287
Views
9
CrossRef citations to date
0
Altmetric
Research Article

Chemical profiling, cytotoxic activities through apoptosis induction in human fibrosarcoma and carcinoma cells, and molecular docking of some 1,2,3-triazole-isoxazoline hybrids using the eugenol as a precursors

, , ORCID Icon, , , , , , ORCID Icon & show all
Pages 2759-2771 | Received 27 Oct 2021, Accepted 29 Jan 2022, Published online: 17 Feb 2022

References

  • A., Oubella, Az, E., El Mansouri, M., Fawzi, A., Bimoussa, Y., Laamari, A., Auhmani, H., Morjani, A., Robert, A., Riahi, A., & Ait Itto, M. Y. (2021). Thiazolidinone-linked 1,2,3-triazoles with monoterpenic skeleton as new potential anticancer agents: Design, synthesis and molecular docking studies. Bioorganic Chemistry, 115, 105184. https://doi.org/10.1016/j.bioorg.2021.105184
  • Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E.-M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E. H., Rollinger, J. M., Schuster, D., Breuss, J. M., Bochkov, V., Mihovilovic, M. D., Kopp, B., Bauer, R., Dirsch, V. M., & Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33(8), 1582–1614. https://doi.org/10.1016/j.biotechadv.2015.08.001
  • Azeddine, E., Oubella, A., & Mehdi, A. (2020). Design, synthesis, biological evaluation and molecular docking of new 1,3,4-oxadiazolehomonucleosides and their double-headed analogs as antitumor agents, Bioorganic Chemistry, 104558. https://doi.org/10.1016/j.bioorg.2020.104558.
  • Bastos, J. F. A., Moreira, I. J. A., Ribeiro, T. P., Medeiros, I. A., Antoniolli, A. R., De Sousa, D. P., & Santos, M. R. V. (2010). Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats. Basic & Clinical Pharmacology & Toxicology, 106(4), 331–337. https://doi.org/10.1111/j.1742-7843.2009.00492.x
  • Bimoussa, A., Oubella, A., Hachim, M. E., Fawzi, M., Itto, M. Y. A., Mentre, O., Ketatni, E. M., Bahsis, L., Morjani, H., & Auhmani, A. (2021). New enaminone sesquiterpenic: TiCl4-catalyzed synthesis, spectral characterization, crystal structure, Hirshfeld surface analysis, DFT studies and cytotoxic activity. Journal of Molecular Structure, 1241, 130622. https://doi.org/10.1016/j.molstruc.2021.130622
  • Boudreau, M. W., Peh, J., & Hergenrother, P. J. (2019). Procaspase-3 overexpression in cancer: a paradoxical observation with therapeutic potential. ACS Chemical Biology, 14(11), 2335–2348. https://doi.org/10.1021/acschembio.9b00338.
  • Conradt, B. (2009). Genetic control of programmed cell death during animal development. Annual Review of Genetics, 43, 493–523. https://doi.org/10.1146/annurev.genet.42.110807.091533
  • Cragg, G. M., Newman, D. J. (2013). Natural products: A continuing source of novel drug leads. Biochim Biophys Acta, 6, 1830. https://doi.org/10.1016/j.bbagen.2013.02.008.
  • D. M., Martino, R., Sessa, M. R., Storino, M., Giuliano, S., Trombetti, R., Catapano, A. L., Bianco, P., Izzo, & M. Grosso. (2020). Transcriptional repressors of fetal globin genes as novel therapeutic targets in beta-thalassemia. IntechOpen. https://doi.org/10.5772/intechopen.90762.
  • de Morais, S. M., Vila-Nova, N. S., Bevilaqua, C. M. L., Rondon, F. C., Lobo, C. H., Moura, A. A. A. N., Sales, A. D., Rodrigues, A. P. R., Figuereido, J. R., Campello, C. C., Wilson, M. E., & Andrade, H. F. (2014). Thymol and eugenol derivatives as potential antileishmanial agents. Bioorganic & Medicinal Chemistry, 22(21), 6250–6255. https://doi.org/10.1016/j.bmc.2014.08.020
  • Dheer, D., Singh, V., & Shankar, R. (2017). Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorganic Chemistry, 71, 30–54. 10.1016/j.bioorg.2017.01.010
  • El Mansouri, A. E, Oubella, K., Dânoun, M., Ahmad, J., Neyts, D., Jochmans, R., Snoeck, G., Andrei, H., Morjani, M., Zahouily, H. B. & Lazrek, (2021). Discovery of novel furo[2,3‐d]pyrimidin‐2‐one–1,3,4‐oxadiazole hybrid derivatives as dual antiviral and anticancer agents that induce apoptosis, Archiv der Pharmazie, 2100146. https://doi.org/10.1002/ardp.202100146.
  • El Mansouri, A.-E., Oubella, A., Maatallah, M., Ait Itto, M. Y., Zahouily, M., Morjani, H., & Lazrek, H. B. (2020). Design, synthesis, biological evaluation and molecular docking of new uracil analogs-1,2,4-oxadiazole hybrids as potential anticancer agents. Bioorganic & Medicinal Chemistry Letters, 30(19), 127438. https://doi.org/10.1016/j.bmcl.2020.127438
  • Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495–516. https://doi.org/10.1080/01926230701320337
  • El-Sherief, H. A. M., Youssif, B. G. M., Abbas Bukhari, S. N., Abdelazeem, A. H., Abdel-Aziz, M., & Abdel-Rahman, H. M. (2018). Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors. European Journal of Medicinal Chemistry, 156, 774–789. https://doi.org/10.1016/j.ejmech.2018.07.024
  • Eswaran, S., Adhikari, A. V., & Shetty, N. S. (2009). Synthesis and antimicrobial activities of novel quinoline derivatives carrying 1,2,4-triazole moiety. European Journal of Medicinal Chemistry, 44(11), 4637–4647. https://doi.org/10.1016/j.ejmech.2009.06.031S0223-5234(09)00360-2
  • Fawzi, M., Laamari, Y., Koumya, Y., Oubella, A., Auhmani, A., Itto, M. Y. A., Abouelfida, A., Riahi, A., & Auhmani, A. (2021). Electrochemical and theoretical studies on the corrosion inhibition performance of some synthesized D-Limonene based heterocyclic compounds. Journal of Molecular Structure, 1244, 130957. https://doi.org/10.1016/j.molstruc.2021.130957
  • Fonsêca, D. V., Salgado, P. R. R., Aragão Neto, H. d C., Golzio, A. M. F. O., Caldas Filho, M. R. D., Melo, C. G. F., Leite, F. C., Piuvezam, M. R., Pordeus, L. C. d M., Barbosa Filho, J. M., & Almeida, R. N. (2016). Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities. International Immunopharmacology, 38, 402–408. https://doi.org/10.1016/j.intimp.2016.06.005
  • Francisco, F. M. S., Francisco, J. Q. M., Telma, L. G. L., Patrícia, G. G. N., Alana, K. M. C., & Luanda, M. M. P. (2018). Eugenol derivatives: Synthesis, characterization, and evaluation of antibacterial and antioxidant activities. Chemistry Central Journal, 12(34). https://doi.org/10.1186/s13065-018-0407-4.
  • Hachim, M. E., Oubella, A., & Byadi, S. (2021). Newly synthesized (R)-carvone-derived 1, 2, 3-triazoles: Structural, mechanistic, cytotoxic and molecular docking studies, Journal of Biomolecular Structure and Dynamics, 1–14. https://doi.org/10.1080/07391102.2021.1894984.
  • Hachim, M. E., Oubella, A., Byadi, S., Fawzi, M., Laamari, Y., Bahsis, L., Aboulmouhajir, A., Morjani, H., Podlipnik, Č., Auhmani, A., & Ait Itto, M. Y. (2021). 1,2,3-Triazoles: Structural, mechanistic, cytotoxic and molecular docking studies. Journal of Biomolecular Structure and Dynamics, 1–14. https://doi.org/10.1080/07391102.2021.1894984
  • Husain, A., Rashid, M., Shaharyar, M., Siddiqui, A. A., Mishra, R. (2013). Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: New anticancer agents. European Journal of Medicinal Chemistry, 62, 785–798. https://doi.org/10.1016/j.ejmech.2012.07.011
  • Hyang, N., & Moon-Moo, K. (2013). Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells. Food and Chemical Toxicology, 55, 106–112. https://doi.org/10.1016/j.fct.2012.12.050.
  • Jadhav, R. D., Kadam, K. S., Kandre, S., Guha, T., Reddy, M. M. K., Brahma, M. K., Deshmukh, N. J., Dixit, A., Doshi, L., Potdar, N., Enose, A. A., Vishwakarma, R. A., Sivaramakrishnan, H., Srinivasan, S., Nemmani, K. V. S., Gupte, A., Gangopadhyay, A. K., & Sharma, R. (2012). Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors. European Journal of Medicinal Chemistry, 54, 324–342. https://doi.org/10.1016/j.ejmech.2012.05.016
  • Jensen, M. R., Schoepfer, J., Radimerski, T., Massey, A., Guy, C. T., Brueggen, J., Quadt, C., Buckler, A., Cozens, R., Drysdale, M. J., Garcia-Echeverria, C., & Chène, P. (2008). NVP-AUY922: A small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Research: BCR, 10(2), R33. https://doi.org/10.1186/bcr1996.
  • Jiang, X., Kim, H.-E., Shu, H., Zhao, Y., Zhang, H., Kofron, J., Donnelly, J., Burns, D., Ng, S-c., Rosenberg, S., & Wang, X. (2003). Distinctive roles of PHAP proteins and prothymosin-α in a death regulatory pathway. Science, 299(5604), 223–226. https://doi.org/10.1126/science.1076807
  • Kamal, A., Surend, R. J., Janaki, R. M., Dastagiri, D., Vijaya, B. E., Ameruddin, A. M., Sultana, F., Pushpavalli, S. N. C. V. L., Pal-Bhadra, M., Juvekar, A., Sen, S., Zingde, S., & Juvekar, A. (2010). Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents. European Journal of Medicinal Chemistry, 45(9), 3924–3937. https://doi.org/10.1016/j.ejmech.2010.05.047
  • Kankala, S., Kankala, R. K., Gundepaka, P., Thota, N., Nerella, S., Gangula, M. R., Guguloth, H., Kagga, M., Vadde, R., & Vasam, C. S. (2013). Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their in vivo analgesic and anti-inflammatory activity studies. Bioorganic & Medicinal Chemistry Letters, 23(5), 1306–1309. https://doi.org/10.1016/j.bmcl.2012.12.101
  • Kaufman, T. S. J. (2015). The multiple faces of eugenol. A versatile starting material and building block for organic and bio-organic synthesis and a convenient precursor toward bio-based fine chemicals, Journal of the Brazilian Chemical Society, 26(6), 1055–1085. https://doi.org/10.5935/0103-5053.20150086.
  • Kesornpun, C., Aree, T., Mahidol, C., Ruchirawat, S., & Kittakoop, P. (2016). Water-assisted nitrile oxide cycloadditions: Synthesis of isoxazoles and stereoselective syntheses of isoxazolines and 1,2,4-oxadiazoles. Angewandte Chemie (International ed. in English), 55(12), 3997–4001. https://doi.org/10.1002/anie.201511730
  • Kodama, T., Ito, T., Dibwe, D. F., Woo, S.-Y., & Morita, H. (2017). Syntheses of benzophenone-xanthone hybrid polyketides and their antibacterial activities. Bioorganic & Medicinal Chemistry Letters, 27(11), 2397–2400. https://doi.org/10.1016/j.bmcl.2017.04.017
  • Kónya, B., Docsa, T., Gergely, P., & Somsák, L. (2012). Synthesis of heterocyclic N-(β-D-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase. Carbohydrate Research, 351, 56–63. https://doi.org/10.1016/j.carres.2012.01.020
  • Kordali, S., Kotan, R., Mavi, A., Cakir, A., Ala, A., & Yildirim, A. (2005). Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. Journal of Agricultural and Food Chemistry, 53(24), 9452–9458. https://doi.org/10.1021/jf0516538
  • Kucukguzel, I., Tatar, E., Kucukguzel, S. G., Rollas, S., & De Clercq, E. (2008). Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and antituberculosis agents. European Journal of Medicinal Chemistry, 43(2), 381–392. https://doi.org/10.1016/j.ejmech.2007.04.010
  • Kumbhare, R. M., Kosurkar, U. B., Janaki Ramaiah, M., Dadmal, T. L., Pushpavalli, S. N. C. V. L., & Pal-Bhadra, M. (2012). Synthesis and biological evaluation of novel triazoles and isoxazoles linked 2-phenyl benzothiazole as potential anticancer agents. Bioorganic & Medicinal Chemistry Letters, 22(17), 5424–5427. https://doi.org/10.1016/j.bmcl.2015.09.003.
  • Laamari, Y., Oubella, A., Bimoussa, A., El Mansouri, A.-E., Ketatni, E. M., Mentre, O., Ait Itto, M. Y., Morjani, H., Khouili, M., & Auhmani, A. (2021). Design, hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol. Bioorganic Chemistry, 115, 105165. https://doi.org/10.1016/j.bioorg.2021.105165
  • Leung, D., Abbenante, G., & Fairlie, D. P. (2000). Protease inhibitors: Current status and future prospects. Journal of Medicinal Chemistry, 43(3), 305–341. https://doi.org/10.1021/jm990412m
  • Lobanov, M. Y., Bogatyreva, N. S., & Galzitskaya, O. V. (2008). Radius of gyration as an indicator of protein structure compactness. Molecular Biology, 42(4), 623–628. https://doi.org/10.1134/S0026893308040195
  • Martínez, L. (2015). Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS One, 10(3), e0119264–10. https://doi.org/10.1371/journal.pone.0119264
  • Melhado, L. L., & Leonard, N. J. (1983). An efficient synthesis of azidoindoles and azidotryptophans. The Journal of Organic Chemistry, 48(25), 5130–5133. https://doi.org/10.1021/jo00173a071
  • Moussaoui, O., Byadi, S., Eddine Hachim, M., Sghyar, R., Bahsis, L., Moslova, K., Aboulmouhajir, A., Rodi, Y. K., Podlipnik, Č., Hadrami, E. M. E., & Chakroune, S. (2021). Selective synthesis of novel quinolones-amino esters as potential antibacterial and antifungal agents: Experimental, mechanistic study, docking and molecular dynamic simulations. Journal of Molecular Structure., 1241, 130652. https://doi.org/10.1016/j.molstruc.2021.130652
  • Oubella, A., Ait Itto, M. Y., Auhmani, A., Riahi, A., Daran, J.-C., & Auhmani, A. (2020). Crystal structure of (R)-5-[(R)-3-(4-chloro-phen-yl)-5-methyl-4,5-di-hydro-isoxazol-5-yl]-2-methyl-cyclo-hex-2-enone. Acta Crystallographica E Crystallographic Communications, 76(Pt 3), 400–403. https://doi.org/10.1107/S2056989020001991
  • Oubella, A., Ait Itto, M. Y., Auhmani, A., Riahi, A., Robert, A., Daran, J.-C., Morjani, H., Parish, C. A., & Esseffar, M. (2019). Diastereoselective synthesis and cytotoxic evaluation of new isoxazoles and pyrazoles with monoterpenic skeleton. Journal of Molecular Structure, 1198, 126924. https://doi.org/10.1016/j.molstruc.2019.126924
  • Oubella, A., Fawzi, M., Auhmani, A., Riahi, A., Morjani, H., Robert, A., & Ait Itto, M. Y. (2020). Synthesis and antitumor activity of novel heterocyclic systems with monoterpenic skeleton combining. ChemistrySelect, 5(21), 6403–6406. https://doi.org/10.1002/slct.202001284
  • Paprocka, R., Wiese, M., Eljaszewicz, A., Helmin-Basa, A., Gzella, A., Modzelewska-Banachiewicz, B., & Michalkiewicz, J. (2015). Synthesis and anti-inflammatory activity of new 1,2,4-triazole derivatives. Bioorganic & Medicinal Chemistry Letters, 25(13), 2664–2667. https://doi.org/10.1016/j.bmcl.2015.04.079
  • Patra, A. K., & Saxena, J. (2010). A new perspective on the use of plant secondary metabolites to inhibit methanogenesis in the rumen. Phytochemistry, 71(11–12), 1198–1222. https://doi.org/10.1016/j.phytochem.2010.05.010
  • Pinto, N. F. S., Pereira, D. M., Pereira, R. B., Fortes, A. G., Fernandes, M. J. G., Castanheira, E. M. S., & Gonçalves, M. S. T. (2020). Synthesis of amino alcohols from eugenol and their insecticidal activity against Sf9 cell line. Chemistry Proceedings, 3(1), 62. https://doi.org/10.3390/ecsoc-24-08337
  • Pokuri, S., Singla, R. K., Bhat, V. G., & Shenoy, G. G. (2014). Insights on the antioxidant potential of 1, 2, 4-triazoles: Synthesis, screening & QSAR studies. Current Drug Metabolism, 15(4), 389–397. 10.2174/1389200215666140908101958
  • Ríos-Gutiérrez, M., Domingo, L. R., Esseffar, M., Oubella, A., & Ait Itto, M. Y. (2020). Unveiling the different chemical reactivity of diphenyl nitrilimine and phenyl nitrile oxide in [3 + 2] cycloaddition reactions with (R)-carvone through the molecular electron density theory. Molecules, 25(5), 1085–1016. https://doi.org/10.3390/molecules25051085
  • Shi, L., Hu, R., Wei, Y., Liang, Y., Yang, Z., & Ke, S. (2012). Anthranilic acid-based diamides derivatives incorporating aryl-isoxazoline pharmacophore as potential anticancer agents: Design, synthesis and biological evaluation. European Journal of Medicinal Chemistry, 54, 549–556. https://doi.org/10.1016/j.ejmech.2012.06.001
  • Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 69(1), 7–34. https://doi.org/10.3322/caac.21551
  • Simoni, D., Grisolia, G., Giannini, G., Roberti, M., Rondanin, R., Piccagli, L., Baruchello, R., Rossi, M., Romagnoli, R., Invidiata, F. P., Grimaudo, S., Jung, M. K., Hamel, E., Gebbia, N., Crosta, L., Abbadessa, V., Di Cristina, A., Dusonchet, L., Meli, M., & Tolomeo, M. (2005). Heterocyclic and phenyl double-bond-locked combretastatin analogues possessing potent apoptosis-inducing activity in HL60 and in MDR cell lines. Journal of Medicinal Chemistry, 48(3), 723–736. https://doi.org/10.1021/jm049622b
  • Sun, W.-J., Lv, W.-J., Li, L.-N., Yin, G., Hang, X., Xue, Y., Chen, J., & Shi, Z. (2016). Eugenol confers resistance to tomato yellow leaf curl virus (TYLCV) by regulating the expression of SlPer1 in tomato plants. New Biotechnology, 33(3), 345–354. https://doi.org/10.1016/j.nbt.2016.01.001
  • Taia, A., ElIbrahimi, B., Benhiba, F., Ashfaq, M., Tahir, M. N., Essaber, M., Aatif, A., Hökelek, T., Mague, J. T., Sebbar, N. K., Essassi, E. M., & Acta, C. E. (2021). Syntheses, single crystal x-ray structure, Hirshfeld surface analyses, DFT computations and Monte Carlo simulations of new eugenol derivatives bearing 1,2,3-triazole moiety. Journal of Molecular Structure, 1234, 130189. https://doi.org/10.1016/j.molstruc.2021.130189
  • Taia, A., Essaber, M., Oubella, A., Aatif, A., Bodiguel, J., & Jamart-Grégoire, B., Ait Itto, M. Y., & Morjani, H. (2020). Synthesis, characterization, and biological evaluation of new heterocyclic systems 1, 2, 3-triazole-isoxazoline from eugenol by the mixed condensation reactions. Synthetic Communications, https://doi.org/10.1080/00397911.2020.1762224.
  • Tietze, L. F., Bell, H. P., & Chandrasekhar, S. (2003). Natural product hybrids as new leads for drug discovery. Angewandte Chemie (International ed. in English), 42(34), 3996–4028. https://doi.org/10.1002/anie.200200553
  • Timur, I., Kocyigit, U. M., Dastan, T., Sandal, S., Ceribasi, A. O., & P. J. Biochem, T. (2018). In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones – Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles, Molecular Toxicology, e22239. https://doi.org/10.1002/jbt.22239.
  • Touré, B. B., Miller-Moslin, K., Yusuff, N., Perez, L., Doré, M., Joud, C., Michael, W., DiPietro, L., van der Plas, S., McEwan, M., Lenoir, F., Hoe, M., Karki, R., Springer, C., Sullivan, J., Levine, K., Fiorilla, C., Xie, X., Kulathila, R., … Visser, M. (2013). The role of the acidity of N-heteroaryl sulfonamides as inhibitors of Bcl-2 family protein–protein interactions. ACS Medicinal Chemistry Letters, 4(2), 186–190. https://doi.org/10.1021/ml300321d
  • Villoutreix, B. O., Renault, N., Lagorce, D., Sperandio, O., Montes, M., & Miteva, M. A. (2007). Free resources to assist structure-based virtual ligand screening experiments. Current Protein & Peptide Science, 8(4), 381–411. https://doi.org/10.2174/138920307781369391
  • Wendel, T., Zhen, Y., Suo, Z., Bruheim, S., Wiedlocha, A., & Suo, Z. (2016). The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo. Experimental Cell Research, 340(2), 220–226. https://doi.org/10.1016/j.yexcr.2015.12.017
  • Wong, R. J. (2011). Apoptosis in cancer: from pathogenesis to treatment. Clinical Cancer Research, 30(87). https://doi.org/10.1186/1756-9966-30-87.
  • Yu, L. F., Eaton, J. B., Fedolak, A., Zhang, H.-K., Hanania, T., Brunner, D., Lukas, R. J., & Kozikowski, A. P. (2012). Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II . Journal of Medicinal Chemistry, 55(22), 9998–10009. Epub 2012 Nov 2. https://doi.org/10.1021/jm301177j
  • Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The traditional medicine and modern medicine from natural products. Molecules, 21(5), 559–518. https://doi.org/10.3390/molecules21050559
  • Zimmermann, K. C., & Green, D. R. (2001). How cells die: Apoptosis pathways. The Journal of Allergy and Clinical Immunology, 108, 99–103. https://doi.org/10.1067/mai.2001.117819.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.