Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Novel bis-amide-based bis-thiazoles as Anti-colorectal Cancer Agents Through Bcl-2 Inhibition: Synthesis, In Vitro, and In Vivo studies

Author(s): Kamal M. Dawood*, Mohamed A. Raslan, Ashraf A. Abbas, Belal E. Mohamed and Mohamed S. Nafie

Volume 23, Issue 3, 2023

Published on: 22 August, 2022

Page: [328 - 345] Pages: 18

DOI: 10.2174/1871520622666220615140239

Price: $65

conference banner
Abstract

Background: Some heterocycles having bisamide linkage are receiving much interest due to their remarkable biological potencies and they are naturally occurring. Some bisamides and thiazole derivatives were found to inhibit the protein levels of Bcl-2 significantly. This prompted us to synthesize new bis(heterocyclic) derivatives having bisamide function to explore their anti-cancer activities.

Methods: Novel bis-amide-based bis-thiazoles and thiadiazoles were synthesized by reaction of a new bisthiosemicarbazone with a variety of hydrazonoyl chlorides, a-chloroacetylacetone and haloacetic acid derivatives. Most of the synthesized derivatives were tested for colorectal (HCT-116) and breast (MCF-7) cell lines using the MTT assay, with the apoptotic investigation through flow cytometric and RT-PCR analyses.

Results: Some derivatives were found to be highly cytotoxic against HCT-116 cells with an IC50 range of (10.44-13.76 μM) compared to 5-fluorouracil (5-FU) (IC50 = 11.78 μM). One product significantly stimulated apoptotic colorectal cancer cell death by 27.24-fold (50.13% compared to control 1.84%) by arresting the cell cycle at the G2/M phase. The obtained results revealed that compound 7f was more cytotoxic against HCT-116 cells than 5-FU. Compound 7f remarkably enhanced apoptotic colorectal cancer cell death and upregulated the propapoptotic genes (P53, BAX and Capases-3,-8,-9) and downregulated the anti-apoptotic gene, B-cell lymphoma 2 (Bcl-2). In vivo study exhibited that 7f-treatment caused tumor inhibition ratio (TIR%) of 50.45% compared to 54.86% in the 5-FU treatment, with a significant reduction in tumor mass and volume. The anti-tumor activity of compound 7f was accompanied by ameliorated hematological and biochemical analyses, histopathological improvement in treated liver tissues, and the immunohistochemical staining revealed Bcl-2 inhibition in agreement with the in vitro results.

Conclusion: Compound 7f is an interesting candidate for further development as a chemotherapeutic anti-cancer agent.

Keywords: Bis-thiazoles, bis-thiadiazoles, bis-thiazolidinone, hydrazonoyl chlorides, Bcl-2 inhibition, in vivo.

« Previous Next »
Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics. CA Cancer J. Clin., 2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[2]
Ramesh, P.; Medema, J.P. BCL-2 family deregulation in colorectal cancer: Potential for BH3 mimetics in therapy. Apoptosis, 2020, 25(5-6), 305-320.
[http://dx.doi.org/10.1007/s10495-020-01601-9] [PMID: 32335811]
[3]
Ma, Q.; Ding, W.; Chen, Z.; Ma, Z. Bisamides and rhamnosides from mangrove actinomycete Streptomyces sp. SZ-A15. Nat. Prod. Res., 2018, 32(7), 761-766.
[http://dx.doi.org/10.1080/14786419.2017.1315578] [PMID: 28438038]
[4]
Li, B.; Chen, G.; Bai, J.; Jing, Y.K.; Pei, Y.H. A bisamide and four diketopiperazines from a marine-derived Streptomyces sp. J. Asian Nat. Prod. Res., 2011, 13(12), 1146-1150.
[http://dx.doi.org/10.1080/10286020.2011.617744] [PMID: 21985013]
[5]
Zhang, L.; Wang, L.H.; Yang, Y.F.; Yang, S.M.; Zhang, J.H.; Tan, C.H. Aglaianine, a new bisamide from Aglaia abbreviata. Nat. Prod. Res., 2011, 25(18), 1676-1679.
[http://dx.doi.org/10.1080/14786419.2010.511219] [PMID: 22011253]
[6]
Abdelfattah, M.S.; Toume, K.; Ahmed, F.; Sadhu, S.K.; Ishibashi, M. Cucullamide, a new putrescine bisamide from Amoora cucullata. Chem. Pharm. Bull. (Tokyo), 2010, 58(8), 1116-1118.
[http://dx.doi.org/10.1248/cpb.58.1116] [PMID: 20686272]
[7]
Pakhomova, V.A.; Nebolsin, V.E.; Pershina, V.O.; Krupin, A.V.; Sandrikina, A.L.; Pan, S.E.; Ermakova, N.N.; Vaizova, E.O.; Widera, D.; Grimm, W.D.; Kravtsov, Y.V.; Afanasiev, A.S.; Morozov, G.S.; Kubatiev, A.A.; Dygai, M.A.; Skurikhin, G.E. Antidiabetic effects of bisamide derivative of dicarboxylic acid in metabolic disorders. Int. J. Mol. Sci., 2020, 21(3), 991.
[http://dx.doi.org/10.3390/ijms21030991] [PMID: 32028560]
[8]
Han, J.; Lee, H.W.; Jin, Y.; Khadka, D.B.; Yang, S.; Li, X.; Kim, M.; Cho, W.J. Molecular design, synthesis, and biological evaluation of bisamide derivatives as cyclophilin A inhibitors for HCV treatment. Eur. J. Med. Chem., 2020, 188, 112031.
[http://dx.doi.org/10.1016/j.ejmech.2019.112031] [PMID: 31923861]
[9]
Yang, S.; Jyothi, K.R.; Lim, S.; Choi, T.G.; Kim, J.H.; Akter, S.; Jang, M.; Ahn, H.J.; Kim, H.Y.; Windisch, M.P.; Khadka, D.B.; Zhao, C.; Jin, Y.; Kang, I.; Ha, J.; Oh, B.C.; Kim, M.; Kim, S.S.; Cho, W.J. Structure-based discovery of novel cyclophilin-A inhibitors for the treatment of hepatitis C virus infections. J. Med. Chem., 2015, 58(24), 9546-9561.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01064] [PMID: 26613291]
[10]
Rezayan, A.H.; Hariri, S.; Azerang, P.; Ghavami, G.; Portugal, I.; Sardari, S. Synthesis of novel fluorene bisamide derivatives via Ugi reaction and evaluation their biological activity against Mycobacterium species. Iran. J. Pharm. Res., 2017, 16(2), 745-755.
[PMID: 29118816]
[11]
El-Gamal, M.I.; Abdel-Maksoud, M.S.; El-Din, M.M.G.; Yoo, K.H.; Baek, D.; Oh, C.H. Cell-based biological evaluation of a new bisamide FMS kinase inhibitor possessing pyrrolo[3,2-c]pyridine scaffold. Arch. Pharm. (Weinheim), 2014, 347(9), 635-641.
[http://dx.doi.org/10.1002/ardp.201400051] [PMID: 24942978]
[12]
Gajko-Galicka, A.; Bielawski, K.; Sredzinska, K.; Bielawska, A.; Gindzienski, A. Elongation factor 2 as a target for selective inhibition of protein synthesis in vitro by the novel aromatic bisamidine. Mol. Cell. Biochem., 2002, 233(1-2), 159-164.
[http://dx.doi.org/10.1023/A:1015548131930] [PMID: 12083371]
[13]
Delaet, N.G.L.; Montalban, A.G.; Larson, C.; Lum, C.; Pei, Y.; Sebo, L.; Urban, J.; Wang, Z.; Boman, E. Preparation of pyridinylcarbox-amide derivatives as cytokine inhibitors. PCT Int. Appl WO 2007056016,
[14]
Avakyan, A.P.; Gevorgyan, G.A.; Agababyan, A.G.; Tumadzhyan, A.E.; Paronikyan, R.G.; Panosyan, G.A. Synthesis and biological activity of substituted bis(thiophenyl)-alkanediamides. Pharm. Chem. J., 2005, 39(6), 308-310.
[http://dx.doi.org/10.1007/s11094-005-0140-x]
[15]
Singh, K.; Banerjee, S.; Patra, A.K. Photocytotoxic luminescent lanthanide complexes of DTPA-bisamide using quinoline as photosensitizer. RSC Advances, 2015, 5(130), 107503-107513.
[http://dx.doi.org/10.1039/C5RA24329G]
[16]
Liu, W.; Liu, A.; Liu, X.; Long, C.; Yu, H.; Xiang, J.; Lei, M.; Li, Z.; Zhang, Z.; Yan, Z. N-2,4-substituted phenyl bisamide compound, its preparation method and application in preparation drug with insecticidal and/or bactericidal biological activity Faming Zh. Shenq CN11084347, 2016.
[17]
Chen, Y.; Chen, Z.; Chi, H.; Han, X. Pesticide and fungicide composition and application thereof, Faming Zh. Shenq. CN10283663, 2016.
[18]
Wang, G.; Qin, G.; Li, W.; Hu, J.; Gao, C. Oil suspension agent of bisamide insecticides and its preparation method, Faming Zh. Shenq. CN10489547, 2015.
[19]
He, S.; Li, J.; Wan, H.; You, H.; Gao, Y.; Zhang, X.; Liao, X. Nano silica-grafted organic functional polymer bisamide insecticides slow-release agent and its preparation method. CN10192026, 2016.
[20]
Fan, Z.; Zong, G.; Li, Y.; Li, J.; Ji, X; Liu, C.; Li, F.; Zhu, Y.; Chen, L. Preparation of Bisamide compound containing 3,4-dichloroisothiazole useful as insecticide, miticide and microbicide, Faming Zh. CN10481616, 2013.
[21]
Zhang, J.; Xu, Q.; Shen, S.; Jin, S. Bisamide compounds as fungicides and nematicides and preparation thereof, Faming Zh. CN10846201, 2019.
[22]
Tachdjian, C.; Patron, A.P.; Bakir, F.; Averbuj, C.; Priest, C.; Adamski-Werner, S.L.; Chen, Q.; Darmohusodo, V.; Lebl-Rinnova, M.; Kimmich, R.D.A.; Tang, X.Q.; Shigemura, R. Bis-aromatic amides and their uses as sweet flavor modifiers, tastants and taste enhancers. WO2006138512, 2006.
[23]
Feng, J.; Sun, G.; Pei, F.; Liu, M. Comparison between Gd-DTPA and several bisamide derivatives as potential MRI contrast agents. Bioorg. Med. Chem., 2003, 11(15), 3359-3366.
[http://dx.doi.org/10.1016/S0968-0896(03)00263-3] [PMID: 12837545]
[24]
Wu, Y.Q.; Belyakov, S.; Choi, C.; Limburg, D.; Thomas, B.E., IV; Vaal, M.; Wei, L.; Wilkinson, D.E.; Holmes, A.; Fuller, M.; McCormick, J.; Connolly, M.; Moeller, T.; Steiner, J.; Hamilton, G.S. Synthesis and biological evaluation of non-peptidic cyclophilin ligands. J. Med. Chem., 2003, 46(7), 1112-1115.
[http://dx.doi.org/10.1021/jm020409u] [PMID: 12646018]
[25]
Ling, Y.; Wang, Z.; Zhu, H.; Wang, X.; Zhang, W.; Wang, X.; Chen, L.; Huang, Z.; Zhang, Y. Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents. Bioorg. Med. Chem., 2014, 22(1), 374-380.
[http://dx.doi.org/10.1016/j.bmc.2013.11.013] [PMID: 24300920]
[26]
Fletcher, S.; Drennen, B.J.; Conlon, I.L.; Lanning, M.E. Preparation of various azoles as dual inhibitors of the BCL-2 and Hdm2 families through co-mimicry of the BH3 and p53-alpha-helices. WO040511, 2019.
[27]
Anuradha; Patel, S.; Patle, R.; Parameswaran, P.; Jain, A.; Shard, A. Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents. Eur. J. Pharm. Sci., 2019, 134, 20-30.
[http://dx.doi.org/10.1016/j.ejps.2019.04.005] [PMID: 30965082]
[28]
Romagnoli, R.; Baraldi, P.G.; Salvador, M.K.; Camacho, M.E.; Preti, D.; Tabrizi, M.A.; Bassetto, M.; Brancale, A.; Hamel, E.; Bortolozzi, R.; Basso, G. Synthesis and biological evaluation of 2-substituted-4-(3`,4`,5`-trimethoxyphenyl)-5-arylthiazoles as anti-cancer agents. Bioorg. Med. Chem., 2012, 20, 7083-7094.
[http://dx.doi.org/10.1016/j.bmc.2012.10.001] [PMID: 23117171]
[29]
Fang, H.; Fu, H.; Yang, X.; Xu, W.; Yi, F. Preparation of 3,5-disubstituted rhodanine as anti-apoptosis protein B-cell lymphoma-2 (BCL-2) inhibitor useful in the treatment of related diseases. CN104557764, 2015.
[30]
Wan, Y.; Wu, S.; Xiao, G.; Liu, T.; Hou, X.; Chen, C.; Guan, P.; Yang, X.; Fang, H. Design, synthesis and preliminary bioactivity studies of 2-thioxo-4-thiazolidinone derivatives as Bcl-2 inhibitors. Bioorg. Med. Chem., 2015, 23(9), 1994-2003.
[http://dx.doi.org/10.1016/j.bmc.2015.03.024] [PMID: 25818766]
[31]
de Marigorta, E.M.; Santos, J.M.L.; Ochoa de Retana, A.M.; Vicario, J.; Palacios, F. Multicomponent reactions (MCRs): A useful access to the synthesis of benzo-fused γ-lactams. Beilstein J. Org. Chem., 2019, 15, 1065-1085.
[http://dx.doi.org/10.3762/bjoc.15.104] [PMID: 31164944]
[32]
Paprocki, D.; Madej, A.; Koszelewski, D.; Brodzka, A.; Ostaszewski, R. Multicomponent reactions accelerated by aqueous micelles. Front Chem., 2018, 6, 502-523.
[http://dx.doi.org/10.3389/fchem.2018.00502] [PMID: 30406083]
[33]
Zhi, S.; Ma, X.; Zhang, W. Consecutive multicomponent reactions for the synthesis of complex molecules. Org. Biomol. Chem., 2019, 17(33), 7632-7650.
[http://dx.doi.org/10.1039/C9OB00772E] [PMID: 31339143]
[34]
Dawood, K.M.; Eldebss, T.M.A.; El-Zahabi, H.S.; Yousef, M.H. Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives. Eur. J. Med. Chem., 2015, 102, 266-276.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.005] [PMID: 26291036]
[35]
Dawood, K.M.; Abu-Deif, H.K.A. Synthesis and antimicrobial evaluation of some new 1,2-bis-(2-(N-arylimino)-1,3-thiazolidin-3-yl)ethane derivatives. Chem. Pharm. Bull. (Tokyo), 2014, 62(5), 439-445.
[http://dx.doi.org/10.1248/cpb.c14-00031] [PMID: 24789926]
[36]
Dawood, K.M.; Eldebss, T.M.A.; El-Zahabi, H.S.; Yousef, M.H.; Metz, P. Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. Eur. J. Med. Chem., 2013, 70, 740-749.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.042] [PMID: 24231309]
[37]
Hegazi, B.; Mohamed, H.A.; Dawood, K.M.; Badria, F.A.R. Cytotoxicity and utility of 1-indanone in the synthesis of some new heterocycles. Chem. Pharm. Bull. (Tokyo), 2010, 58(4), 479-483.
[http://dx.doi.org/10.1248/cpb.58.479] [PMID: 20410628]
[38]
Dawood, K.M.; Raslan, M.A.; Abbas, A.A.; Mohamed, B.E.; Abdellattif, M.H.; Nafie, M.S.; Hassan, M.K. Novel bis-thiazole derivatives: Synthesis and potential cytotoxic activity through apoptosis with molecular docking approaches. Front Chem., 2021, 9, 694870.
[http://dx.doi.org/10.3389/fchem.2021.694870] [PMID: 34458233]
[39]
Dawood, K.M. Bis-Thiourea derivatives and their utility in synthesis of mono-, bis- and fused- heterocyclic systems. J. Heterocycl. Chem., 2019, 56, 1701-1721.
[http://dx.doi.org/10.1002/jhet.3540]
[40]
Dawood, K.M.; El-Deftar, M.M. Microwave-assisted synthesis of 2-substituted 4-Biarylyl-1,3-thiazoles by Carbon–Carbon cross-coupling in water. Synthesis, 2010, 6(6), 1030-1038.
[http://dx.doi.org/10.1055/s-0029-1218662]
[41]
Abdel-Wahab, B.F.; Mohamed, H.A.; Farahat, A.A.; Dawood, K.M. Synthetic accesses to Azolylthiazoles. Heterocycles, 2011, 83, 2731-2767.
[http://dx.doi.org/10.3987/REV-11-717]
[42]
Kassab, R.M.; Khalil, F.S.; Abbas, A.A. Synthesis and antimicrobial activities of some new bis (Schiff Bases) and their triazole-based lariat macrocycles. Polycycl. Aromat. Compd., 2020, 1-16.
[http://dx.doi.org/10.1080/10406638.2020.1852272]
[43]
Dieckmann, W.; Platz, O. Convenient synthesis of azolopyrimidine, azolotriazine, azinobenzimidazole and 1,3,4-thiadiazole derivatives. Chem. Ber., 1906, 38, 2989-2995.
[44]
Hegarty, A.F.; Cashman, M.P.; Scott, F.L. Synthesis of aliphatic hydrazonyl bromides and kinetics of their conversion into hydrazides. J. Chem. Soc., Perkin Trans. 2, 1972, II(10), 1381-1386.
[http://dx.doi.org/10.1039/p29720001381]
[45]
Eweiss, N.F.; Osman, A. Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles. J. Heterocycl. Chem., 1980, 17(8), 1713-1717.
[http://dx.doi.org/10.1002/jhet.5570170814]
[46]
Farag, A.M.; Algharib, M.S. Synthesis and reactions of C-(2-thenoyl)-N-arylformhydrazidoyl bromides. Org. Prep. Proced. Int., 1988, 20(5), 521-526.
[http://dx.doi.org/10.1080/00304948809356298]
[47]
Sawhney, S.N.; Singh, J. Benzothiazole derivatives, Synthesis of 2-(4-thiazolyl)-and 6-(4-thiazolyl)-benzothiazoles and their derivatives as potential anthelmintics. Indian J. Chem., 1970, 8, 882.
[48]
Ismail, N.A. Reactions with coumarin derivatives: Synthesis of several new coumarinopyrazoles, coumarinopyridines and coumarinyl azoles. Egypt. J. Pharm. Sci., 1991, 32, 685-693.
[49]
Abdelhamid, A.O.; Negm, A.M.; Abdeen, T.M.S. Reactions with hydroxamoyl halides: Synthesis of several isoxazole, imidazo[1,2‐a]pyridine, imidazo[1,2‐a]pyrimidine and benz-1,2,4‐triazine derivatives. Arch. Pharm. (Weinheim), 1988, 321(12), 913-951.
[http://dx.doi.org/10.1002/ardp.19883211217]
[50]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[51]
Tantawy, E.S.; Amer, A.M.; Mohamed, E.K.; Abd Alla, M.M.; Nafie, M.S. Synthesis, characterization of some pyrazine derivatives as anti-cancer agents: In vitro and in silico approaches. J. Mol. Struct., 2020, 1210, 128013.
[http://dx.doi.org/10.1016/j.molstruc.2020.128013]
[52]
Nafie, M.S.; Amer, A.M.; Mohamed, A.K.; Tantawy, E.S. Discovery of novel pyrazolo[3,4-b]pyridine scaffold-based derivatives as po-tential PIM-1 kinase inhibitors in breast cancer MCF-7 cells. Bioorg. Med. Chem., 2020, 28(24), 115828.
[http://dx.doi.org/10.1016/j.bmc.2020.115828] [PMID: 33166925]
[53]
Nafie, M.S.; Arafa, K.; Sedky, N.K.; Alakhdar, A.A.; Arafa, R.K. Triaryl dicationic DNA minor-groove binders with antioxidant activity display cytotoxicity and induce apoptosis in breast cancer. Chem. Biol. Interact., 2020, 324, 109087.
[http://dx.doi.org/10.1016/j.cbi.2020.109087] [PMID: 32294457]
[54]
Gad, E.M.; Nafie, M.S.; Eltamany, E.H.; Hammad, M.S.A.G.; Barakat, A.; Boraei, A.T.A. Discovery of new apoptosis-inducing agents for breast cancer based on ethyl 2-Amino-4,5,6,7-Tetra Hydrobenzo[b]thiophene-3-carboxylate: Synthesis, in vitro, and in vivo activity evaluation. Molecules, 2020, 25(11), 2523.
[http://dx.doi.org/10.3390/molecules25112523] [PMID: 32481682]
[55]
Youssef, E.; El-Moneim, M.A.; Fathalla, W.; Nafie, M.S. Design, synthesis and antiproliferative activity of new amine, amino acid and dipeptide-coupled benzamides as potential sigma-1 receptor. J. Iran. Chem. Soc., 2020, 17(10), 2515-2532.
[http://dx.doi.org/10.1007/s13738-020-01947-6]
[56]
Nafie, M.S.; Mahgoub, S.; Amer, A.M. Antimicrobial and antiproliferative activities of novel synthesized 6-(quinolin-2-ylthio) pyridine derivatives with molecular docking study as multi-targeted JAK2/STAT3 inhibitors. Chem. Biol. Drug Des., 2021, 97(3), 553-564.
[http://dx.doi.org/10.1111/cbdd.13791] [PMID: 32920942]
[57]
Lo, P.Y.; Lee, G.Y.; Zheng, J.H.; Huang, J.H.; Cho, E.C.; Lee, K.C. Intercalating pyrene with polypeptide as a novel self-assembly nano-carrier for colon cancer suppression in vitro and in vivo. Mater. Sci. Eng. C, 2020, 109, 110593.
[http://dx.doi.org/10.1016/j.msec.2019.110593] [PMID: 32228904]
[58]
Abdella, A.M.; Abdelmoniem, A.M.; Ibrahim, N.S.; El-Hallouty, S.M.; Abdelhamid, I.A.; Elwahy, A.H.M. Synthesis, cytotoxicity and molecular docking simulation of novel bis-1,4-dihydropyridines linked to aliphatic or arene core via amide or ester-amide linkages. Mini Rev. Med. Chem., 2020, 20(9), 801-816.
[http://dx.doi.org/10.2174/1389557519666190919160019] [PMID: 31538896]
[59]
Pistritto, G.; Trisciuoglio, D.; Ceci, C.; Garufi, A.; D’Orazi, G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY), 2016, 8(4), 603-619.
[http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]
[60]
Althagafi, I.; El-Metwaly, N.; Farghaly, T.A. New series of thiazole derivatives: Synthesis, structural elucidation, antimicrobial activity, molecular modeling and MOE docking. Molecules, 2019, 24(9), 1741.
[http://dx.doi.org/10.3390/molecules24091741] [PMID: 31060260]
[61]
Mohareb, R.M.; Abdallah, A.E.M.; Ahmed, E.A. Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile. Acta Pharm., 2017, 67(4), 495-510.
[http://dx.doi.org/10.1515/acph-2017-0040] [PMID: 29337677]
[62]
Yurttaş, L.; Demir, B.; Çiftçi, G.A. Some thiazole derivatives combined with different heterocycles: Cytotoxicity evaluation and apoptosis inducing studies. Anticancer. Agents Med. Chem., 2018, 18(8), 1115-1121.
[http://dx.doi.org/10.2174/1871520618666180328115314] [PMID: 29595114]
[63]
Koff, J.L.; Ramachandiran, S.; Bernal-Mizrachi, L. A time to kill: Targeting apoptosis in cancer. Int. J. Mol. Sci., 2015, 16(2), 2942-2955.
[http://dx.doi.org/10.3390/ijms16022942] [PMID: 25636036]
[64]
Baig, S.; Seevasant, I.; Mohamad, J.; Mukheem, A.; Huri, H.Z.; Kamarul, T. Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Cell Death Dis., 2016, 7(1), e2058-e2058.
[http://dx.doi.org/10.1038/cddis.2015.275] [PMID: 26775709]
[65]
Fulda, S. Therapeutic opportunities based on caspase modulation. Semin. Cell Dev. Biol., 2018, 82, 150-157.
[http://dx.doi.org/10.1016/j.semcdb.2017.12.008] [PMID: 29247787]

Rights & Permissions Print Cite
Article Metrics
5
© 2024 Bentham Science Publishers | Privacy Policy