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Peroxisomes01:24

Peroxisomes

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Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
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α-Alkylation of Ketones via Enolate Ions01:10

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Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...
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Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids02:04

Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids

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Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
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Acid-Catalyzed Ring-Opening of Epoxides02:24

Acid-Catalyzed Ring-Opening of Epoxides

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Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
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Base-Catalyzed Ring-Opening of Epoxides02:26

Base-Catalyzed Ring-Opening of Epoxides

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Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
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Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Natural endoperoxides as promising anti-leishmanials.

Deblina Sarkar1, Lianet Monzote2, Lars Gille3

  • 1Department of Pharmacology, Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata-700 020, W.B, India.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|May 7, 2024
PubMed
Summary

Natural endoperoxides like artemisinin show promise against leishmaniasis by exploiting parasite weaknesses. Further research into these compounds could lead to new treatments for this neglected tropical disease.

Keywords:
Anti-leishmanialArtemisininAscaridoleEndoperoxidesOxidative stressReactive oxygen species (ROS)

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Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Drug Discovery

Background:

  • Endoperoxides, inspired by artemisinin, are explored for anti-parasitic properties.
  • Leishmaniasis treatment faces challenges due to drug resistance and toxicity.
  • Leishmania parasites have a weak antioxidant defense, making them susceptible to oxidative stress.

Purpose of the Study:

  • To review natural endoperoxides' anti-leishmanial efficacy.
  • To understand the mechanisms of action for these compounds.

Main Methods:

  • A comprehensive literature review of approximately 110 articles.
  • Searches conducted across major scientific databases (PubMed, Web of Science, Google Scholar).

Main Results:

  • Artemisinin and ascaridole show potential as anti-leishmanial agents.
  • Endoperoxides induce redox imbalance and inhibit glycolytic functions in Leishmania.
  • Generated free radicals damage Leishmania macromolecules, leading to apoptosis.

Conclusions:

  • Natural endoperoxides represent a promising class of anti-leishmanial agents.
  • Artemisinin and ascaridole are key examples with demonstrated efficacy.
  • Further investigation into novel natural endoperoxides is warranted for therapeutic development.