Novel therapeutic compound acridine–retrotuftsin action on biological forms of melanoma and neuroblastoma - Publication - Bridge of Knowledge

Your account

login

Search

Novel therapeutic compound acridine–retrotuftsin action on biological forms of melanoma and neuroblastoma

Abstract

PURPOSE: As a continuation of our search for anticancer agents, we have synthesized a new acridine-retrotuftsin analog HClx9-[Arg(NO2)-Pro-Lys-Thr-OCH3]-1-nitroacridine (named ART) and have evaluated its activity against melanoma and neuroblastoma lines. Both tumors develop from cells (melanocytes, neurons) of neuroectodermal origin, and both are tumors with high heterogeneity and unsatisfactory susceptibility to chemotherapies. Thus, we analyzed the action of ART on pairs of biological forms of melanoma (amelanotic and melanotic) and neuroblastoma (dopaminergic and cholinergic) with regard to proliferation, mechanism of cell death, and effect on the activity of tricarboxylic acid cycle (TAC) enzymes. METHODS: The cytotoxicity of ART was evaluated by XTT and trypan blue tests. Cell death was estimated by plasma membrane structure changes (phosphatidylserine and calreticulin externalization), caspase activation, presence of ROS (reactive oxygen species), activity of tricarboxylic acid cycle enzymes (pyruvate dehydrogenase complex, aconitase, and isocitrate dehydrogenase), NAD level, and ATP level. RESULTS: ART influences the biological forms of melanoma and neuroblastoma in different ways. Amelanotic (Ab) melanoma (with the inhibited melanogenesis, higher malignancy) and SHSY5Y neuroblastoma (with cholinergic DC cells) were especially sensitive to ART action. The Ab melanoma cells died through apoptosis, while, with SH-SY5Y-DC neuroblastoma, the number of cells decreased but not as a result of apoptosis. With Ab melanoma and SH-SY5Y-DC cells, a diminished activity of TAC enzymes was noticed, along with ATP/NAD depletion. CONCLUSION: Our data show that the biological forms of certain tumors responded in different ways to the action of ART. As a combination of retrotuftsin and acridine, the compound can be an inducer of apoptotic cell death of melanoma, especially the amelanotic form. Although the mechanism of the interrelationships between energy metabolism and cell death is not fully understood, interference of ART with TAC enzymes could encourage the further investigation of its anticancer action.

Citations

  • 4

    CrossRef

  • 0

    Web of Science

  • 4

    Scopus

Authors (6)

Cite as

Full text

download paper
downloaded 26 times
Publication version
Accepted or Published Version
License
Creative Commons: CC-BY open in new tab

Keywords

Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY no. 145, pages 165 - 179,
ISSN: 0171-5216
Language:
English
Publication year:
2019
Bibliographic description:
Cichorek M., Ronowska A., Gensicka-Kowalewska M., Deptula M., Pelikant-Malecka I., Dzierzbicka K.: Novel therapeutic compound acridine–retrotuftsin action on biological forms of melanoma and neuroblastoma// JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY -Vol. 145,iss. 1 (2019), s.165-179
DOI:
Digital Object Identifier (open in new tab) 10.1007/s00432-018-2776-4
Bibliography: test
  1. Abbas S, Lugthart S, Kavelaars FG, Schelen A, Koenders JE, Zeile- maker A, van Putten WJ, Rijneveld AW, Löwenberg B, Valk PJ (2010) Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: preva- lence and prognostic value. Blood 116:2122-2126 open in new tab
  2. An Y, Li L, Yang D, Jia N, Xu C, Wang Q, Wang S, Yuan S (2014) Anticancer activity of tuftsin-derived T peptide in postopera- tive residual tumors. Anticancer Drugs 25:857-867. https ://doi. org/10.1097/CAD.00000 00000 00011 1 open in new tab
  3. Antonini I (2002) DNA-binding antitumor agents: from pyrimido[5,6,1- de/acridines to other intriguing classes of acridine derivatives. Curr Med Chem 9:1701-1716 open in new tab
  4. Bielarczyk H, Jankowska A, Madziar B, Matecki A, Michno A, Szu- towicz A (2003) Differential toxicity of nitric oxide, aluminum, and amyloid beta-peptide in SN56 cholinergic cells from mouse septum. Neurochem Int 42:323-331 open in new tab
  5. Blusztajn JK, Liscovitch M, Richardson UI (1987) Synthesis of ace- tylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. Proc Natl Acad Sci USA 84:5474-5477 open in new tab
  6. Boeckmann L, Nickel AC, Kuschal C, Schaefer A, Thoms KM, Schön MP, Thomale J, Emmert S (2011) Temozolomide chemoresist- ance heterogeneity in melanoma with different treatment regi- mens: DNA damage accumulation contribution. Melanoma Res 21:206-216. https ://doi.org/10.1097/CMR.0b013 e3283 45af9 5 open in new tab
  7. Bomirski A, Slomiński A, Bigda J (1988) The natural history of a fam- ily of transplantable melanomas in hamsters. Cancer Metastasis Rev 7:95-118 open in new tab
  8. Castillo-González D, Cabrera-Pérez MA, Pérez-González M, Morales Helguera A, Durán-Martínez A (2009) Prediction of telomerase inhibitory activity for acridinic derivatives based on chemical structure. Eur J Med Chem Eur 44:4826-4840 open in new tab
  9. Cen J, Guo H, Hong C, Lv J, Yang Y, Wang T, Fang D, Luo W, Wang C (2018) Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity. Eur J Med Chem 144:128-136 open in new tab
  10. Chakrabarti L, Abou-Antoun T, Vukmanovic S, Sandler AD (2012) Reversible adaptive plasticity: a mechanism for neuroblastoma cell heterogeneity and chemo-resistance. Front Oncol 2:82. https ://doi.org/10.3389/fonc.2012.00082 open in new tab
  11. Chen KG, Leapman RD, Zhang G, Lai B, Valencia JC, Cardarelli CO, Vieira WD, Hearing VJ, Gottesman MM (2009) Influence of melanosome dynamics on melanoma drug sensitivity. J Natl Cancer Inst 101:1259-1271. https ://doi.org/10.1093/jnci/djp25 9 open in new tab
  12. Cholewinski G, Iwaszkiewicz-Grzes D, Trzonkowski P, Dzierzbicka K (2016) Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immuno- suppressive agents. J Enzym Inhib Med Chem 31:974-982 open in new tab
  13. Cichorek M (2011) Camptothecin-induced death of amelanotic and melanotic melanoma cells in different phases of cell cycle. Neo- plasma 58:227-234 open in new tab
  14. Dang L, Yen K, Attar EC (2016) IDH mutations in cancer and pro- gress toward development of targeted therapeutics. Ann Oncol 27:599-608. https ://doi.org/10.1093/annon c/mdw01 3 open in new tab
  15. De Ferrari GV, von Bernhardi R, Calderón FH, Luza SC, Inestrosa NC (1998) Responses induced by tacrine in neuronal and non- neuronal cell lines. J Neurosci Res 52:435-444 open in new tab
  16. Denny WA (2004) Chemotherapeutic effects of acridine derivatives. Med Chem 1:257-266 open in new tab
  17. Dudek-Perić AM, Ferreira GB, Muchowicz A, Wouters J, Prada N, Martin S, Kiviluoto S, Winiarska M, Boon L, Mathieu C, van den Oord J, Stas M, Gougeon ML, Golab J, Garg AD, Agostinis P (2015) Antitumor immunity triggered by melphalan is potenti- ated by melanoma cell surface-associated calreticulin. Cancer Res 75:1603-1614. https ://doi.org/10.1158/0008-5472.CAN-14-2089 open in new tab
  18. Dzierzbicka K (2008) Synthesis of new conjugates of MPD and nor- MDP with retro-tuftsin derivatives as potential immunomodula- tors. Polish J Chem 82:1431-1439
  19. Dzierzbicka K, Kołodziejczyk AM, Wysocka-Skrzela B, Myśliwski A, Sosnowska D (2001) Synthesis and antitumor activity of con- jugates of muramyldipeptide, normuramyl dipeptide, and desmu- ramylpeptides with acridine/acridone derivatives. J Med Chem 44:3606-3615 open in new tab
  20. Ferguson LR, Denny WA (1991) The genetic toxicology of acridines. Mutat Res 258:123-160 open in new tab
  21. Forschner A, Eichner F, Amaral T, Keim U, Garbe C, Eigentler TK (2017) Improvement of overall survival in stage IV melanoma patients during 2011-2014: analysis of real-world data in 441 patients of the German Central Malignant Melanoma Registry (CMMR). J Cancer Res Clin Oncol 2017 143:533-540. https :// doi.org/10.1007/s0043 2-016-2309-y open in new tab
  22. Fridkin M, Najjar VA (1989) Tuftsin: its chemistry, biology, and clini- cal potential. Crit Rev Biochem Mol Biol 24:1-40 open in new tab
  23. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486-541. https ://doi.org/10.1038/s4141 8-017-0012-4 open in new tab
  24. Gensicka-Kowalewska M, Cholewiński G, Dzierzbicka K (2017) Recent developments in the synthesis and biological activity of acridine/acridone analogues. RSC Adv 7:15776-15804 open in new tab
  25. Gensicka-Kowalewska M, Cichorek M, Ronowska A, Deptula M, Kle- jbor I, Dzierzbicka K (2018) Synthesis and biological evaluation of acridine/acridone analogs as potential anticancer agents. Med Chem. https ://doi.org/10.2174/15734 06414 66618 10151 45120 open in new tab
  26. Gunaratnam M, Greciano O, Martins C, Reszka AP, Schultes CM, Morjani H, Riou JF, Neidle S (2007) Mechanism of acridine- based telomerase inhibition and telomere shortening. Biochem Pharmacol 74:679-689 open in new tab
  27. Januchta W, Serocki M, Dzierzbicka K, Cholewinski G, Skladanowski A (2015) Synthesis of functionalized new conjugates of batracylin with tuftsin/retro-tuftsin derivatives and their biological evalua- tion. Eur J Med Chem 106:85-94 open in new tab
  28. Kang MR, Kim MS, Oh JE et al (2009) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Can- cer 125:353-355 open in new tab
  29. Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M, Sukkurwala AQ, Menger L, Zitvogel L, Kroemer G (2011) Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 30:61-99. https ://doi.org/10.1007/s1055 5-011-9273-4 open in new tab
  30. King A, Selak MA, Gottlieb E (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25:4675-4682 open in new tab
  31. Kitchen SE, Wang YH, Baumstark AL, Wilson WD, Boykin DW (1985) The intercalation of 6-chloro-substituted-9-[[3- (dimethylamino)propyl]amino]acridines with DNA. J Med Chem 28:940-944 open in new tab
  32. Kroemer G, Pouyssegur J (2008) Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 13:472-482 open in new tab
  33. Kukowska M (2017) Amino acid or peptide conjugates of acridine/ acridone and quinoline/quinolone-containing drugs. A critical examination of their clinical effectiveness within a twenty-year timeframe in antitumor chemotherapy and treatment of infectious diseases. Eur J Pharm Sci 109:587-615 open in new tab
  34. Kukowska-Kaszuba M, Dzierzbicka K (2007) Synthesis and structure- activity studies of peptide-acridine/acridone conjugates. Curr Med Chem 14:3079-3104 open in new tab
  35. Larsson BS (1993) Interaction between chemicals and melanin. Pig- ment Cell Res 6:127-133 open in new tab
  36. Ledochowski A (1976) Ledacrin-anticancerous medicine 1-nitro- 9(3-dimethyloamino-propylamino)-acridine-2HCl-H 2 O. Mater Med Pol 8:237-251
  37. Leopold WR, Corbett TH, Griswold DP, Plowman J, Baguley BC (1987) Experimental antitumor activity of the amsacrine analogue CI-9211. J Natl Cancer Inst 79:343-349 open in new tab
  38. Lopez GY, Reitman ZJ, Solomon D, Waldman T, Bigner DD, McLen- don RE, Rosenberg SA, Samuels Y, Yan HLopez GY, Reitman ZJ, Solomon D, Waldman T, Bigner DD, McLendon RE, Rosenberg SA, Samuels Y, Yan H (2010) IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metas- tases to the brain. Biochem Biophys Res Commun 398:585-587. https ://doi.org/10.1016/j.bbrc.2010.06.125 (Epub 2010 Jul 13) open in new tab
  39. Lu X, Zhang Q, Wang Y, Zhang L, Zhao H, Chen C, Wang Y, Liu S, Lu T, Wang F, Yan F (2018) Molecular classification and subtype- specific characterization of skin cutaneous melanoma by aggregat- ing multiple genomic platform data. J Cancer Res Clin Oncol Jun 11. https ://doi.org/10.1007/s0043 2-018-2684-7 open in new tab
  40. Mahon BP, Pinard MA, McKenna R (2015) Targeting carbonic anhy- drase IX activity and expression. Molecules 20:2323-2348. https ://doi.org/10.3390/molec ules2 00223 23 open in new tab
  41. Maus A, Peters GJ (2017) Glutamate and α-ketoglutarate: key players in glioma metabolism. Amino Acids 49:21-32 open in new tab
  42. Najjar VA, Nishioka K (1970) "Tuftsin": a natural phagocytosis stimu- lating peptide. Nature 228(5272):672-673 open in new tab
  43. Nishioka K, Babcock GF, Phillips JH, Noyes RD (1981) Antitumor effect of tuftsin. Mol Cell Biochem 41:13-18 open in new tab
  44. Noyes RD, Babcock GF, Nishioka K (1981) Antitumor activity of tuft- sin on murine melanoma in vivo. Cancer Treat Rep 65:673-675
  45. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immuno- genicity of cancer cell death. Nat Med 13:54-61 open in new tab
  46. Othman S, Kozurkova M (2018) Sulfur containing acridine deriva- tives in preclinical studies with cancer cell lines. Curr Med Chem 25:1968-1975. https ://doi.org/10.2174/09298 67324 66617 04141 65019 open in new tab
  47. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807-1812 open in new tab
  48. Polewska J, Skwarska A, Augustin E, Konopa J (2013) DNA-damaging imidazoacridinone C-1311 induces autophagy followed by irre- versible growth arrest and senescence in human lung cancer cells. J Pharmacol Exp Ther 346:393-405. https ://doi.org/10.1124/ jpet.113.20385 1 (Epub 2013 Jul 3) open in new tab
  49. Polkowska M, Ekk-Cierniakowski P, Czepielewska E, Wysoczański W, Matusewicz W, Kozłowska-Wojciechowska MJ (2017) Survival of melanoma patients treated with novel drugs: retrospective analysis of real-world data. Cancer Res Clin Oncol; 143:2087-2094. https ://doi.org/10.1007/s0043 2-017-2453-z open in new tab
  50. Pommier Y, Covey J, Kerrigan D, Mattes W, Markovits J, Kohn KW (1987) Role of DNA intercalation in the inhibition of purified mouse leukemia (L1210) DNA topoisomerase II by 9-aminoacri- dines. Biochem Pharmacol 36:3477-3486 open in new tab
  51. Rastrelli M, Tropea S, Rossi CR, Alaibac M (2014) Melanoma: epide- miology, risk factors, pathogenesis, diagnosis and classification. In Vivo 28:1005-1011 open in new tab
  52. Sáez-Ayala M, Montenegro MF, Sánchez-Del-Campo L, Fernández- Pérez MP, Chazarra S, Freter R, Middleton M, Piñero-Madrona A, Cabezas-Herrera J, Goding CR, Rodríguez-López JN (2013) Directed phenotype switching as an effective antimelanoma strategy. Cancer Cell 24:105-119. https ://doi.org/10.1016/j. ccr.2013.05.009 open in new tab
  53. Scisłowski PW, Słominski A (1983) The role of NADP-dependent dehydrogenases in hydroxylation of tyrosine in hamster mela- noma. Neoplasma 30:239-243
  54. Searles SC, Santosa EK, Bui JD (2017) Cell-cell fusion as a mechanism of DNA exchange in cancer. Oncotarget 9:6156-6173 open in new tab
  55. Shibata T, Kokubu A, Miyamoto M, Sasajima Y, Yamazaki N (2011) Mutant IDH1 confers an in vivo growth in a melanoma cell line with BRAF mutation. Am J Pathol 178:1395-1402. https ://doi. org/10.1016/j.ajpat h.2010.12.011 open in new tab
  56. Siebert A, Gensicka-Kowalewska M, Cholewiński G, Dzierzbicka K (2017) Tuftsin-properties and analogs. Curr Med Chem 24:3711-3727 open in new tab
  57. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Man- delker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314(5797):268-274 open in new tab
  58. Skladanowski A (2002) Modulation of G(2) arrest enhances cell death induced by the antitumor 1-nitroacridine derivative. Nitracrine Apoptosis 7:347-359 open in new tab
  59. Slominska E, Carrey E, Foks H, Orlewska et al (2006) A novel nucleotide found in human erythrocytes 4-pyridone-3-carbox- iamide-1-beta-D-ribonucleoside triphosphate. J Biol Chem 281:32057-32064 open in new tab
  60. Smolewski P, Grabarek J, Halicka H, Darżynkiewicz Z (2002) Assay of caspase activation in situ combined with probing plasma mem- brane integrity to detect three distinct stages of apoptosis. J Immu- nol Methods 265:111-121 open in new tab
  61. Sniegocka M, Podgórska E, Płonka PM, Elas M, Romanowska-Dixon B, Szczygieł M, Żmijewski MA, Cichorek M, Markiewicz A, Brożyna AA, Słominski AT, Urbańska K (2018) Transplantable melanomas in hamsters and gerbils as models for human mela- noma. Sensitization in melanoma radiotherapy-from animal mod- els to clinical trials. Int J Mol Sci 19(4). https ://doi.org/10.3390/ ijms1 90410 48 open in new tab
  62. Stephens TC, Peacock JH (1982) Clonal variation in the sensitivity of B16 melanoma to m-AMSA. Br J Cancer 45:821-829 open in new tab
  63. Su TL, Chou TC, Kim JY, Huang JT, Ciszewska G, Ren WY, Otter GM, Sirotnak FM, Watanabe KA (1995) 9-substituted acrid- ine derivatives with long half-life and potent antitumor activ- ity: synthesis and structure-activity relationships. J Med Chem 38:3226-3235 open in new tab
  64. Svensson AL (2000) Tacrine interacts with different sites on nicotinic receptor subtypes in SH-SY5Y neuroblastoma and M10 cells. Behav Brain Res 113:193-197 open in new tab
  65. Swe T, Kim KB (2018) Update on systemic therapy for advanced cuta- neous melanoma and recent development of novel drugs. Clin Exp Metastasis. https ://doi.org/10.1007/s1058 5-018-9913-y open in new tab
  66. Syrjänen L, Luukkaala T, Leppilampi M, Kallioinen M, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila S, Karttunen T (2014) Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms. APMIS 122(9):880-889. https ://doi.org/10.1111/apm.12251 (Epub 2014 Apr 3) open in new tab
  67. Szutowicz A, Bielarczyk H, Gul S, Ronowska A, Pawełczyk T, Jankowska-Kulawy A (2006) Phenotype-dependent susceptibil- ity of cholinergic neuroblastoma cells to neurotoxic inputs. Metab Brain Dis 21:149-161 open in new tab
  68. Szutowicz A, Bielarczyk H, Jankowska-Kulawy A, Pawełczyk T, Ron- owska A (2013) Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases. Neurochem Res 38:1523-1542 open in new tab
  69. Tang SC, Lagas JS, Lankheet NA, Poller B, Hillebrand MJ, Rosing H, Beijnen JH, Schinkel AH (2012) Brain accumulation of sunitinib is restricted by P-glycoprotein (ABCB1) and breast cancer resist- ance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration. Int J Cancer 130:223-233. https ://doi. org/10.1002/ijc.26000 open in new tab
  70. Thomas NE, Kricker A, Waxweiler WT et al (2014) Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study. JAMA Dermatol 150:1306-1314 open in new tab
  71. Valter K, Zhivotovsky B, Gogvadze V (2018) Cell death-based treatment of neuroblastoma. Cell Death Dis 9:113. https ://doi. org/10.1038/s4141 9-017-0060-1 open in new tab
  72. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell prolifera- tion. Science 324(5930):1029-1033 open in new tab
  73. Wang J, Luo T, Li S, Zhhang Y, Wang C, Zhao J (2013) Synthesis, structure-activity relationship and biological activity of acridine derivatives as potent MDR-reversing agents. Curr Med Chem 20:4070-4079 open in new tab
  74. Warburg O (1958) The effect of hydrogen peroxide on cancer cells and on embryonic cells. Acta Unio Int Contra Cancrum 14:55-57 open in new tab
  75. Wardowska A, Dzierzbicka K, Myśliwski A (2007) Tuftsin-new ana- logues and properties. Post Biochem 53:60-65 open in new tab
  76. Yen KE, Bittinger MA, Su SM, Fantin VR (2010) Cancer-associated IDH mutations: biomarker and therapeutic opportunities. Onco- gene 29:6409-6417. https ://doi.org/10.1038/onc.2010.444 (Epub 2010 Oct 25) open in new tab
  77. Zielińska K, Kozłowska K, Cichorek M, Wachulska M (2008) Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties. Folia Histochem Cytobiol 46:337-343. https ://doi.org/10.2478/v1004 2-008-0041-4 open in new tab
  78. Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G (2010) Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res 16:3100-3104. https ://doi.org/10.1158/1078-0432.CCR-09-2891 open in new tab
Verified by:
Gdańsk University of Technology

seen 135 times

Recommended for you

Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents

2019

Chloroacridine derivatives as potential anticancer agents which may act as tricarboxylic acid cycle enzyme inhibitors

2020

Synthesis and Cholinesterase Inhibitory Activity of N-Phosphorylated /N-Tiophosphorylated Tacrine

2020

Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid

  • A. Siebert,
  • M. Deptuła,
  • M. Cichorek
  • + 3 authors
2021
Meta Tags