Antimalarial activity of amodiaquine-moxifloxacin: A study in mice.

Year 2023, Volume: 4 Issue: 1, 1 - 6, 31.01.2023

Elias Adıkwu , Confidence Orgechi Nworgu Simeon Igono Ajeka

https://doi.org/10.47482/acmr.1140050

Abstract

Background: The search for new partner drugs to increase the therapeutic activity of existing antimalarial drugs is important because of decreased Plasmodium susceptibility. Amodiaquine (AQ) is an antimalarial drug. Moxifloxacin (MX) is a fluoroquinolone antibiotic with promising antiplasmodial activity. This study evaluated the benefit of MX as a partner drug with AQ for malaria treatment in Plasmodium berghei-infected mice. Methods: Adult Swiss albino mice (28-35g) of both sexes, randomly grouped and inoculated with Plasmodium berghei were used. The mice were treated orally with AQ (10 mg/kg), MX (6 mg/kg) and AQ-MX, respectively using the curative, prophylactic and suppressive protocols. Blood samples were collected and assessed for percentage parasitemia and hematological indices. Liver samples were assessed for histological changes. Mean survival time (MST) was observed in treated mice. Results: The curative, prophylactic and suppressive tests showed that AQ-MX decreased percentage parasitemia with difference observed at p<0.05 when compared to AQ or MX. In the curative test, AQ, MX and AQ-MX produced 70.9 %, 65. 0% and 90.6% parasitemia inhibitions, respectively whereas CQ (Standard) produced 87.9 % parasitemia inhibition. AQ-MX prolonged MST with difference observed at p<0.05 in the curative, prophylactic and suppressive tests when compared to AQ or MX. The restored hematological indices caused by AQ-MX were characterized by increased hemoglobin, red blood cells, and packed cell volume with decreased white blood cells observed at p<0.05 when compared to AQ or MX. AQ-MX eradicates liver merozoites. Conclusion: MX may be an effective partner drug with AQ for malaria treatment.

Keywords

Amodiaquine, moxifloxacin, Antimalaria, partner-drug, Plasmodium, mice.

References

• 1. World Health Organization. Official records of WHO. No. 184, 23rd WH Assen. Geneva, World Health Organization 1970.
• 2. Taylor C, Florey L, Ye Y. Equity trends in ownership of insecticides treated nets in Sub-Sahara Africa Countries. Bull. WHO 2017; 95: 322-322.
• 3. World Health Organization Global technical strategy for malaria 2016-2030
• 4. World Health Organization. Guideline for the treatment of malaria. Geneva, World Health Organization 2015.
• 5. Menard D, Dondorp AR.Antimalarial drug resistance: A threat to malaria elimination. Cold spring Herb Pers Med, 2017; 7(7): a025619. 6. White NJ. Antimalarial drug resistance. J Clin Invest. 2004, 113(8):1084-1092.
• 7. Smith, D.L., Klein, E.Y., McKenzie, F.E. et al. Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty. Malar J 2010. 9, 217. 1-10
• 8. Fairhurst RM, Dondrp AM. Artemisinin resistance plasmodium falciparum malaria. Microb Spect 2016; 4-13.
• 9. World Health Organization. Guidelines for the treatment of malaria. Geneva. World Health Organization, 2006.
• 10. Nair A, Abrahamsson B, Bardends DM, Groot DW, Kopp S et al Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine hydrochloride. J Pharmac Sci. 2012; 101(12): 4390-401.
• 11. World Health Organization. Seasonal malaria chemoprevention with sulfadoxine-pyrithamine plus amodiaquine in children. A field guide.Geneva. World Health Organization , 2013.
• 12. Amodiaquine from the Origin 2016; retrieved 22 Sep, 2021.
• 13. Moxifloxacin thydrochloride. The America Society of health system pharmacists. Retrieved 22 Sep, 2021.
• 14. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolines. Micro Mol Biol Rev. 1998; 61(3),377-92.
• 15. Yadav K, Shivahare R, Shaham SH, Joshi P, Sharma A et al. Repurposing of existing therapeutics to combat drug-resistant malaria, Biomed & Pharmacother, 2021, 136, 111275,
• 16. Somsak V, Damkaew A, Onrak P. Antimalarial Activity of Kaempferol and Its Combination with Chloroquine in Plasmodium berghei Infection in Mice. J. Path. 2018;1-7.
• 17. Gaillard T, Madamet M, Tsombeng FF, Dormoi J, Pradines B. Antibiotics in malaria therapy: Which antibiotics except tetracyclines and macrolides may be used against malaria? Malar. J. 2016; 15: 1–10.
• 18. Yavo W, Faye B, Kuete T, Djohan V, Oga SA et al. Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemetherlumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa. Malar J, 2011; 10:198.
• 19. Ryley J, Peters W. The antimalarial activity of some quinolone esters. Ann of Trop Med & Parasit , 1970; 84:209–222.
• 20. Peters W. The value of drug-resistant strains of Plasmodium berghei in screening for blood schizontocidal activity. Ann of Trop Med parasit 1975; 69(2): 155–171,
• 21. Knight D, Peters W. The antimalarial activity of N- benzyloxydihydrotriazines. Annals of Trop Med and Parasit. 1980; 74(4):393-404.
• 22. Bahekar S, Kale R. Herbal plants used for the treatment of malaria – a Literature review. J Pharmacog and Phytochem. 2013; 8192: 141-146.
• 23. Birru, E.M., Geta, M, Gurmu, A.E. Antiplasmodial activity of Indigofera spicata root extract against Plasmodium berghei infection in mice. Malar J. 2017; 16, 198; 1-7
• 24. Olasehinde GI, Ojurongbe O, Adeyeba AO, Fagade OE, Valecha N et al. In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts. Malar J. 2014; 13:63.
• 25. Matthews, H., Usman-Idris, M., Khan, F. et al. Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate. Malar J, 2013 12; 359 https://doi.org/10.1186/1475-2875-12-35
• 26. Kalra B, Chawla S, Gupta P, Valecha N. Screening of antimalarial drugs: an overview. Indian J Pharmacol. 2006; 38 (1) 5–1.
• 27. Waakoab PJ, Gumedeb B, Smithb P, Folbb PI. The in vitro and in vivo antimalarial activity of Cardiospermum halicacabum and Momordica foetida,” J Ethnopharmacol, 2005; 99 (1)137–143.
• 28. Huang BW, Kim E, and Charles C. Mouse models of uncomplicated and fatal malaria. Bio-Protocol, 2015; 5, (13); 1514
• 29. Peter I and Anatoli V The current global malaria situation in Malaria Parasite Biology, Pathogenesis, and Protection, pp. 11–22, ASM Press, Washington, DC, USA, 1998.
• 30. DuPlessis LH, Govender K, Denti P, Wiesner L. In vivo efficacy and bioavailability of lumefantrine: Evaluating the application of Pheroid technology. Euro J Pharm and Biopharm. 2015; 97:68-77.
• 31. Anosa GN, Udegbunam RI, Okoro JO, Okoroafor ON. In vivo antimalarial activities of Enantia polycarpa stem bark against Plasmodium berghei in mice. J of Ethnopharm 2014; 153(2):531-4.
• 32. Georgewill UO, Ebong NO, Adikwu E. Antiplasmodial activity of desloratadine-dihydroartemisinin-piperaquine on Plasmodium berghei-infected mice Journal of Applied Biol & Biotech 2021; 9 (2) 69-73
• 33. Saxena R, Bhatia A, Midha K, Debnath M, Kaur P. Malaria: A Cause of Anemia and Its Effect on Pregnancy. World J Anemia 2017; 1(2):51-62.
• 34. Chinchilla M, Guerrero O, Abarca G, Barrios M, Castro O. An in vivo model to study the anti-malaria capacity of plant extracts. Rev Biol Trop. 1998; 46:1–7.
• 35. Adikwu E, Ajeka IS. Artemether/lumefantrine/clindamycin eradicates blood and liver stages of Plasmodium berghei infection in mice. J Analy and Pharm Res. 2021; 10 (6):240‒244.
• 36. Dubar F, Wintjens R, Martins-Duarte ES, Vommaro RC, Souza Wet al. Ester prodrugs of ciprofloxacin as DNA-gyrase inhibitors: synthesis, antiparasitic evaluation and docking studies. Med Chem Commun. 2021; 2:430–435.
• 37. Tang Girwood SC, Nenornas E, Shapiro TA. Targeting the gyrase of Plasmodium falciparum with topoisomerase poisons. Biochem Pharmacol. 2015; 95:227–237.