Phospholipid membranes are thought to be one of the main inducers of hemozoin formation in Plasmodia and other blood-feeding parasites. The "membrane surrounding hemozoin" has been observed in infected cells but has not been observed in in vitro experiments. This study focused on observing the association of phospholipid membranes and synthetic β-hematin, which is chemically identical to hemozo...

the formation of hemozoin (malaria pigment) has been proposed as an ideal drug target for antimalarial screening programs. in this study, we used an improved, cost-effective and high-throughput spectrophotometric assay to screen plant extracts for finding novel antimalarial plant sources. fifteen extracts with different polarity from three iranian artemisia species, a. ciniformis, a. biennis an...

Background: β-Hematin (Hemozoin) was synthised inside human erythrocyte by malaria parasite. The parasite avoids the toxic effects by polymerizing heme molecules into insoluble crystalline β-Hematin. C. botrys and A. annua used for the treatment of diseases like malaria, hepatitis, cancers, and inflammations. Objective: Determine of antimalarial and anti-protozoa effects of A. anuuae and C. bo...

malaria as one of the most recurrent infectious diseases caused by parasites of the genus plasmodium, kills several hundred thousand people especially in the tropical and subtropical regions of the world annually. terpenoids have served as the lead compounds to develop new antimalarial agents. the aromatic monoterpenoid, cuminaldehyde, isolated from the fruits of buniumpersicum was evaluated fo...

During their pathogenic blood stage, malaria parasites invade host erythrocytes where they digest hemoglobin. In the process, they release large quantities of potentially toxic hematin, which they convert to hemozoin. This is an insoluble microcrystalline product. The quinoline antimalarials, such as chloroquine form complexes with hematin and inhibit the formation of synthetic hemozoin (β-hema...

The emergence of drug resistant strains of Plasmodium spp. creates a critical need for the development of novel antimalarials. Formation of hemozoin, a crystalline heme detoxification process vital to parasite survival serves as an important drug target. The quinoline antimalarials including chloroquine and amodiaquine owe their antimalarial activity to inhibition of hemozoin formation. Though ...

The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected d...

A series of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Selected analogues were screened for their antitubercular activity against sensitive MTB H(37)Rv ...

Apoptosis in macrophages is responsible for immune-depression and pathological effects during malaria. Phagocytosis of PRBC causes induction of apoptosis in macrophages through release of cytosolic factors from infected cells. Heme polymer or β-hematin causes dose-dependent death of macrophages with LC50 of 132 µg/ml and 182 µg/ml respectively. The toxicity of hemin or heme polymer was amplifie...

Quinoline antimalarials target hemozoin formation causing a cytotoxic accumulation of ferriprotoporphyrin IX (Fe(III)PPIX). Well-developed SAR models exist for β-hematin inhibition, parasite activity, and cellular mechanisms for this compound class, but no comparably detailed investigations exist for other hemozoin inhibiting chemotypes. Here, benzamide analogues based on previous HTS hits have...