Antiproliferative evaluation of various aminoquinoline derivatives

Zorc, Branka; Rajić, Zrinka; Perković, Ivana

doi:10.2478/acph-2019-0048

Abstract

Four classes of aminoquinoline derivatives were prepared: primaquine ureas 1a–f, primaquine bis-ureas 2a–f, chloroquine fumardiamides 3a–f and mefloquine fumardiamides 4a–f. Their antiproliferative activities against breast adeno-carcinoma (MCF-7), lung carcinoma (H460) and colon carcinoma (HCT 116 and SW620) cell lines were evaluated in vitro, using MTT cell proliferation assay. The results revealed a low activity of primaquine urea and bis-urea derivatives and high activity of all fumardiamides, with IC₅₀ values in low micromolar range against all tested cancer cell lines.

References

1. T. I. Oprea and J. Mestres, Drug repurposing: Far beyond new targets for old drugs, AAPS J.14 (2012) 759–763.10.1208/s12248-012-9390-1
Search in Google Scholar Back to article
2. T. T. Ashburn and K. B. Thor, Drug repositioning: identifying and developing new uses for existing drugs, Nat. Rev. Drug Discov.3 (2004) 673–683; https://doi.org/10.1038/nrd146810.1038/nrd146815286734
Search in Google Scholar Back to article
3. V. R. Solomon and H. Lee, Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies, Eur. J. Pharmacol.625 (2009) 220–233; https://doi.org/10.1016/j.ejphar.2009.06.06310.1016/j.ejphar.2009.06.06319836374
Search in Google Scholar Back to article
4. R. Duffy, C. Wade and R. Chang, Discovery of anticancer drugs from antimalarial natural products: a MEDLINE literature review, Drug Discov. Today17 (2012) 942–953.; https://doi.org/10.1016/j.drudis.2012.03.01310.1016/j.drudis.2012.03.01322504324
Search in Google Scholar Back to article
5. T. Kimura, Y. Takabatake, A. Takahashi and Y. Isaka, Chloroquine in cancer therapy: A double-edged sword of autophagy, Cancer Res.73 (2013) 3–7; https://doi.org/10.1158/0008-547210.1158/0008-5472.CAN-12-2464
Search in Google Scholar Back to article
6. R. H. van Huijsduijnen, R. Kiplin Guy, K. Chibale, R. K. Haynes, I. Peitz, G. Kelter, M. A. Phillips, J. L. Vennerstrom, Y. Yuthavong and T. N. C. Wells, Anticancer properties of distinct antimalarial drug classes, PLoS One8 (2013) e82962.10.1371/journal.pone.0082962387700724391728
Search in Google Scholar Back to article
7. A. K. Abdel-Aziz, S. Shouman, E. El-Demerdash, M. Elgendy and A. B. Abdel-Naim, Chloroquine as a promising adjuvant chemotherapy together with sunitinib, Sci. Proc.1 (2014) Article ID e384; https://doi.org/10.14800/sp.38410.14800/sp.384
Search in Google Scholar Back to article
8. F. Liu, Y. Shang and S.-Z. Chen, Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro, Acta Pharmacol. Sin. 35 (2014) 645–652; https://doi.org/10.1038/aps.2014.310.1038/aps.2014.3481403824727941
Search in Google Scholar Back to article
9. A. R. Choi, J. H. Kim, Y. H. Woo, H. S. Kim and S. Yoon, Anti-malarial drugs primaquine and chloroquine have different sensitization effects with anti-mitotic drugs in resistant cancer cells, Anticancer Res. 36 (2016) 1641–1648.10.21873/anticanres.11171
Search in Google Scholar Back to article
10. A. Ganguli, D. Choudhury, S. Datta, S. Bhattacharya and G. Chakrabarti, Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis, Biochimie107 (2014) 338–349; https://doi.org/10.1016/j.biochi.2014.10.00110.1016/j.biochi.2014.10.00125308836
Search in Google Scholar Back to article
11. C. Verbaanderd, H. Maes, M. B. Schaaf, V. P. Sukhatme, P. Pantziarka, V. Sukhatme, P. Agostinis and G. Bouche, Repurposing drugs in oncology (ReDO) – chloroquine and hydroxychloroquine as anti-cancer agents, eCancer11 (2017) Article ID 781; https://doi.org/10.3332/ecancer.2017.78110.3332/ecancer.2017.781571803029225688
Search in Google Scholar Back to article
12. F. Wang, J. Tang, P. Li, S. Si, H. Yu, X. Yang, J. Tao, Q. Lv, M. Gu, H. Yang and Z. Wang, Chloroquine enhances the radiosensitivity of bladder cancer cells by inhibiting autophagy and activating apoptosis, Cell. Physiol. Biochem.45 (2018) 54–66; https://doi.org/10.1159/00048622210.1159/00048622229316551
Search in Google Scholar Back to article
13. L. Liu, C. Han, H. Yu, W. Zhu, H. Cui, L. Zheng, C. Zhang and L. Yue, Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial-mediated apoptosis, Oncol. Rep.39 (2018) 2807–2816.
Search in Google Scholar Back to article
14. A. Kamal A. Aziz, S. Shouman, E. El-Demerdash, M. Elgendy and A. B. Abdel-Naim, Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries, Chem. Biol. Interact.217 (2014) 28–40; https://doi.org/10.1016/j.cbi.2014.04.00710.1016/j.cbi.2014.04.00724751611
Search in Google Scholar Back to article
15. G. W. Soo, J. H. Law, E. Kan, S. Y. Tan, W. Y. Lim, G. Chay, N. I. Bukhari and I. Segarra, Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice, Anticancer Drugs21 (2010) 695–703.10.1097/CAD.0b013e32833c93b3
Search in Google Scholar Back to article
16. Y. K. Wong, C. Xu, K. A. Kalesh, Y. He, Q. Lin, W. S. F. Wong, H. M. Shen and J. Wang, Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action, Med. Res. Rev.37 (2017) 1492–1517.10.1002/med.21446
Search in Google Scholar Back to article
17. https://clinicaltrials.gov/ct2/home (last access May 26, 2019)
Search in Google Scholar Back to article
18. https://en.wikipedia.org/wiki/WHO_Model_List_of_Essential_Medicines (last access May 27, 2019)
Search in Google Scholar Back to article
19. N. Vale, R. Moreira and P. Gomes, Primaquine revisited six decades after its discovery, Eur. J. Med. Chem.44 (2009) 937–953; https://doi.org/10.1016/j.ejmech.2008.08.01110.1016/j.ejmech.2008.08.01118930565
Search in Google Scholar Back to article
20. P. M. Njaria, J. Okombo, N. M. Njuguna and K. Chibale, Chloroquine-containing compounds: a patent review (2010 – 2014), Expert Opin. Therap. Patents25 (2015) 1003–1024; https://doi.org/10.1517/13543776.2015.105079110.1517/13543776.2015.1050791710371026013494
Search in Google Scholar Back to article
21. S-J. Yeo, D-X. Liu, H-S. Kim and H. Park, Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria, Malaria J.16 (2017) 80; https://doi.org/10.1186/s12936-017-1725-z10.1186/s12936-017-1725-z531621328212631
Search in Google Scholar Back to article
22. M. A. Avery, D. J. Weldon and K. M. Muraleedharan, Advances in the Discovery of New Antimalarials, in Comprehensive Medicinal Chemistry II (Eds. J. B. Taylor and D. J. Triggle), Vol. 7, Elsevier Ltd., 2007, pp. 765–814; https://doi.org/10.1016/B0-08-045044-X/00227-310.1016/B0-08-045044-X/00227-3
Search in Google Scholar Back to article
23. K. Pavić, Z. Rajić, Z. Mlinarić, L. Uzelac, M. Kralj and B. Zorc, Chloroquine urea derivatives: synthesis and antitumor activity in vitro, Acta Pharm. 68 (2018) 471–483.10.2478/acph-2018-0039
Search in Google Scholar Back to article
24. M. Beus, L. Persoons, D. Schols, L. Uzelac, M. Kralj, Z. Rajić and B. Zorc, Cytotoxicity studies of primaquine and chloroquine fumardiamides, 6th Croatian Congress on Pharmacy with International Participation, Book of Abstract, PO-16, Dubrovnik, April 4–6, 2019
Search in Google Scholar Back to article
25. M. Beus, D. Fontinha, J. Held, Z. Rajić, M. Prudêncio and B. Zorc, Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides, Acta Pharm. 69 (2019) 233–248; https://doi.org/10.2478/acph-2019-001910.2478/acph-2019-001931259728
Search in Google Scholar Back to article
26. G. Džimbeg, B. Zorc, M. Kralj, K. Ester, K. Pavelić, J. Balzarini, E. De Clercq and M. Mintas, The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: synthesis, cytostatic and antiviral activity evaluations, Eur. J. Med. Chem.43 (2008) 1180–1187; https://doi.org/10.1016/j.ejmech.2007.09.00110.1016/j.ejmech.2007.09.00117961851
Search in Google Scholar Back to article
27. M. Šimunović, I. Perković, B. Zorc, K. Ester, M. Kralj, D. Hadjipavlou-Litina and E. Pontiki, Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities, Bioorg. Med. Chem.17 (2009) 5605–5613; https://doi.org/10.1016/j.bmc.2009.06.03010.1016/j.bmc.2009.06.03019581098
Search in Google Scholar Back to article
28. I. Perković, S. Tršinar, J. Žanetić, M. Kralj, I. Martin-Kleiner, J. Balzarini, D. Hadjipavlou-Litina and A. M. Katsori, Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine – synthesis, cytostatic, antiviral and antioxidative studies, J. Enzyme Inhib. Med. Chem.28 (2013) 601–610; https://doi.org/10.3109/14756366.2012.66336610.3109/14756366.2012.66336622380782
Search in Google Scholar Back to article
29. K. Pavić, I. Perković, M. Cindrić, M. Pranjić, I. Martin-Kleiner, M. Kralj, D. Schols, D. Hadjipavlou-Litina, A.-M. Katsori and B. Zorc, Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: Synthesis, cytostatic and antioxidative activity, Eur. J. Med. Chem.86 (2014) 502–514; https://doi.org/10.1016/j.ejmech.2014.09.01310.1016/j.ejmech.2014.09.01325203780
Search in Google Scholar Back to article
30. I. Perković, M. Antunović, I. Marijanović, K. Pavić, K. Ester, M. Kralj, J. Vlainić, I. Kosalec, D. Schols, D. Hadjipavlou-Litina, E. Pontiki and B. Zorc, Novel urea and bis-urea primaquine derivatives with hydroxyphenyl and halogenphenyl substituents: synthesis and biological evaluation, Eur. J. Med. Chem.124 (2016) 622–636; https://doi.org/10.1016/j.ejmech.2016.08.02110.1016/j.ejmech.2016.08.02127614409
Search in Google Scholar Back to article
31. K. Pavić, I. Perković, P. Gilja, F. Kozlina, K. Ester, M. Kralj, D. Schols, D. Hadjipavlou-Litina, E. Pontiki and B. Zorc, Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of amide and acylsemicarbazide type, Molecules21 (2016) 1629–1653; https://doi.org/10.3390/molecules2112162910.3390/molecules21121629627368727916811
Search in Google Scholar Back to article
32. K. Pavić, I. Perković, Š. Pospíšilová, M. Machado, D. Fontinha, M. Prudêncio, J. Jampilek, A. Coffey, L. Endersen, H. Rimac and B. Zorc, Primaquine hybrids as promising antimycobacterial and antimalarial agents, Eur. J. Med. Chem.143 (2018) 769–779; https://doi.org/10.1016/j.ejmech.2017.11.08310.1016/j.ejmech.2017.11.08329220797
Search in Google Scholar Back to article
33. J. Vlainić, I. Kosalec, K. Pavić, D. Hadjipavlou-Litina, E. Pontiki and B. Zorc, Insights into biological activity of ureidoamides with primaquine and amino acid moieties, J. Enzyme Inhib. Med. Chem.33 (2018) 376–382; https://doi.org/10.1080/14756366.2017.142306710.1080/14756366.2017.1423067602103529363364
Search in Google Scholar Back to article
34. J. Levatić, K. Pavić, I. Perković, L. Uzelac, K. Ester, M. Kralj, M. Kaiser, M. Rottmann, F. Supek and B. Zorc, Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity, Eur. J. Med. Chem.146 (2018) 651–667; https://doi.org/10.1016/j.ejmech.2018.01.06210.1016/j.ejmech.2018.01.06229407988
Search in Google Scholar Back to article
35. M. Beus, Z. Rajić, D. Maysinger, Z. Mlinarić, M. Antunović, I. Marijanović, D. Fontinha, M. Prudêncio, J. Held, S. Olgen and B. Zorc, SAHAquines, novel hybrids based on SAHA and primaquine motifs, as potential anticancer and antiplasmodial agents, ChemistryOpen7 (2018) 624–638; https://doi.org/10.1002/open.20180011710.1002/open.201800117610443330151334
Search in Google Scholar Back to article
36. Z. Rajić, M. Beus, H. Michnova, J. Vlainić, L. Persoons, I. Kosalec, J. Jampilek, D. Schols, T. Keser and B. Zorc, Asymmetric primaquine and halogenaniline fumardiamides as novel biologically active Michael acceptors, Molecules23 (2018) 1724; https://doi.org/10.3390/molecules2307172410.3390/molecules23071724610058230011922
Search in Google Scholar Back to article
37. I. Zhang, M. Beus, U. Stochaj, P. U. Le, B. Zorc, Z. Rajić, K. Petrecca and D. Maysinger, Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action of a novel hydroxamic acid hybrid molecule, Cell Death Discov. 5 (2019) 41; https://doi.org/10.1038/s41420-018-0103-010.1038/s41420-018-0103-0615828830302275
Search in Google Scholar Back to article
38. K. Pavić, Z. Rajić, H. Michnová, J. Jampílek, I. Perković and B. Zorc, Second generation of primaquine ureas and bis-ureas as potential antimycobacterial agents, Mol. Diver. (2018); https://doi.org/10.1007/s11030-018-9899-z10.1007/s11030-018-9899-z30523579
Search in Google Scholar Back to article
39. M. E. Flanagan, J. A. Abramite, D. P. Anderson, A. Aulabaugh, U. P. Dahal, A. M. Gilbert, C. Li, J. Montgomery, S. R. Oppenheimer, T. Ryder, B. P. Schuff, D. P. Uccello, G. S. Walker, Y. Wu, M. F. Brown, J. M. Chen, M. M. Hayward, M. C. Noe, R. S. Obach, L. Philippe, V. Shanmugasundaram, M. J. Shapiro, J. Starr, J. Stroh and Y. Che, Chemical and computational methods for the characterization of covalent reactive groups for the prospective design of irreversible inhibitors, J. Med. Chem.57 (2014) 10072–10079; https://doi.org/10.1021/jm501412a10.1021/jm501412a25375838
Search in Google Scholar Back to article
40. I. Fernandes, N. Vale, V. de Freitas, R. Moreira, N. Mateus and P. Gomes, Anti-tumoral activity of imidazoquines, a new class of antimalarials derived from primaquine, Bioorg. Med. Chem. Lett.19 (2009) 6914–6917; https://doi.org/10.1016/j.bmcl.2009.10.08110.1016/j.bmcl.2009.10.08119896373
Search in Google Scholar Back to article
41. T. Rossi, A. Coppi, E. Bruni, A. Ruberto, S. Santachiara and G. A. Baggio, Effects of anti-malarial drugs on MCF-7 and Vero cell replication, Anticancer Res. 27 (2007) 2555–2559.
Search in Google Scholar Back to article
42. A. R. Martirosyan, R. Rahim-Bata, A. B. Freeman, C. D. Clarke, R. L. Howard and J. S. Strobl, Differentiation-inducing quinolines as experimental breast cancer agents in the MCF-7 human breast cancer cell model, Biochem. Pharmacol. 68 (2004) 1729–1738.10.1016/j.bcp.2004.05.00315450938
Search in Google Scholar Back to article

Antiproliferative evaluation of various aminoquinoline derivatives

Abstract

Paradigm

My account