.
[142]
Andrea, E.T.B.; John, E.P.F.B.; Alison, J.B.A.M.; Alexander, M.I.D.R.; Vladimir, C.; Cmiljanovic, N.; Bargsten, K.; Aher, A.; Akhmanova, A.; Dıaz, J.F.; Fabbro, D.; Zvelebil, M.; Roger, L.; Michel, O.W.; Matthias Wymann, P.S. Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention. Nat. Commun., 2017, 8, 14683.
[143]
Sk, U.K.; Gowda, A.S.; Crampsie, M.A.; Yun, J.K.; Spratt, T.E.; Amin, S.; Sharma, A.K. Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics. Eur. J. Med. Chem., 2011, 46, 3331-3338.
[144]
Sharma, A.K.; Sharma, A.; Desai, D.; Madhunapantula, S.V.; Huh, S.J.; Robertson, G.P.; Amin, S. Synthesis and anticancer activity comparison of phenylalkyl isoselenocyanates with corresponding naturally occurring and synthetic isothiocyanates. J. Med. Chem., 2008, 51, 7820-7826.
[145]
Karelia, D.N. SK, U.H.; Singh, P.; Gowda, A.S.P.; Pandey, M.K.; Ramisetti, S.R.; Amin, S.; Sharma, A.K.; Design, synthesis, and identification of a novel napthalamideisoselenocyanate compound NISC-6 as a dual Topoisomerase-IIa and Akt pathway inhibitor, and evaluation of its anti-melanoma activity. Eur. J. Med. Chem., 2017, 135, 282-295.
[146]
Li, Y.; Luo, X.; Guo, Q.; Nie, Y.; Wang, T.T.; Zhang, C.; Huang, Z.; Wang, X.; Liu, Y.; Chen, Y.; Zheng, J.; Yang, S.; Fan, Y.; Xiang, R. Discovery of N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxy octanediamide as a novel inhibitor targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against malignant cancer. J. Med. Chem., 2018, 61, 3166-3192.
[147]
Huang, Y.; Dong, G.; Li, H.; Liu, N.; Zhang, W.; Sheng, C. Discovery of Janus Kinase 2 (JAK2) and Histone Deacetylase (HDAC) dual inhibitors as a novel strategy for combinational treatment of leukemia and invasive fungal infections. J. Med. Chem., 2018, 61(14), 6056-6074.
[148]
Trippier, P.C.; Labby, K.J.; Hawker, D.D.; Mataka, J.J.; Silverman, R.B. Target- and mechanism-based therapeutics for neurodegenerative diseases: Strength in numbers. J. Med. Chem., 2013, 56, 3121-3147.
[149]
Kinarivala, N.; Patel, R.; Boustany, R.M.; Al-Ahmad, A.; Trippier, P.C. Discovery of aromatic carbamates that confer neuroprotective activity by enhancing autophagy and inducing the anti-apoptotic protein B-Cell lymphoma 2 (Bcl-2). J. Med. Chem., 2017, 60, 9739-9756.
[150]
Morphy, R.; Rankovic, Z. Designed multiple ligands. an emerging drug discovery paradigm. J. Med. Chem., 2005, 48, 6523-6543.
[151]
Geldenhuys, W.J.; Van der Schyf, C.J. Rationally designed multi-targeted agents against neurodegenerative diseases. Curr. Med. Chem., 2013, 20, 1662-1672.