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Journal ArticleDOI

7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani.

TL;DR: In this article, the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani were analyzed.
About: This article is published in Nanomedicine: Nanotechnology, Biology and Medicine.The article was published on 2021-08-16. It has received 5 citations till now.
Citations
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Journal ArticleDOI
TL;DR: In this article, the role of physicochemical properties of a nanoscale delivery system is discussed and different ways of nano-formulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite.

16 citations

Journal ArticleDOI
TL;DR: A review of different forms of leishmaniasis disease and their current treatment options with limitations is presented in this paper , where nanoparticles with different size, shape and structure for drug delivery against Leishmania donovani are discussed.
Abstract: Visceral leishmaniasis (VL) is the most lethal of all leishmaniasis diseasesand the second most common parasiticdisease after malaria and,still, categorized as a neglected tropical disease (NTD). According to the latest WHO study, >20 Leishmania species spread 0.7–1.0 million new cases of leishmaniasis each year. VL is caused by the genus, Leishmania donovani (LD), which affects between 50,000 and 90,000 people worldwide each year. Lack of new drug development, increasing drug resistance, toxicity and high cost even with the first line of treatmentof Amphotericin B (AmB), demands new formulation for treatment of VLFurther the lack of a vaccine, allowedthe researchers to develop nanofomulation-based AmB for improved delivery. The limitation of AmB is its kidney and liver toxicity which forced the development of costly liposomal AmB (AmBisome) nanoformulation. Success of AmBisome have inspired and attracted a wide range of AmB nanoformulations ranging from polymeric, solid lipid, liposomal/micellar, metallic, macrophage receptor-targetednanoparticles (NP) and even with sophisticated carbon/quantum dot-based AmBnano delivery systems. Notably, NP-based AmB delivery has shown increased efficacy due to increased uptake, on-target delivery and synergistic impact of NP and AmB. In this review, we have discussed the different forms of leishmaniasis disease and their current treatment options with limitations. The discovery, mechanism of action of AmB, clinical status of AmB and improvement with AmBisome over fungizone (AmB-deoxycholate)for VL treatment was further discussed. At last, the development of various AmB nanoformulation was discussed along with its adavantages over traditional chemotherapy-based delivery. Graphical Abstract The nanoparticles with different size, shape and structure for drug delivery against Leishmania donovani.

2 citations

Journal ArticleDOI
TL;DR: In this article, the physicochemical properties of nanocarriers and the possible mechanisms of covalent and non-covalent interaction between nanoparticles (NPs) and drugs are studied.
Abstract: Flavones such as 7,8-dihydroxyflavone (tropoflavin), 5,6,7-trihydroxyflavone (baicalein), 3′,4′,5,6-tetrahydroxyflavone (luteolin), 3,3′,4′,5,5′,7-hexahydroxyflavone (myricetin), 4′,5,7-trihydroxyflavone (apigenin), and 5,7-dihydroxyflavone (chrysin) are important both for their presence in natural products and for their pharmacological applications. However, due to their chemical characteristics and their metabolic processes, they have low solubility and low bioavailability. Knowledge about the physicochemical properties of nanocarriers and the possible mechanisms of covalent and non-covalent interaction between nanoparticles (NPs) and drugs is essential for the design of nanocarriers to improve the bioavailability of molecules with pharmacological potential, such as tropoflavin, baicalein, luteolin, myricetin, apigenin, and chrysin. The parameters of characterization of some NPs of these flavones, such as size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and % release/time, utilized in biomedical applications and the covalent and non-covalent interactions existing between the polymeric NPs and the drug were analyzed. Similarly, the presence of functional groups in the functionalized carbon nanotubes (CNTs), as well as the effect of pH on the % adsorption of flavonoids on functionalized multi-walled carbon nanotubes (MWCNT-COOH), were analyzed. Non-covalent interaction mechanisms between polymeric NPs and flavones, and covalent interaction mechanisms that could exist between the NPs and the amino and hydroxyl functional groups, are proposed.

1 citations

Book ChapterDOI
13 Apr 2022
TL;DR: In this article , the authors have discussed potential therapeutic targets of antileishmanial drug discovery such as pteridine reductase (PTR1), trypanothione synthetase (TryS), IU-nucleoside hydrolase, and topoisomerases, enzymes and their inhibitors reported in the literature.
Abstract: The leishmaniases are a group of diseases caused by protozoan parasites—Leishmania sp. Leishmaniasis is classified among the 20 neglected diseases by WHO. Although the disease has been known for more than 120 years, the number of drugs used for the treatment is still limited to 5–6. The first-line drugs against leishmaniasis are pentavalent antimonials, which were introduced to the treatment 70 years ago—despite all their side effects. Molecular targets are becoming increasingly important for efficacy and selectivity in postgenomic drug research studies. In this chapter, we have discussed potential therapeutic targets of antileishmanial drug discovery such as pteridine reductase (PTR1), trypanothione reductase (TR), N-myristoyltransferase (NMT), trypanothione synthetase (TryS), IU-nucleoside hydrolase, and topoisomerases, enzymes and their inhibitors reported in the literature.
Journal ArticleDOI
TL;DR: In this paper , the authors evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL).
Abstract: Abstract We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8–C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.
References
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Journal ArticleDOI
TL;DR: Current trends of research and development activities on flavonoid relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits and future research directions are discussed.
Abstract: Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.

2,879 citations

Journal ArticleDOI
TL;DR: The methods of making nanoparticles using plant extracts are reviewed, methods of particle characterization are reviewed and potential applications of the particles in medicine are discussed.

1,706 citations

Journal ArticleDOI
TL;DR: Millefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphoteric in B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies.
Abstract: Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.

1,463 citations

Journal ArticleDOI
TL;DR: This review summarized the fundamental processes and mechanisms of “green” synthesis approaches, especially for metal and metal oxide nanoparticles using natural extracts and explored the role of biological components, essential phytochemicals (e.g., flavonoids, alkaloids, terpenoids, amides, and aldehydes) as reducing agents and solvent systems.
Abstract: In materials science, “green” synthesis has gained extensive attention as a reliable, sustainable, and eco-friendly protocol for synthesizing a wide range of materials/nanomaterials including metal/metal oxides nanomaterials, hybrid materials, and bioinspired materials. As such, green synthesis is regarded as an important tool to reduce the destructive effects associated with the traditional methods of synthesis for nanoparticles commonly utilized in laboratory and industry. In this review, we summarized the fundamental processes and mechanisms of “green” synthesis approaches, especially for metal and metal oxide [e.g., gold (Au), silver (Ag), copper oxide (CuO), and zinc oxide (ZnO)] nanoparticles using natural extracts. Importantly, we explored the role of biological components, essential phytochemicals (e.g., flavonoids, alkaloids, terpenoids, amides, and aldehydes) as reducing agents and solvent systems. The stability/toxicity of nanoparticles and the associated surface engineering techniques for achieving biocompatibility are also discussed. Finally, we covered applications of such synthesized products to environmental remediation in terms of antimicrobial activity, catalytic activity, removal of pollutants dyes, and heavy metal ion sensing.

1,175 citations

Journal ArticleDOI
TL;DR: In this paper, a comprehensive review of the synthesis and characterization methods used for green synthesis of ZnO NPs using different biological sources is presented, including plants, fungus, bacteria, and algae.

669 citations