DESTAQUE

Os complexos metálicos de Johannes Karges abrem uma nova porta para os tratamentos quimioterápicos

Jovem estrela da química alemã fará conferência na 48ª RASBQ

As citações às publicações do químico alemão Johannes Karges (Ruhr University Bochum) dispararam nos últimos anos, de 310 em 2020 para 1388, em 2024. Sua pesquisa com complexos metálicos catalisadores com potencial farmacológico contra o câncer está abrindo novas perspectivas para o tratamento quimioterápico, e ele aceitou o convite da divisão de Química Inorgânica para ministrar uma conferência na 48a RASBQ. "Eu tenho a sorte de ter uma equipe excelente de pesquisadores jovens, talentosos e motivados, e colaboradores de alto nível", declarou o pesquisador ao Boletim Eletrônico SBQ.

Johannes Karges (Ruhr University Bochum): "Tenho longa admiração pela herança cultural e científica do Brasil e espero conhecer melhor como a pesquisa química é conduzida no país"

Nascido em 1992, o Professor Karges foi pós-doc no laboratório de Seth Cohen, que veio à RASBQ no ano passado, e trabalhou na equipe de Gilles Gasset, que participou da RASBQ em 2023. "Sua vinda é um complemento natural neste tema importante que é o potencial farmacológico de complexos metálicos", explica o Professor Luiz Antônio Sodré Costa (UFJF), diretor da divisão de Inorgânica.

Em sua conferência, Karges vai descrever duas estratégias que envolvem o design, a síntese, e a realização de testes biológicos de complexos metálicos que têm mecanismos de ação inéditos. A primeira trata de complexos metálicos que convertem a glutationa em dissulfeto de glutationa, e assim enfraquecem o sistema de defesa das células cancerígenas, tornando-as extremamente vulneráveis ao estresse oxidativo.

Prof. Luiz Antonio Sodré Costa (UFJF), com Karges e a Dra. Masha Babak (City University of Hong Kong) e o doutorando Patrick Bokolo, durante a Gordon Conference in Medicine de 2024: "Depois de termos trazido Seth Cohen e Gilles Gasset, sua vinda é um complemento natural neste tema importante que é o potencial farmacológico de complexos metálicos"

Na segunda estratégia, complexos metálicos são introduzidos como fotocatalisadores, capazes de gerar espécies reativas de oxigênio por meio da ativação de luz para direcionamento tumoral altamente preciso. Da mesma forma atuam diretamente nas células tumorais. O professor Bernardo Iglesias (UFSM), vice-diretor da Divisão de Química Inorgânica, explica que a terapia fotodinâmica tem se mostrado uma alternativa promissora no combate de enfermidades. “Ela tem sua ação baseada em três pontos principais, sendo eles: o uso de sensibilizadores, luz e molécula de oxigênio, para induzir dano celular. Caracteriza-se por ser um método minimamente invasivo e seletivo para tumores, além de apresentar diminuição dos efeitos adversos ao paciente.”
O professor Karges concedeu a seguinte entrevista ao B.E., em que aborda aspectos de sua pesquisa, detalha a bela infra-estrutura que seu grupo de pesquisa conta, com um cluster computacional de alta performance para realizar predições, o laboratório totalmente equipado para síntese e caracterização, e um laboratório de biologia, em que seu grupo conduz os primeiros testes com as células tumorais. Ele também fala sobre sua parceria com a indústria farmacêutica e as expectativas para esta que será sua primeira vinda ao Brasil.

In what stage are the two strategies you describe in the abstract of your presentation?
My research group specializes in medicinal inorganic chemistry, focusing on overcoming the limitations of currently clinically applied drugs with metal-based agents. In my presentation at the Brazilian Chemical Society conference, I'll discuss one aspect of our research on using metal complexes as catalysts to target cancer cells. In the first strategy, I'll discuss how we use these complexes to convert glutathione, a key part of the cell’s defense system, into its oxidized form glutathione disulfide. This conversion leads to the buildup of reactive oxygen species, overwhelming the cancer cell’s defenses and ultimately causing cell death. Importantly, this approach works in hypoxic conditions (low oxygen), which is a limitation for most anticancer drugs. We’ve recently published two important papers on this: Angew. Chem. Int. Ed. 2024, e202412585 and Nature Commun. 2024, 15, 9405.
The second strategy focuses on improving the selectivity of our treatments by activating our drug candidates using light. The compounds are non-toxic in the dark but, when exposed to light at the target site, they generate reactive oxygen species that kill the cancer cells. This method allows for precise, targeted therapy. We've also published recent papers on this strategy: Nature Commun. 2023, 14, 5350 and Chem. Commun. 2024, 60, 10724-10727.

Could you describe your group: how many people are involved and what kind of infrastructure you have?
We are fortunate to have excellent research infrastructure at Ruhr University in Germany. In my lab, we are equipped with a high-performance computational cluster, which allows us to predict the properties of new molecules and design compounds with tailored properties. This enables us to work efficiently and develop clear strategies for creating new and improved drug candidates (however, we are not theoretical chemists and use easy theoretical methods).
In addition to the computational tools, we have a fully equipped chemical lab where we synthesize and characterize these molecules. Once synthesized, we move on to biological testing in our dedicated cell culture lab, where we evaluate the therapeutic efficiency of our compounds in cancer cells. This includes mechanistic studies, such as determining how the compound enters the cells, where it accumulates, and what type of cell death it induces. Successful compounds are then tested in more complex three-dimensional cellular models, such as multicellular tumor spheroids (Microtumors), to further investigate their biological effects.
This integrated approach—combining computational design, chemical synthesis, and biological testing in cancer cells and tumor spheroids—enables us to conduct comprehensive research all within my lab. If a compound shows promise, we then seek collaborations to test its effects in animal models.
As for the composition of my group, it is dynamic and constantly evolving. Currently, we have seven students in the lab. A key focus for me is maintaining a diverse team, with approximately half of our members coming from outside of Germany. For instance, one of my PhD students, who is in his second year of his PhD is from Ecuador, which adds to the global perspective and collaboration in our research.

How does the big pharma industry view your research? Do you have any partnerships or prospects with the industry?
In a separate research direction focused on the use of platinum complexes for anticancer therapy (which I won't be covering in my presentation), we are already collaborating with the pharmaceutical industry. While this partnership is still in its early stages, we are optimistic about its potential and hopeful that it will progress successfully in the future.

This will be your first visit to Brazil. What are your expectations in terms of the country, the event, and meeting the Brazilian chemical community?
I am extremely grateful for the kind invitation to contribute to the Brazilian Chemical Society conference. This event is an exceptional opportunity to engage with the latest developments in the field and witness the innovative research being conducted in Brazil. It’s truly an honor to be part of such a prestigious gathering, where cutting-edge science and future directions in chemistry will be discussed.
As this will be my first visit to Brazil, I am especially excited to explore the country, immerse myself in its vibrant culture, and experience the warmth and hospitality of its people. I look forward to seeing firsthand how research is approached and conducted in Brazil. The country's rich cultural and scientific heritage is something I have long admired, and I’m eager to gain deeper insight into the scientific landscape here.
Regarding the conference itself, I’m thrilled to have the chance to exchange ideas with fellow researchers and to share our work on metal-based agents in medicinal chemistry. The event presents a unique platform for learning about the innovative work happening in Brazil, which is particularly exciting given the country’s growing role in global scientific advancement. I believe this will be an excellent opportunity to foster collaboration, explore new perspectives, and establish valuable connections that will help broaden our global network within the chemical community.

Saiba mais: www.kargesgroup.ruhr-uni-bochum.de

Texto: Mario Henrique Viana (Assessoria de Imprensa da SBQ)