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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Cost-Effective Synthesis, Bioactivity and Cellular Uptake Study of Aminoglycosides with Antimicrobial and Connexin Hemichannel Inhibitory Activity

Subedi, Yagya P. 01 December 2019 (has links)
Amphiphilic kanamycin is one of the promising class of compounds for the treatment of fungal infections in plants and animal. Factor that lead to the restricting of compounds for commercialization includes, the higher cost of production and poor stability of the compound. However, the new lead, identified from the synthesis and biological testing, can be synthesized on a large scale with a cost comparable to commercial antifungals. The newly reported lead is stable at the acidic and basic conditions. Additionally, this compound has an excellent activity towards Candida auris, a multidrug-resistant superbug. Heart disease is the leading cause of death in the United States most of which are caused by cardiac ischemia and arrhythmias. Abnormal opening of Cx43 hemichannel can damage the heart muscles and lead to these conditions. A compound which can selectively inhibit the opening of Cx43 hemichannel may pave the way to reducing the mortality rate of heart disease. A selective inhibitor towards Cx43 hemichannel is explored from the synthesis and biological testing of kanamycin derivatives. The synthesis of the new inhibitor is scalable and cost-effective.
2

Synthesis and Biological Studies of Amphiphilic Compounds Derived from Saccharides and Aminoglycosides

Alfindee, Madher N. 01 August 2019 (has links)
Adjacent cells communicate through gap junctions (GJs). These GJs are formed by head to head docking of two hemichannels (HCs) from two adjacent cells. HCs are connexin hexamer proteins. Connexin mutation is the most frequent cause of childhood hearing loss. This hearing impairment affects 2 in every 2000 children. Inhibition of the HCs might be the key factor to treat such disorders. A library of amphiphilic kanamycins was synthesized to be tested as HC inhibitors. These compounds showed excellent inhibition activity in comparison with the parent compound (kanamycin A) with less toxicity. A library of monosaccharide esters with varying carbon chain lengths (acetyl (C2) to hexadecyl (C16)) were synthesized, characterized, and tested for bioactivity. Carbohydrate esters showed low toxicity while remaining active against bacteria and fungi. The compound 6-O-tetradecanoyl-D-mannopyranose (MAN014), a mannose ester with a fourteen-carbon chain, showed the greatest antibacterial and antifungal properties. A mode of action study was tested against Staphylococcus aureus (bacteria) and Fusarium graminearum (fungus) and found the compound perturbed the cell membrum.

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