Recent Advances in Apoptosis: THE Role of Hydrazones

Author(s): Pelin Çıkla-Süzgün, Ş. Güniz Küçükgüzel*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 17 , 2019


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

The process of programmed cell death in higher eukaryotes (apoptosis), is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered as a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Apoptosis seems to play an important key role in the progression of several human diseases like Alzheimer's disease, Parkinson's disease and many types of cancer. Promotion of apoptosis may be a good approach for the prevention of cancer cell proliferation. In early studies, antitumor compounds have been found to induce the apoptotic process in tumor cells. On the other hand, several hydrazones were reported to have lower toxicity than hydrazides due to the blockage of –NH2 group. Therefore, the design of hydrazones that activate and promote apoptosis is an attractive strategy for the discovery and development of potential anticancer agents. The aim of this review is to provide a general overview of current knowledge and the connection between apoptosis and hydrazone. It is also the guide for the apoptotic activities of new hydrazone derivatives.

Keywords: Apoptosis, hydrazone, cancer, caspase-8, caspase-3, Bcl-2.

[1]
Kerr, J.F.; Wyllie, A.H.; Currie, A.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 1972, 26, 239-257.
[2]
Paweletz, N. Walther Flemming: Pioneer of mitosis research. Nat. Rev. Mol. Cell Biol., 2001, 2, 72-75.
[3]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[4]
Horvitz, H.R. Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res., 1999, 59, 1701-1706.
[5]
Formigli, L.; Papucci, L.; Tani, A.; Schiavone, N.; Tempestini, A.; Orlandini, G.E.; Capaccioli, S.; Orlandini, S.Z. Aponecrosis: morphological and biochemical exploration of a syncreticprocess of cell death sharing apoptosis and necrosis. J. Cell. Physiol., 2000, 182, 41-49.
[6]
Sperandio, S.; de Belle, I.; Bredesen, D.E. An alternative, nonapoptotic form of programmed cell death. Proc. Natl. Acad. Sci. USA, 2000, 97, 14376-14381.
[7]
Debnath, J.; Baehrecke, E.H.; Kroemer, G. Does autophagy contribute to cell death? Autophagy, 2005, 1, 66-74.
[8]
Norbury, C.J.; Hickson, I.D. Cellular responses to DNA damage. Annu. Rev. Pharmacol. Toxicol., 2001, 41, 367-401.
[9]
Kerr, J.F.R.; Harmon, B.V. Definition and incidence of apoptosis: An historical perspective. In: Apoptosis: The molecular basis of cell death; Tomei, L.D.; Cope, F.O., Eds.; Cold Spring Harbor Laboratory Press: New York, 1991; Vol. 3, pp. 5-29.
[10]
Fadeel, B.; Orrenius, S.; Zhivotovsky, B. Apoptosis in human disease: A new skin for the old ceremony? Biochem. Biophys. Res. Commun., 1999, 266, 699-717.
[11]
Fanidi, A.; Harrington, E.A.; Evan, G.I. Cooperative interaction between c-myc and bcl-2 proto-oncogene. Nature, 1992, 359, 554-556.
[12]
Raff, M.C. Social controls on cell survival and cell death. Nature, 1992, 356, 397-400.
[13]
Evan, G.I.; Vousden, K.H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411, 342-348.
[14]
Miyashita, T.; Reed, J.C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell, 1995, 80, 293-299.
[15]
Soengas, M.S.; Alarcon, R.M.; Yoshida, H.; Giaccia, A.J.; Hakem, R.; Mak, T.W.; Lowe, S.W. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science, 1999, 284, 156-159.
[16]
Owen-Schaub, L.B.; Zhang, W.; Cusack, J.C.; Angelo, L.S.; Santee, S.M.; Fujiwara, T.; Roth, J.A.; Deisseroth, A.B.; Zhang, W.W.; Kruzel, E. Wild-type human p53 and a temperature sensitive mutant induce Fas/APO-1 expression. Mol. Cell. Biol., 1995, 15, 3032-3040.
[17]
Sheikh, M.S.; Burns, T.F.; Huang, Y.; Wu, G.S.; Amundson, S.; Brooks, K.S.; Fornace, A.J., Jr; el Deiry, W.S. p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. Cancer Res., 1998, 58, 1593-1598.
[18]
Levine, A.J. p53, The cellular gatekeeper for growth and division. Cell, 1997, 88, 323-331.
[19]
Schwartz, D.; Rotter, V. p53-dependent cell cycle control: response to genotoxic stress. Semin. Cancer Biol., 1998, 8, 325-336.
[20]
Akşit, H.; Bildik, A. Apoptozis, YYÜ Vet. Fak. Derg., 2008, 19, 55-63.
[21]
Teitz, T.; Wei, T.; Valentine, M.B.; Vanin, E.F.; Grenet, J.; Valentine, V.A.; Behm, F.G.; Look, A.T.; Lahti, J.M.; Kidd, V.J. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat. Med., 2000, 6, 529-535.
[22]
Soung, Y.H.; Lee, J.W.; Kim, S.Y.; Jang, J.; Park, Y.G.; Park, W.S.; Nam, S.W.; Lee, J.Y.; Yoo, N.J.; Lee, S.H. Caspase-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res., 2005, 65, 815-821.
[23]
Li, F.; Ambrosini, G.; Chu, E.Y.; Plescia, J.; Tognin, S.; Marchisio, P.C.; Altieri, D.C. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396, 580-584.
[24]
Li, F. Role of survivin and its splice variants in tumorigenesis. Br. J. Cancer, 2005, 92, 212-216.
[25]
Reed, J.C.; Miyashita, T.; Takayama, S.; Wang, H.G.; Sato, T.; Krajewski, S.; Aime, S.C.; Bodrug, S.; Kitada, S.; Hanada, M. BcL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J. Cell. Biochem., 1996, 60, 23-32.
[26]
Tsujii, M.; DuBois, R.N. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell, 1995, 83(3), 493-501.
[27]
Thesis Kern, M.A.; Schubert, D.; Sahi, D.; Schöneweiss, M.M.; Moll, I.; Haugg, A.M.; Dienes, H.P.; Breuhahn, K.; Schirmacher, P. Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells. Hepatology, 2002, 36, 885-894.
[28]
Kroemer, G.; Reed, J.C. Mitochondrial control of cell death. Nat. Med., 2000, 6, 513-519.
[29]
Fahy, B.N.; Schlieman, M.G.; Mortenson, M.M.; Virudachalam, S.; Bold, R.J. Targeting BcL-2 overexpression in various human malignancies through NF-kappaB inhibition by the proteasome inhibitor bortezomib. Cancer Chemother. Pharmacol., 2005, 56, 46-54.
[30]
Çıkla, P.; Özsavcı, D.; Bingöl-Özakpınar, Ö.; Şener, A.; Çevik, Ö.; Özbaş-Turan, S.; Akbuğa, J.; Şahin, F.; Küçükgüzel, Ş.G. Synthesis, cytotoxicity, and pro-apoptosis activity of etodolac hydrazide derivatives as anticancer agents. Arch. Pharm. (Weinheim), 2013, 346(5), 367-379.
[31]
Aydın, S.; Kaushik-Basu, N.; Özbaş-Turan, S.; Akbuğa, J.; Mega Tiber, P.; Orun, O.; Gurukumar, K.R.; Basu, A.; Küçükgüzel, Ş.G. Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as anti-HCV and anticancer agent. Lett. Drug Des. Discov., 2014, 11, 121-131.
[32]
Rollas, S.; Küçükgüzel, Ş.G. Biological activities of hydrazone derivatives. Molecules, 2007, 12, 1910-1939.
[33]
Deep, A.; Jain, S.; Sharma, P.C.; Verma, P.; Kumar, M.; Dora, C.P. Design and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activity. Acta Pol. Pharm., 2010, 67(3), 255-259.
[34]
Szarvasi, E.; Fontaine, L.; Betbeder-Matibet, A. Antimicrobials. New nitrofuran derivatives. J. Med. Chem., 1973, 16(3), 281-287.
[35]
Turan-Zitouni, G.; Kaplancıklı, Z.A. 5-Acetylindan aryloxyacetohydrazone derivatives: Synthesis and antituberculosis activity. Acta Pharm. Turc., 1998, 2, 67-71.
[36]
Metwally, K.A.; Abdel-Aziz, L.M.; Lashine, E.M.; Husseiny, M.I.; Badawy, R.H. Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: Synthesis and preliminary evaluation as antimicrobial agents. Bioorg. Med. Chem., 2006, 14(24), 8675-8682.
[37]
Singh, V.; Srivastava, V.K.; Palit, G.; Shanker, K. Coumarin congeners as antidepressants. Arzneim-Forsch Drug Res, 1992, 42(8), 993-999.
[38]
Easmon, J.; Puerstinger, G.; Roth, T.; Fiebig, H.H.; Jenny, M.; Jaeger, W.; Heinisch, G.; Hofmann, J. 2-benzoxazolyl and 2-benzimidazolyl hydrazones derived from 2-acetylpyridine: A novel class of antitumor agents. Int. J. Cancer, 2001, 94, 89-96.
[39]
De Graaf, A.O.; Van den Heuvel, L.P.; Dijkman, H.B.; De Abreu, R.A.; Birkenkamp, K.U.; De Witte, T.; Van der Reijden, B.A.; Smeitink, J.A.; Jansen, J.H. BcL-2 prevents loss of mitochondria in CCCP-induced apoptosis. Exp. Cell Res., 2004, 299(2), 533-540.
[40]
Zhang, H.Z.; Drewe, J.; Tseng, B.; Kasibhatla, S.; Cai, S.X. Discovery and SAR of indole-2-carboxylic acid benzylidene-hydrazides as a new series of potent apoptosis inducers using a cell-based HTS assay. Bioorg. Med. Chem., 2004, 12(13), 3649-3655.
[41]
Putt, K.S.; Chen, G.W.; Pearson, J.M.; Sandhorst, J.S.; Hoagland, M.S.; Kwon, J.T.; Hwang, S.K.; Jin, H.; Churchwell, M.I.; Cho, M.H.; Doerge, D.R.; Helferich, W.G.; Hergenrother, P.J. Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy. Nat. Chem. Biol., 2006, 2(10), 543-550.
[42]
Aziz, G.; Akselsen, Ø.W.; Hansen, T.V.; Paulsen, R.E. Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons. Toxicol. Appl. Pharmacol., 2010, 247(3), 238-242.
[43]
Peterson, Q.P.; Hsu, D.C.; Novotny, C.J.; West, D.C.; Kim, D.; Schmit, J.M.; Dirikolu, L.; Hergenrother, P.J.; Fan, T.M. Discovery and canine preclinical assessment of a nontoxic procaspase-3-activating compound. Cancer Res., 2010, 70, 7232-7241.
[44]
Peterson, Q.P.; Hsu, D.C.; Goode, D.R.; Novotny, C.J.; Totten, R.K.; Hergenrother, P.J. Procaspase-3 activation as an anti-cancer strategy: Structure-activity relationship of procaspase-activating compound 1 (PAC-1) and its cellular co-localization with caspase-3. J. Med. Chem., 2009, 52(18), 5721-5731.
[45]
Vogel, S.; Kaufmann, D.; Pojarová, M.; Müller, C.; Pfaller, T.; Kühne, S.; Bednarski, P.J.; Von Angerer, E. Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents. Bioorg. Med. Chem., 2008, 16(12), 6436-6447.
[46]
Zheng, L.W.; Wu, L.L.; Zhao, B.X.; Dong, W.L.; Miao, J.Y. Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells. Bioorg. Med. Chem., 2009, 17(5), 1957-1962.
[47]
Zhao, Y.; Hui, J.; Wang, D.; Zhu, L.; Fang, J.H.; Zhao, X.D. Synthesis, cytotoxicity and pro-apoptosis of novel benzoisoindolin hydrazones as anticancer agents. Chem. Pharm. Bull. (Tokyo), 2010, 58(10), 1324-1327.
[48]
Wirries, A.; Breyer, S.; Quint, K.; Schobert, R.; Ocker, M. Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells. Exp. Ther. Med., 2010, 2, 369-375.
[49]
Effenberger, K.; Breyer, S.; Ocker, M.; Schobert, R. New doxorubicin N-acyl hydrazones with improved efficacy and cell line specificity show modes of action different from the parent drug. Int. J. Clin. Pharmacol. Ther., 2010, 48(7), 485-486.
[50]
Effenberger, K.; Breyer, S.; Schobert, R. Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl and terpenyl hydrazones. Eur. J. Med. Chem., 2010, 45(5), 1947-1954.
[51]
Bak, Y.; Kim, H.; Kang, J.W.; Lee, D.H.; Kim, M.S.; Park, Y.S.; Kim, J.H.; Jung, K.Y.; Lim, Y.; Hong, J.; Yoon, D.Y. A synthetic naringenin derivative, 5-hydroxy-7,4′-diacetyloxyflavanone-N-phenyl hydrazone (N101-43), induces apoptosis through up-regulation of Fas/FasL expression and inhibition of PI3K/Akt signaling pathways in non-small-cell lung cancer cells. J. Agric. Food Chem., 2011, 59(18), 10286-102897.
[52]
Zulkepli, N.A.; Rou, K.V.; Sulaiman, W.N.; Salhin, A.; Saad, B.; Seeni, A. A synthetic hydrazone derivative acts as an apoptotic inducer with chemopreventive activity on a tongue cancer cell line. Asian Pac. J. Cancer Prev., 2011, 12, 259-263.
[53]
Lou, J.; Liu, Z.; Li, Y.; Zhou, M.; Zhang, Z.; Zheng, S.; Wang, R.; Li, J. Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives. Bioorg. Med. Chem. Lett., 2011, 21(22), 6662-6666.
[54]
Han, Y.H.; Yang, Y.M.; Park, W.H. Carbonyl cyanide p-(trifluoromethoxy) phenylhydroazone induces caspase-independent apoptosis in As4.1 juxtaglomerular cells. Anticancer Res., 2010, 30(7), 2863-2868.
[55]
Han, Y.H.; Park, W.H. Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells. Int. J. Mol. Med., 2011, 27(4), 575-581.
[56]
Hassan, G.S.; Kadry, H.H.; Abou-Seri, S.M.; Ali, M.M.; Mahmoud, A.E. Synthesis and in vitro cytotoxic activity of novel pyrazolo[3,4-d]pyrimidines and related pyrazole hydrazones toward breast adenocarcinoma MCF-7 cell line. Bioorg. Med. Chem., 2011, 19(22), 6808-6817.
[57]
Quattrocelli, M.; Palazzolo, G.; Agnolin, I.; Martino, S.; Bouché, M.; Anastasia, L.; Sampaolesi, M. Synthetic sulfonyl-hydrazone-1 positively regulates cardiomyogenic microRNA expression and cardiomyocyte differentiation of induced pluripotent stem cells. J. Cell. Biochem., 2011, 112(8), 2006-2014.
[58]
Dandawate, P.; Khan, E.; Padhye, S.; Gaba, H.; Sinha, S.; Deshpande, J.; Venkateswara, S.K.; Khetmalas, M.; Ahmad, A.; Sarkar, F.H. Synthesis, characterization, molecular docking and cytotoxic activity of novel plumbagin hydrazones against breast cancer cells. Bioorg. Med. Chem. Lett., 2012, 22(9), 3104-3108.
[59]
Kim, J.H.; Kang, J.W.; Kim, M.S.; Bak, Y.; Park, Y.S.; Jung, K.Y.; Lim, Y.H.; Yoon, D.Y. The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells. Toxicol. In Vitro, 2012, 26, 67-73.
[60]
Trisciuoglio, D.; Ragazzoni, Y.; Pelosi, A.; Desideri, M.; Carradori, S.; Gabellini, C.; Maresca, G.; Nescatelli, R.; Secci, D.; Bolasco, A.; Bizzarri, B.; Cavaliere, C.; D’Agnano, I.; Filetici, P.; Ricci-Vitiani, L.; Rizzo, M.G.; Del Bufalo, D. CPTH6, A thiazole derivative, induces histone hypoacetylation and apoptosis in human leukemia cells. Clin. Cancer Res., 2012, 18(2), 475-486.
[61]
Łazarenkow, A.; Nawrot-Modranka, J.; Brzezińska, E.; Krajewska, U.; Różalski, M. Synthesis, preliminary cytotoxicity evaluation of new 3-formylchromone hydrazones and phosphorohydrazone derivatives of coumarin and chromone. Med. Chem. Res., 2012, 21(8), 1861-1868.
[62]
Shi, Z.Y.; Li, Y.Q.; Kang, Y.H.; Hu, G.Q.; Huang-fu, C.S.; Deng, J.B.; Liu, B. Piperonal ciprofloxacin hydrazone induces growth arrest and apoptosis of human hepatocarcinoma SMMC-7721 cells. Acta Pharmacol. Sin., 2012, 33(2), 271-278.
[63]
Moktan, S.; Ryppa, C.; Kratz, F.; Raucher, D. A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis. Invest. New Drugs, 2012, 30, 236-248.
[64]
Despaigne, A.A.; Parrilha, G.L.; Izidoro, J.B.; da Costa, P.R.; dos Santos, R.G.; Piro, O.E.; Castellano, E.E.; Rocha, W.R.; Beraldo, H. 2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells. Eur. J. Med. Chem., 2012, 50, 163-172.
[65]
Sarıözkan, S.; Türk, G.; Çıkla-Süzgün, P.; Güvenç, M.; Yüce, A.; Yay, A.H.; Cantürk, F.; Küçükgüzel, Ş.G. Effect of etodolac hydrazone, a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity. Andrologia, 2016, 48(2), 177-188.
[66]
Zhang, Y.; Xiao, C.; Li, M.; Chen, J.; Ding, J.; He, C.; Zhuang, X.; Chen, X. Co-delivery of 10-hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy. Macromol. Biosci., 2013, 13(5), 584-594.
[67]
Sun, J.P.; Shi, Z.Y.; Liu, S.M.; Kang, Y.H.; Hu, G.Q.; Huangfu, C.S.; Deng, J.B.; Liu, B. Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells. Cancer Cell Int., 2013, 13, 67-77.
[68]
Sleebs, B.E.; Kersten, W.J.; Kulasegaram, S.; Nikolakopoulos, G.; Hatzis, E.; Moss, R.M.; Parisot, J.P.; Yang, H.; Czabotar, P.E.; Fairlie, W.D.; Lee, E.F.; Adams, J.M.; Chen, L.; van Delft, M.F.; Lowes, K.N.; Wei, A.; Huang, D.C.; Colman, P.M.; Street, I.P.; Baell, J.B.; Watson, K.; Lessene, G. Discovery of potent and selective benzothiazole hydrazone inhibitors of Bcl-XL. J. Med. Chem., 2013, 56(13), 5514-5540.
[69]
Nasr, T.; Bondock, S.; Youns, M. Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives. Eur. J. Med. Chem., 2014, 76, 539-548.
[70]
Kaplancıklı, Z.A.; Yurttaş, L.; Özdemir, A.; Turan-Zitouni, G.; Akalın Çiftçi, G.; Ulusoylar Yıldırım, Ş.; Abu Mohsen, U. Synthesis and antiproliferative activity of new 1,5-disubstituted tetrazoles bearing hydrazone moiety. Med. Chem. Res., 2014, 23, 1067-1075.
[71]
Carradori, S.; Rotili, D.; De Monte, C.; Lenoci, A.; D’Ascenzio, M.; Rodriguez, V.; Filetici, P.; Miceli, M.; Nebbioso, A.; Altucci, L.; Secci, D.; Mai, A. Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: enzyme and cellular studies. Eur. J. Med. Chem., 2014, 80, 569-578.
[72]
Küçükgüzel, Ş.G.; Koç, D.; Çıkla-Süzgün, P.; Özsavcı, D.; Bingöl-Özakpınar, Ö.; Mega-Tiber, P.; Orun, O.; Erzincan, P.; Sağ-Erdem, S.; Şahin, F. Synthesis of tolmetin hydrazide-hydrazones and discovery of a potent apoptosis ınducer in colon cancer cells. Arch. Pharm. (Weinheim), 2015, 348(10), 730-742.
[73]
Paterna, A.; Borralho, P.M.; Gomes, S.E.; Mulhovo, S.; Rodrigues, C.M.; Ferreira, M.J. Monoterpene indole alkaloid hydrazone derivatives with apoptosis inducing activity in human HCT116 colon and HepG2 liver carcinoma cells. Bioorg. Med. Chem. Lett., 2015, 25(17), 3556-3559.
[74]
Cui, J.; Liu, L.; Zhao, D.; Gan, C.; Huang, X.; Xiao, Q.; Qi, B.; Yang, L.; Huang, Y. Synthesis, characterization and antitumor activities of some steroidal derivatives with side chain of 17-hydrazone aromatic heterocycle. Steroids, 2015, 95, 32-38.
[75]
Zawawi, N.K.; Rajput, S.A.; Taha, M.; Ahmat, N.; Ismail, N.H.; Abdullah, N.; Khan, K.M.; Choudhary, M.I. Benzimidazole derivatives protect against cytokine-induced apoptosis in pancreatic β-Cells. Bioorg. Med. Chem. Lett., 2015, 25(20), 4672-4676.
[76]
Şenkardeş, S.; Kaushik-Basu, N.; Durmaz, İ.; Manvar, D.; Basu, A.; Atalay, R.; Küçükgüzel, Ş.G. Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors. Eur. J. Med. Chem., 2016, 108, 301-308.
[77]
Kamath, P.R.; Sunil, D.; Ajees, A.A.; Pai, K.S.; ′ Biswas, S.N -((2-(6-bromo-2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene)-benzohydrazide as a probable Bcl-2/Bcl-xL inhibitor with apoptotic and anti-metastatic potential. Eur. J. Med. Chem., 2016, 120, 134-147.
[78]
Das Mukherjee, D.; Kumar, N.M.; Tantak, M.P.; Das, A.; Ganguli, A.; Datta, S.; Kumar, D.; Chakrabarti, G. Development of novel bis(indolyl)-hydrazide-hydrazone derivatives as potent microtubule-targeting cytotoxic agents against A549 lung cancer cells. Biochemistry, 2016, 55(21), 3020-3035.
[79]
He, H.; Wang, X.; Shi, L.; Yin, W.; Yang, Z.; He, H.; Liang, Y. Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety. Bioorg. Med. Chem. Lett., 2016, 26(14), 3263-3270.
[80]
Živković, M.B.; Matić, I.Z.; Rodić, M.V.; Novaković, I.T.; Krivokuća, A.M.; Sladić, D.M.; Krstić, N.M. Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro. J. Steroid Biochem. Mol. Biol., 2017, 174, 72-85.
[81]
Li, Z.H.; Yang, D.X.; Geng, P.F.; Zhang, J.; Wei, H.M.; Hu, B.; Guo, Q.; Zhang, X.H.; Guo, W.G.; Zhao, B.; Yu, B.; Ma, L.Y.; Liu, H.M. Design, synthesis and biological evaluation of [1,2,3]triazolo[4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents. Eur. J. Med. Chem., 2016, 124, 967-980.
[82]
Gazieva, G.A.; Anikina, L.V.; Nechaeva, T.V.; Pukhov, S.A.; Karpova, T.B.; Popkov, S.V.; Nelyubina, Y.V.; Kolotyrkina, N.G.; Kravchenko, A.N. Synthesis and biological evaluation of new substituted thioglycolurils, their analogues and derivatives. Eur. J. Med. Chem., 2017, 140, 141-154.
[83]
Labib, M.B.; Philoppes, J.N.; Lamie, P.F.; Ahmed, E.R. Azole-hydrazone derivatives: Design, synthesis, in vitro biological evaluation, dual EGFR/HER2 inhibitory activity, cell cycle analysis and molecular docking study as anticancer agents. Bioorg. Chem., 2018, 76, 67-80.
[84]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[85]
Ulukaya, E.; Acilan, C.; Yilmaz, Y. Apoptosis: why and how does it occur in biology? Cell Biochem. Funct., 2011, 29(6), 468-480.
[86]
Millimouno, F.M.; Dong, J.; Yang, L.; Li, J.; Li, X. Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature. Cancer Prev. Res. (Phila.), 2014, 7(11), 1081-1107.
[87]
Obiorah, I.E.; Fan, P.; Sengupta, S.; Jordan, V.C. Selective estrogen-induced apoptosis in breast cancer. Steroids, 2014, 90C, 60-70.
[88]
Gillies, L.A.; Kuwana, T. Apoptosis regulation at the mitochondrial outer membrane. J. Cell. Biochem., 2014, 115(4), 632-640.
[89]
Kamal, A.; Faazil, S.; Malik, M.S. Apoptosis-inducing agents: A patent review (2010-2013). Expert Opin. Ther. Pat., 2014, 24(3), 339-354.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 17
Year: 2019
Published on: 24 September, 2019
Page: [1427 - 1442]
Pages: 16
DOI: 10.2174/1389557519666190410125910
Price: $65

Article Metrics

PDF: 34
HTML: 5