The article of Olomouc chemists, printed at the end of last year by the prestigious Journal of Organic Chemistry, has reached the elite selection in Synfacts magazine. The editors usually include articles focused on organic synthesis, with assumed major scientific impact and application in pharmaceutical research. Scientists have focused on a method for developing substances that might be effective in combating Leishmania parasites.
Authors of the article Jiří Pospíšil, Daniela Konrádová and David Jean-Yves Denis Bon from the Laboratory of Growth Regulators and Olomouc worksite of Institute of Experimental Botany of the Academy of Sciences of the Czech Republic, part of the Center of the Region Haná for Biotechnological and Agricultural Research and the Department of Organic Chemistry of the Faculty of Science, have been devoted to studying natural substances. This time, they focused on phenylpropanoid-type substances that are known to exhibit some biological activity. Because scientists have long been looking for an effective way to fight the leishmania parasite, they have started with kava extract, which was used by shamans in South America to treat illnesses.
“Our goal was not to develop a cure but to understand the principle of how to destroy the parasite without harming the host organism. So we have tried to develop a method for developing substances that are structurally similar to our kava extract, but have a slightly different architecture. We do not know the precise mechanism of the effect of the substance, so we actually do not know what exactly we are aiming for. That is why we tried to prepare substances based on the same molecule, which we transform in two or three steps to the entire library of structurally diverse substances. This is a so-called diversity-oriented synthesis, which has been applied extensively to search for new biologically active substances since its inception in the first decade of our century. By this approach we have probably intrigued the evaluators,” explained Jiří Pospíšil, first author of the article.
Leishmania is a genus of parasitic protozoa that causes various forms of disease called leishmaniasis. Among vertebrates, including humans, they are spread by blood-sucking insects. The parasite affects immunity, internal organs or, for example, skin. It is common mainly in the Middle East, South America, India, Afghanistan and gradually penetrates into southern Europe. According to the World Health Organization, the parasite annually affects 350 million people.
“Our task was not to find a cure, but rather ‘helpers’ – new substances that would allow us to understand the mechanism of their effect. However, if it turns out that one of our substances is usable for further development, it would of course be great. So far, it has been kind of a probe. The research, however, continues and my Ph.D. student Daniela Konrádová has tested the efficiency of substances at Hebrew University in Professor Jaffe’s group directly on leishmani. It is one of the best laboratories in this field in the world,” added Pospíšil. The young researcher was supported by the UP Foundation.
The fact that the information on article 1- (Phenylsulfonyl) -3-oxabicyclo [3.1.0] hexan-2-one as a Building Block in Organic Synthesis penetrated into the December issue of Synfacts, is seen as a great success by Pospíšil, among other things a laureate of Alfred Bader Award for Organic Chemistry (the most prestigious award for young chemists under 35). “It cannot be taken for granted. I personally have achieved this for the first time in my life,” he added.