Prof. Bernd Plietker and his research group at the Chair of Organic Chemistry I at TUD have specifically developed a class of natural substances—polyprenylated polycyclic acylphloroglucinols (PPAP for short). Due to its properties, the resulting derivative PPAP53 is characterized by great potential for application in a medicinal chemistry context. In collaboration with several research institutions, such as the Universities of Ulm and Mainz, it has been shown that PPAP53 is very promising in the fight against multi-resistant tuberculosis and opens up new treatment perspectives for neurodegenerative diseases.
Tuberculosis (TB) is a prevalent infectious disease that affects millions of people each year. It was previously the leading cause of death from a single pathogen before the COVID-19 pandemic. Detecting TB early is challenging because the bacterium Mycobacterium tuberculosis (Mtb) can hide in human macrophages, which are part of the immune system. This makes it difficult for conventional diagnostic methods to detect the infection until the macrophages collapse, leading to “open tuberculosis.”
TB can be treated with common antibiotics, but the repeated exposure of Mtb to these drugs can result in the development of multidrug-resistant and extensively drug-resistant strains. This highlights the importance of finding alternative treatment options to combat this challenging disease.
A few years ago, Prof. Bernd Plietker made a promising new class of natural substance-based active compounds accessible by developing a short and parallelizable total synthesis: polyprenylated polycyclic acylphloroglucinols (PPAP for short). “Initial studies on the antimicrobial activity of the non-natural derivatives we developed already indicated that this class of molecules offers the potential for application in a medicinal chemistry context through interactions with membrane-associated proteins,” explains Bernd Plietker, who has held the Chair of Organic Chemistry I at TU Dresden since 2020.
Building on these initial results, he and his team, in cooperation with Prof. Steffen Stenger from Ulm University Hospital, have now been able to show that a specific PPAP, PPAP53, is able to activate human macrophages to fight resistant tuberculosis bacteria without being toxic to the macrophages themselves.
2023-12-11 20:41:03
Original from phys.org rnrn
