Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents - Publikacja - MOST Wiedzy


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


Acridine and acridone analogues were prepared by Ullmann condensation and then cyclization reaction. As a result of nucleophilic substitution reaction 1-nitro-9-phenoxyacridine or 1-chloro-4-nitro-9(10H)-acridone with the corresponding peptides, the planned acridine derivatives (10a-c, 12, 17-a-d, 19) have been obtained. The cytotoxic activity of the newly obtained analogs were evaluated against melanotic (Ma) and amelanotic (Ab) melanomacell lines and neuroblastoma SH-SY5Y by using the XTT method. Apoptosis and cell cycle were analyzed by flow cytometry. Among the investigated analogs compound 12 exhibited the highest potency comparable to dacarbazine action for amelanotic Ab melanoma cells. FLICA test (flurochrome-labeled inhibitors of caspases) showed that this analog significantly increased the content of cells with activated caspases (C+) among both neuroblastoma lines and only Ab melanoma line. Using phosphatidylserine (PS) externalization assay, 12 induced changes in the Ab melanoma plasma membrane structure as the externalization of phosphatidylserine (An+ cells). These changes in neuroblastoma cells were less pronounced. Analog 12 could be proposed as the new potential chemotherapeutic against amelanotic melanoma form especially.


  • 1


  • 1

    Web of Science

  • 2


Autorzy (6)

Cytuj jako

Pełna treść

pobierz publikację
pobrano 68 razy
Wersja publikacji
Accepted albo Published Version
Copyright (2018 Bentham Science Publishers)

Słowa kluczowe

Informacje szczegółowe

Publikacja w czasopiśmie
artykuły w czasopismach
Opublikowano w:
Medicinal Chemistry nr 15, strony 729 - 737,
ISSN: 1573-4064
Rok wydania:
Opis bibliograficzny:
Gensicka-Kowalewska M., Cichorek M., Ronowska A., Deptuła M., Klejbor I., Dzierzbicka K.: Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents// Medicinal Chemistry -Vol. 15, (2019), s.729-737
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.2174/1573406414666181015145120
Bibliografia: test
  1. Barot, K.P.; Nikolova, S.; Ivanov, I.; Ghate, M.D. Novel anticancer agents and targets: recent advances and future perspectives. Mini Rev. Med. Chem., 2013, 13, 1239-1255. otwiera się w nowej karcie
  2. Kaplan-Ozen, C.; Tekiner-Gulbas, B.; Foto, E.; Yildiz, I.; Diril, N.; Aki, E.; Yalcin, I. Benzothiazole derivatives as human DNA topoi- somerase II alpha inhibitors. Med. Chem. Res., 2013, 22, 5798- 5808. otwiera się w nowej karcie
  3. Prasad, V.V.S.R.; Reddy, G.D.; Kathmann, I.; Amareswararao, M. Peters, G.J. Nitric oxide releasing acridone carboxamide deriva- tives as reverters of doxorubicin resistance in MCF7/Dx cancer cells. Bioorg. Chem., 2016, 64, 51-58.
  4. Geddes, C.D. Optical thin film polymeric sensors for the determi- nation of aqueous chloride, bromide and iodide ions at high pH, based on the quenching of fluorescence of two acridinium dyes. Dyes Pigm., 2000, 45, 243-251. otwiera się w nowej karcie
  5. Dana, S.; Prusty, D.; Dhayal, D.; Gupta, M.K.; Dar, A.; Sen, S.; Mukhopadhyay, P.; Adak, T.; Dhar, S.K. Potent antimalarial activ- ity of acriflavine in vitro and in vivo. ACS Chem. Biol., 2014, 9, 2366-2373. otwiera się w nowej karcie
  6. Di Giorgio, C.; De Meo, M.; Chiron, J.; Delmas, F.; Nikoyan, A.; Jean, S.; Dumenil, G.; Timon-David, P.; Galy, J.P. Synthesis and antileishmanial activities of 4,5-di-substituted acridines as com- pared to their 4-mono-substituted homologues. Bioorg. Med. Chem., 2005, 13, 5560-5568.
  7. Gamega, S.A.; Spicer, J.A.; Atwell, G.J.; Finlay, G.J.;Baguley, B.C.; Denny, W.A. Structure-activity relationships for substituted bis(acridine-4-carboxamides): A new class of anticancer agents.J. Med. Chem., 1999, 42, 2383-2393.
  8. Gensicka-Kowalewska, M.; Cholewi ski, G.; Dzierzbicka, K. Recent developments in the synthesis and biological activity of acridine/acridone analogues.RSC Advances, 2017, 7, 15776-15804. otwiera się w nowej karcie
  9. Malachowska-Ugarte, M.; Cholewinski, G.; Dzierzbicka, K.; Trzonkowski, P. Synthesis and biological activity of novel myco- phenolic acid conjugates containing nitro-acridine/acridone deriva- tives. Eur. J. Med. Chem., 2012, 54, 197-201. otwiera się w nowej karcie
  10. Kukowska, M. Amino acid or peptide conjugates of acridine/ acri- done and quinoline/quinolone-containing drugs. A critical exami- nation of their clinical effectiveness within a twenty-year timeframe in antitumor chemotherapy and treatment of infectious diseases. Eur. J. Pharm. Sci., 2017, 109, 587-615. otwiera się w nowej karcie
  11. Kukowska-Kaszuba, M.; Dzierzbicka, K. Synthesis and structure- activity studies of peptide-acridine/ acridone conjugates. Curr. Med. Chem., 2007, 14, 3079-3104. otwiera się w nowej karcie
  12. Siebert, A.; Gensicka-Kowalewska, M.; Cholewi ski, G.; Dzierz- bicka, K. Tuftsin -properties and analogs. Curr. Med. Chem., 2017, 24, 3711-3727. otwiera się w nowej karcie
  13. Cichorek, M.; Koz owska, K.; Bryl, E. The activity of caspases in spontaneous and camptothecin-induced death of melanotic and am- elanotic melanoma cells. Cancer Biol. Ther., 2007, 6, 346-353. otwiera się w nowej karcie
  14. Kofoed, T.; Hansen, H.F.; Ørum, H.; Koch, T. PNA synthesis using a novel Boc/acyl protecting group strategy. J. Pept. Sci., 2001, 7, 402-412. otwiera się w nowej karcie
  15. Dzierzbicka, K.; Trzonkowski, P.; Sewerynek, P.; Kolodziejczyk, A.M.; My liwski, A. Synthesis and biological activity of tuftsin, its analogue and conjugates containing muramyl dipeptides or nor- muramyl dipeptides. J. Pept. Sci., 2005, 11, 123-135. otwiera się w nowej karcie
  16. Dzierzbicka, K.; Wardowska, A.; Rogalska, M.; Trzonkowski, P. New conjugates of muramyl dipeptide and nor-muramyl dipeptide linked to tuftsin and retro-tuftsin derivatives significantly influence their biological activity. Pharmacol. Rep., 2012, 64, 217-223.
  17. Januchta, W.; Serocki, M.; Dzierzbicka, K.; Cholewinski, G.; Skladanowski, A. Synthesis of functionalized new conjugates of batracylin with tuftsin/retro-tuftsin derivatives and their biological evaluation. Eur. J. Med. Chem., 2015, 106, 85-94. otwiera się w nowej karcie
  18. Ledochowski, A. Ledacrin -anticancerous medicine 1-nitro-9(3- dimethyloamino-propylamino)-acridine-2HCl-H2O. Mater. Med. Pol., 1976, 8, 237-251.
  19. Capps, D.B. Substituted 1-amino-4-nitroacridinones, pharmaceuti- cal compositions comprising the same and processes for their pro- duction. European Patent E.P. 0145226, October 31, 1984. otwiera się w nowej karcie
  20. Dzierzbicka, K.; Ko odziejczyk, A.M.; Wysocka-Skrzela, B.; My liwski, A.; Sosnowska, D. Synthesis and antitumor activity of conjugates of muramyldipeptide, normuramyl dipeptide, and des- muramylpeptides with acridine/acridone derivatives. J. Med. Chem., 2001, 44, 3606-3615. otwiera się w nowej karcie
  21. Bomirski, A.; Slominski, A.; Bigda, J. The natural history of a family of transplantable melanomas in hamsters. Cancer Metastasis Rev., 1988, 7, 95-118. otwiera się w nowej karcie
  22. Bielarczyk, H.; Jankowska, A.; Madziar, B.; Matecki, A.; Michno, A.; Szutowicz, A. Differential toxicity of nitric oxide, aluminum, and amyloid b-peptide in SN56 cholinergic cells from mouse sep- tum.Neurochem. Int., 2003, 42, 323-331. otwiera się w nowej karcie
  23. Synthesis and Biological Evaluation of Acridine/Acridone Analogs Medicinal Chemistry, 2018, Vol. 14, No. 00 9 otwiera się w nowej karcie
  24. Smolewski, P.; Grabarek, J.; Halicka, H.D.; Darzynkiewicz, Z. Assay of caspase activation in situ combined with probing plasma membrane integrity to detect three distinc stages of apoptosis. J. Immunol. Methods, 2002, 265, 111-121. otwiera się w nowej karcie
  25. Dar ynkiewicz, Z.; Williamson, B.; Carswell, E.; Old, L. Cell cycle-specific effects of tumor necrosis factor. Cancer Res., 1984, 44, 83-90.
  26. Guo, H.F.; Kooi, C.W.V.. Neuropilin functions as an essential cell surface receptor. J. Biol. Chem., 2015, 290, 29120-26. otwiera się w nowej karcie
  27. Graziani, G.; Lacal, P.M.. Neuropilin-1 as therapeutic target for malignant melanoma. Front Oncol., 2015, 5, 125-129. otwiera się w nowej karcie
  28. DISCLAIMER: The above article has been published in Epub (ahead of print) on the basis of the materials provided by the author. The Edito- rial Department reserves the right to make minor modifications for further improvement of the manuscript. otwiera się w nowej karcie
Politechnika Gdańska

wyświetlono 103 razy

Publikacje, które mogą cię zainteresować

Meta Tagi