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Malaria causes hundreds of thousands of human deaths every year, and the World Health Assembly has made it a priority. To help eliminate this disease, there is a pressing need for the development and implementation of new strategies to improve the prevention and treatment, due in part to antimalarial drug resistances. This chapter focuses on two st...
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... porphyrins have been studied for their use in heme aggregation inhibition. In 1997, Basilico et al. [127] evaluated the effect of two non-iron metalloporphyrins (PPIX and hematoporphyrin) on the crystallization of α-hematin (Figure 8) to β-hematin also called synthetic hemozoin (Figure 2). Crystallization of hematin may be achieved in 4.5 M sodium acetate buffer at 60°C [35]. ...
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... A porphyrin derivative was found to be active in vitro against Plasmodium falciparum at 20 nM and a slight delay of mice survival was observed on the Plasmodium berghei Swiss mice model at 50 µmol/kg/day. It was concluded that pharmacomodulations should be further developed to better understand porphyrin behavior in the parasites compared to host cells [171], [172]. ...
Photodynamic therapy (PDT) or light treatment is a procedure to treat certain types of diseases that uses a photosensitizer (PS) which upon light activation produces cytotoxic oxygen species destroying tumor cells. PDT is minimally-invasive and can be repeated a few times without accumulating significant toxicity in the surrounding tissues. While PDT application in cancer treatment is well established and widely recognized by the scientific community, and its use in the fight against microbial infection is gaining momentum with the rapid increase in antimicrobial multi-drug resistance, its use in the treatment of cardiovascular diseases is clearly marginal. This mini-review presents a brief historical background of PDT, photo-activatable agents utilized, mechanism of photodynamic action, studies in vitro and in vivo, clinical trials, limitations and future prospects of its application in various types of cancer, infections caused by pathogens such as COVID-19, and heart diseases.
... Phytochemicals with such inhibitory activity against heme-hemozoin conversion include alkaloids classes such as quinine, quinidine, cinchonine, and cinchonidine [60,61]. Furthermore, the antiplasmodial activities of several anthraquinones, phenolics, and flavonoids could be linked to their ability to form Biochemistry Research International π-π stacking interaction with heme leading to binding and subsequent inhibition of hemozoin formation in the parasite [62][63][64]. e major pharmacophore responsible for the activity of these phytocompounds is due to the presence of multiple phenolic systems in their structures. Specific phytocompounds identified to follow this mechanism of action include rufigallol, exifone, apigenin, ellagic acid, and derivatives [65][66][67]. ...
Background:
Afzelia africana is a plant species with reported numerous medicinal potentials and secondary metabolites. Various parts of the plant have been applied for the treatment of hernia, rheumatism, pain, lumbago, malaria, etc. The study seeks to evaluate the phytochemical constituents, antiplasmodial, and ESI-MS scan of bioassay-guided fractions from the methanol extract of the bark of the plant.
Aims:
The main aim of the study was to carry out bioassay-guided fractionation of the crude methanol extract of Afzelia africana in order to isolate fractions and to evaluate their antiplasmodial activities and ESI-MS fingerprints.
Methods:
The methods employed include column chromatographic fractionation, phytochemical screening, antiplasmodial activity (malaria SYBER green assay (MSF)), and ESI-MS profile (full ESI-MS scan).
Results:
The column chromatographic fractionation and phytochemical screening of the plant led to the separation of the following four fractions: 1 (flavonoids, phenolics, glycosides, terpenoids, and steroids), 2 (alkaloids, anthraquinones, flavonoids, phenolics, glycosides, terpenoids, and steroids), 3 (anthraquinones, flavonoids, phenolics, glycosides, terpenoids, and steroids), and 4 (alkaloids, flavonoids, phenolics, glycosides, terpenoids, and steroids). The antiplasmodial activities of the fractions were tested against the 3D7 strain of Plasmodium falciparum with reported stronger activities for 1 (IC50: 0.097 ± 0.034 μg/mL) and 3 (IC50: 1.43 ± 0.072 μg/mL), and weaker activities for 2 (IC50: >100 μg/mL) and 4 (IC50: 37.09 ± 6.14 μg/mL). The full ESI-MS fingerprint of fractions 1, 2, 3, and 4 revealed the presence of 14, 24, 34, and 37 major molecular ions or compounds in each fraction, respectively.
... While the term "hemozoin" exclusively describes the heme species synthesized by parasites responsible for causing malaria (e.g. Plasmodium falciparum), synthetic hemozoin is termed β-hematin (Vanderesse et al. 2016). β-Hematin is a molecule that consists of two heme moieties joined by two ester linkages (chemical structure shown in Supplementary Fig. 1b) (Coronado et al. 2014;Vanderesse et al. 2016). ...
... Plasmodium falciparum), synthetic hemozoin is termed β-hematin (Vanderesse et al. 2016). β-Hematin is a molecule that consists of two heme moieties joined by two ester linkages (chemical structure shown in Supplementary Fig. 1b) (Coronado et al. 2014;Vanderesse et al. 2016). While one propionate side chain of one heme molecule is connected to the iron atom of the other molecule, the second side chain can generate intermolecular hydrogen bonds with other β-hematin molecules (Egan 2002;Jaramillo et al. 2009). ...
... While one propionate side chain of one heme molecule is connected to the iron atom of the other molecule, the second side chain can generate intermolecular hydrogen bonds with other β-hematin molecules (Egan 2002;Jaramillo et al. 2009). Thus, insoluble crystal structures are formed (Butykai et al. 2013;Coronado et al. 2014;Vanderesse et al. 2016), leading to the formation of the precipitate observed after NO-heme exposure to sunlight. In addition, β-hematin-specific IR bands in the range of 1664-1660 cm −1 as well as 1211-1207 cm −1 attributed to the ester linkages have been described in several previous studies (Slater et al. 1991;Egan et al. 1994;Basilico et al. 1997;Huy et al. 2007;Jaramillo et al. 2009;Coronado et al. 2014;Vanderesse et al. 2016). ...
Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.
Background: Malaria is responsible for a social and an economic burden in most low-income malaria-affected countries. Thus, newer antimalarials are needed to tackle morbidities and mortalities associated with the drug-resistant malarial strains. Haemoglobin digestion inside the food vacuole of malarial parasite would lead to producing redox-active and toxic-free heme. The detoxification process adopted by Plasmodium sp. would give rise to hemozoin (Hz) (beta-hematin) formation. Targeting the pathway of hemozoin formation is considered as a validated target for the discovery of newer antimalarials.
Objective: This study aims to collect detailed information about aspects of hemozoin (Hz) (beta-hematin) inhibitors.
Methods: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, ' hemozoin or beta-hematin' for almost the last 2 decades (2000-2021).
Results: This mini-review tries to summarize all the recent advancements made for the developments of synthetic, natural isolated phytoconstituents and plant extracts inhibiting the hemozoin (beta-hematin) formation.
Conclusion: thus, would act as promising antimalarial candidates in near future.
Keywords: Hemozoin, hemozoin inhibitors, Plant extracts, antimalarials, beta hematin, synthetic analogues
Neglected tropical diseases caused by protozoan parasites affect the life of millions of people worldwide, causing mortality, morbidity and high economic and social burden. The search for new drug targets and therapeutic strategies to fight these pathogens are necessary, since many current drugs have limited effects, cause severe side effects and their use has resulted in pathogen resistance. Heme (iron protoporphyrin IX) is a ubiquitous molecule important in many biological processes, including the homeostasis, growth and development of human pathogens such as trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) and Plasmodium spp. In this review, several chemotherapy approaches and strategies are discussed that target heme transport, catabolism, crystallization and hemeproteins.
