New antimalarial agents derived from nonlinear phenoxazine ring system
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In vivo antimalarial screening of nine nonlinear phenoxazine compounds was carried out on the blood stages of Plasmodium berghei using standard methods. The activities of the compounds were compared with that of quinine as a standard antimalarial drug. LD50 and histopathological studies were also done. Molecular docking studies were carried out on four different protein targets of Plasmodium spp. The effects of these compounds on the hematological parameters (Hemoglobin, Hb; packed cell volume, PCV; white blood cells, WBC; and red blood cells, RBC) were also evaluated. The in vivo antimalarial studies showed that all the synthesized compounds had significant parasitaemia load reduction (89.00–94.05%) at 200 mg/ml when compared with the control, with (2-aminophenoxyl)benzo[a]phenoxazin-5-one 3b showing the highest activity. There was no significant difference in the activities of these compounds compared with the standard drug used (96%). The LD50 was found to be ≥5000 mg/kg. Histopathological studies showed a significant restoration of the liver intoxicated with malaria parasite after 5 days. The hematological analysis showed normal values for Hb, PCV, WBC, and RBC in the course of the treatment. The compounds showed more binding affinities for the P. falciparum receptors than the standard drug. The nine synthesized nonliner phenoxazine compounds had significant antimalarial activities and did not significantly affect the hematological parameters. They showed strong binding affinity to the parasite receptors. Hence, they are good candidates for antimalarial drugs. More preclinical investigations are needed.
KeywordsNonlinear phenoxazine Plasmodium spp Binding affinity Molecular docking Antimalarial Parasitaemia
number of rotatable bonds
number of hydrogen bond acceptors
number of hydrogen bond donors
number of violation
total polar surface area
packed cell volume
red blood cell
white blood cell
The authors are grateful to the faculty of Veterinary Medicine Department of University of Nigeria, Nsukka for providing the malaria parasite—Plasmodium berghei used in the study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conlict of interest.
The ethical clearance to use rats was in accordance with the University of Nigeria Ethics Committee on the use of laboratory animals, registered by the National Health Research Ethics Committee (NHREC) of Nigeria, with the number; NHREC/05/01/2008B.
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