Skip to content
2000
image of Growth of Chloroquine Crystals and Their Properties as a Beta-hematin Inhibitor

Abstract

Introduction

The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation.

Materials and Methods

This study reports the synthesis of two novel CQ-derived compounds, 7-chloroquinolin-4-amine (CQC1) and 7-chloro-4-(1-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation.

Results

Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated.

Conclusion

The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ).

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010366828250623060543
2025-07-10
2025-10-16

  • From This Site

    /content/journals/cpb/10.2174/0113892010366828250623060543
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Al-Refai’a RAK Cowpea mosaic virus (CPMV) as a carrier vehicle for antimalarial drugs, modification and application. Int. J. Drug Deliv Technol 2019 9 490 495 10.25258/ijddt.v9i3.30
    [Google Scholar]
  2. Duguma T. Nuri A. Melaku Y. Prevalence of malaria and associated risk factors among the community of Mizan‐Aman town and its catchment area in Southwest Ethiopia. J. Parasitol. Res. 2022 2022 1 3503317 35464173
    [Google Scholar]
  3. Tarekegn M. Tekie H. Dugassa S. Wolde-Hawariat Y. Malaria prevalence and associated risk factors in Dembiya district, North-western Ethiopia. Malar. J. 2021 20 1 372 34535130
    [Google Scholar]
  4. Al-Refaia R.A. Alkarimi A.A. Synthesis and hemozoin inhibitor of side-chain modified copper-chloroquine derivatives. IOP Conf Ser: Mater. Sci. Eng 2020 987 012021
    [Google Scholar]
  5. Haines D.D. Tosaki A. Heme degradation in pathophysiology of and countermeasures to inflammation-associated disease. Int. J. Mol. Sci. 2020 21 24 9698 10.3390/ijms21249698 33353225
    [Google Scholar]
  6. Dinarvand P. Yang L. Biswas I. Giri H. Rezaie A.R. Plasmodium falciparum histidine rich protein HRPII inhibits the anti‐inflammatory function of antithrombin. J. Thromb. Haemost. 2020 18 6 1473 1483 10.1111/jth.14713 31858717
    [Google Scholar]
  7. Nhien N.T.T. Huy N.T. Uyen D.T. Deharo E. Hoa P.T.L. Hirayama K. Harada S. Kamei K. Effect of inducers, incubation time and heme concentration on IC50 value variation in anti-heme crystallization assay. Trop. Med. Health 2011 39 4 119 126 10.2149/tmh.2011‑29 22438701
    [Google Scholar]
  8. de Villiers K.A. Egan T.J. Heme detoxification in the malaria parasite: A target for antimalarial drug development. Acc. Chem. Res. 2021 54 11 2649 2659 10.1021/acs.accounts.1c00154 33982570
    [Google Scholar]
  9. Lewinska G. Sanetra J. Marszalek K.W. Application of quinoline derivatives in third-generation photovoltaics. J. Mater. Sci. Mater. Electron. 2021 32 14 18451 18465 10.1007/s10854‑021‑06225‑6 38624760
    [Google Scholar]
  10. Nammalwar B. Bunce R. Recent syntheses of 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. Molecules 2013 19 1 204 232 10.3390/molecules19010204 24368602
    [Google Scholar]
  11. Katritzky A.R. Rachwal B. Rachwal S. A versatile method for the preparation of substituted 1, 2, 3, 4-tetrahydroquinolines. J. Org. Chem. 1995 60 7631 7640 10.1021/jo00128a041
    [Google Scholar]
  12. Plantone D. Koudriavtseva T. Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review. Clin. Drug Investig. 2018 38 8 653 671 10.1007/s40261‑018‑0656‑y 29737455
    [Google Scholar]
  13. Egwu C.O. Tsamesidis I. Pério P. Augereau J.M. Benoit-Vical F. Reybier K. Superoxide: A major role in the mechanism of action of essential antimalarial drugs. Free Radic. Biol. Med. 2021 167 271 275 10.1016/j.freeradbiomed.2021.03.001 33722628
    [Google Scholar]
  14. Liu Z.Q. Han K. Lin Y.J. Luo X.Y. Antioxidative or prooxidative effect of 4-hydroxyquinoline derivatives on free-radical-initiated hemolysis of erythrocytes is due to its distributive status. Biochim. Biophys. Acta 2002 1570 2 97 103 11985893
    [Google Scholar]
  15. Miyachi Y. Yoshioka A. Imamura S. Niwa Y. Antioxidant action of antimalarials. Ann. Rheum. Dis. 1986 45 3 244 248 3006612
    [Google Scholar]
  16. Maes H. Kuchnio A. Carmeliet P. Agostinis P. Chloroquine anticancer activity is mediated by autophagy-independent effects on the tumor vasculature. Mol. Cell. Oncol. 2015 3 1 e970097 27308577
    [Google Scholar]
  17. Liang A-L. Zhang J. Chloroquine increases the anti-cancer activity of epirubicin in A549 lung cancer cells. Oncology Letters 2020 20 53 60 10.3892/ol.2020.11567 32565933
    [Google Scholar]
  18. Lawrenson A.S. Cooper D.L. O’Neill P.M. Berry N.G. Study of the antimalarial activity of 4-aminoquinoline compounds against chloroquine-sensitive and chloroquine-resistant parasite strains. J. Mol. Model. 2018 24 9 237 30120591
    [Google Scholar]
  19. Al-Khafaji Y. Tetraphenolate niobium and tantalum complexes for the ring opening polymerization of ε-caprolactone. Dalton Transactions 2015 44 12349 12356
    [Google Scholar]
  20. Wang X. Organoaluminium complexes derived from anilines or Schiff bases for the ring‐opening polymerization of ε‐caprolactone, δ‐valerolactone and rac‐lactide. Eur. J. Inorg. Chem. 2017 2017 1951 1965 10.1002/ejic.201601415
    [Google Scholar]
  21. Delarue-Cochin S. Grellier P. Maes L. Mouray E. Sergheraert C. Melnyk P. Synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline. Eur. J. Med. Chem. 2008 43 10 2045 2055 18226428
    [Google Scholar]
  22. Sullivan D.J. Gluzman I.Y. Russell D.G. Goldberg D.E. On the molecular mechanism of chloroquine’s antimalarial action. Proc. Natl. Acad. Sci. USA 1996 93 21 11865 11870 10.1073/pnas.93.21.11865 8876229
    [Google Scholar]
  23. Deharo E. García R.N. Oporto P. Gimenez A. Sauvain M. Jullian V. Ginsburg H. A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds. Exp. Parasitol. 2002 100 4 252 256 12128052
    [Google Scholar]
  24. Dorn A. Vippagunta S.R. Matile H. Bubendorf A. Vennerstrom J.L. Ridley R.G. A comparison and analysis of several ways to promote haematin (haem) polymerisation and an assessment of its initiation in vitro. Biochem. Pharmacol. 1998 55 6 737 747 9586945
    [Google Scholar]
  25. Gossuin Y. Okusa Ndjolo P. Vuong Q.L. Duez P. NMR relaxation properties of the synthetic malaria pigment β-hematin. Sci. Rep. 2017 7 1 14557 29109553
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010366828250623060543
Loading
Growth of Chloroquine Crystals and Their Properties as a Beta-hematin Inhibitor
Bentham Science Publishers ; https://doi.org/10.2174/0113892010366828250623060543
/content/journals/cpb/10.2174/0113892010366828250623060543
/content/journals/cpb/10.2174/0113892010366828250623060543
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: crystallization ; Beta-hematin ; heme ; hemozoin ; Crystallization ; antimalarial drugs

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test