Evaluation of metalorganic complexes for their anti-mycobacterial properties in vitro for future tuberculosis therapy
(2024) KIMM01 20241Educational programmes, LTH
Department of Immunotechnology
- Abstract
- Tuberculosis is caused by Mycobacterium Tuberculosis, an airborne bacterium that impacts the lungs, affecting one third of the global population, and was declared a global health emergency by the WHO. Multi-drug resistant variations of the pathogen diminish decades of drug discovery, development, and research. This complex and multi-factorial challenge calls for new approaches in anti-microbial drug development. Here, a new approach using metal-based drug complexes has been developed and tested in vitro. Ten different Ruthenium-based organometallic complexes with variable halogenation patterns were investigated for their anti-mycobacterial properties through assessing bacterial viability, human macrophage cytotoxicity, synergistic... (More)
- Tuberculosis is caused by Mycobacterium Tuberculosis, an airborne bacterium that impacts the lungs, affecting one third of the global population, and was declared a global health emergency by the WHO. Multi-drug resistant variations of the pathogen diminish decades of drug discovery, development, and research. This complex and multi-factorial challenge calls for new approaches in anti-microbial drug development. Here, a new approach using metal-based drug complexes has been developed and tested in vitro. Ten different Ruthenium-based organometallic complexes with variable halogenation patterns were investigated for their anti-mycobacterial properties through assessing bacterial viability, human macrophage cytotoxicity, synergistic interactions, and intracellular assays. Changes in halogenation patterns, influencing pharmacokinetic profiles, revealed potency differences due to variations of reactivity due to halogen size, electronegativity, and lipophilicity. Minimal cytotoxicity could be observed at low or medium dosages and administration of the metalorganic complexes in combination with Isoniazid and Ethambutol leading to increased biological activity, which could be further verified and amplified intracellularly. To conclude, the evaluated Ruthenium complexes exhibited potential as possible future tuberculosis therapies and our results warrant further investigations. (Less)
- Popular Abstract
- A small but clever bacterium that has evolved to impact one third of the global population, with 10 million new infections and 1.3 million deaths annually, is no other than Mycobacterium tuberculosis (Mtb). This disease-causing microorganism is accountable for the prevailing Tuberculosis (TB) epidemic and the progression of multi-drug resistant Tuberculosis (MDR-TB). As advancements in TB treatment have been developed, new resistance strategies have emerged simultaneously, meaning that previously administered drugs have little or lower abilities to kill Mtb. This makes it indispensable to continue exploring new drug molecules in the hope of finding a way to finally outsmart this ancient companion.
Our immune system tries its hardest to... (More) - A small but clever bacterium that has evolved to impact one third of the global population, with 10 million new infections and 1.3 million deaths annually, is no other than Mycobacterium tuberculosis (Mtb). This disease-causing microorganism is accountable for the prevailing Tuberculosis (TB) epidemic and the progression of multi-drug resistant Tuberculosis (MDR-TB). As advancements in TB treatment have been developed, new resistance strategies have emerged simultaneously, meaning that previously administered drugs have little or lower abilities to kill Mtb. This makes it indispensable to continue exploring new drug molecules in the hope of finding a way to finally outsmart this ancient companion.
Our immune system tries its hardest to fight any foreign invaders. Nevertheless, if infection takes place, this can take different manifestations as Mtb managed to enter the human body by airborne transmission. It can progress into active TB for which the patient experiences symptoms, such as coughs, possibly with blood sputum, fever, chills, chest pain or fatigue. However, the bacteria can also abide and reside within the human body without making itself known of its presence. To be effective, anti-TB drugs therefore need to exploit different strategies to provide treatment against Mtb in different physiological states. This is further complicated by the development of drug resistance, which calls for new ideas on how to treat this disease. In this thesis, a new approach of drug design was tested, namely so-called metalorganic complexes, i.e. chemical structures which enclose a metal ion, here Ruthenium. In addition, the molecule was subjected to small structural changes that lead to different interaction abilities with the bacteria, which were systematically tested.
By using different types of assays, the effect of these structural modifications of organometallic molecules could be evaluated in terms of efficacy of inhibiting bacteria growth, toxicity towards human cells and interactions with conventional anti-TB drugs. This study showed that the tested complexes possess the capacity to eliminate Mtb at concentrations of acceptable cell toxicity. In conclusion, the idea of using metal-based drug complexes provides an interesting and new research strategy that could potentially be further investigated in the journey towards new anti-tubercular drugs to improve patient treatment, offering hope for a brighter future in the fight against the white plague. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9164191
- author
- Abbrederis, Nathalie Maria LU
- supervisor
- organization
- course
- KIMM01 20241
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Tuberculosis, metalorganic complexes, BCG, anti-mycobacterial properties
- language
- English
- id
- 9164191
- date added to LUP
- 2024-06-18 10:42:30
- date last changed
- 2024-06-18 10:42:30
@misc{9164191,
abstract = {{Tuberculosis is caused by Mycobacterium Tuberculosis, an airborne bacterium that impacts the lungs, affecting one third of the global population, and was declared a global health emergency by the WHO. Multi-drug resistant variations of the pathogen diminish decades of drug discovery, development, and research. This complex and multi-factorial challenge calls for new approaches in anti-microbial drug development. Here, a new approach using metal-based drug complexes has been developed and tested in vitro. Ten different Ruthenium-based organometallic complexes with variable halogenation patterns were investigated for their anti-mycobacterial properties through assessing bacterial viability, human macrophage cytotoxicity, synergistic interactions, and intracellular assays. Changes in halogenation patterns, influencing pharmacokinetic profiles, revealed potency differences due to variations of reactivity due to halogen size, electronegativity, and lipophilicity. Minimal cytotoxicity could be observed at low or medium dosages and administration of the metalorganic complexes in combination with Isoniazid and Ethambutol leading to increased biological activity, which could be further verified and amplified intracellularly. To conclude, the evaluated Ruthenium complexes exhibited potential as possible future tuberculosis therapies and our results warrant further investigations.}},
author = {{Abbrederis, Nathalie Maria}},
language = {{eng}},
note = {{Student Paper}},
title = {{Evaluation of metalorganic complexes for their anti-mycobacterial properties in vitro for future tuberculosis therapy}},
year = {{2024}},
}