Identification of In-Vitro effects of synthesized heterocycles against Balamuthia Mandrillaris and Naegleria Fowleri

Mohammad, Mungroo Ridwane (2020) Identification of In-Vitro effects of synthesized heterocycles against Balamuthia Mandrillaris and Naegleria Fowleri. Masters thesis, Sunway University.

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Abstract

Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis, with mortality rates of over 95%, indicating lack of effective treatments. Quinazolinones, benzimidazole, indole, indazole, tetrazole and thiazole possess a wide spectrum of biological properties and it was recently reported that nanoparticles-based materials have improved in vitro activity against brain-eating amoebae. In this study, 34 novel quinazolinones were synthesized along with benzimidazole, indole, indazole, tetrazole and thiazole compounds, containing varying moieties. These molecules were tested for the first time against N. fowleri and B. mandrillaris. We also conjugated quinazolinones and heterocyclic scaffolds with silver nanoparticles to increase their amoebicidal activities. Synthesized compounds were tested for their amoebicidal and amoebistatic properties against B. mandrillaris and N. fowleri. The results revealed that quinazolinones decreased the number of viable B. mandrillaris and N. fowleri cells by up to 89% and 77%, respectively. Also, quinazolinones inhibited growth of B. mandrillaris and N. fowleri by up to 77% and 47%, respectively. The heterocyclic scaffolds showed up to 65% and 72% amoebicidal activity against B. mandrillaris and N. fowleri, respectively, and expressed up to 73% and 75% amoebistatic effects, respectively. We also showed that activities of the compounds were successfully enhanced by up to 65% and 71%, against N. fowleri and B. mandrillaris, respectively, due to conjugation with silver nanoparticles. Given the challenges in developing new drugs, enhancing anti-amoebic effects of compounds using nanotechnology is a worthwhile avenue with promise in improving treatment of brain-eating amoebae infections.

Item Type: Thesis (Masters)
Uncontrolled Keywords: In-Vitro; synthesized heterocycles; Balamuthia Mandrillaris; Naegleria Fowleri; protist; pathogens; pathogenic microorganisms; central nervous system; brain-eating amoebae.
Subjects: Q Science > QR Microbiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Sunway University > School of Engineering and Technology [formerly School of Science and Technology until 2020] > Dept. Biological Sciences moved to SMLS wef 2021
Depositing User: Ms Yong Yee Chan
Date Deposited: 05 Oct 2023 02:54
Last Modified: 05 Oct 2023 02:54
URI: http://eprints.sunway.edu.my/id/eprint/2428

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