{"id":50302,"date":"2014-12-10T00:00:00","date_gmt":"2014-12-09T23:00:00","guid":{"rendered":"http:\/\/www.pcb.ub.edu\/analogues-of-a-natural-product-are-drug-candidates-against-malaria\/"},"modified":"2014-12-10T00:00:00","modified_gmt":"2014-12-09T23:00:00","slug":"analogues-of-a-natural-product-are-drug-candidates-against-malaria","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/analogues-of-a-natural-product-are-drug-candidates-against-malaria\/","title":{"rendered":"Analogues of a natural product are drug candidates against malaria"},"content":{"rendered":"

Malaria is one of the most serious health problems worldwide, registering 200 million clinical cases and more than 600,000 attributable deaths per year, according to information from the World Health Organization in 2013. Given the emerging resistance to the standard treatment most widely used throughout the world, which is based on artemisinin and its analogs, there is a need for new antimalarial compounds.<\/p>\n

In this regard, scientists headed by\u00a0Llu\u00eds Ribas de Pouplana,\u00a0ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona), report on a new family of molecules and a new system of action to combat the parasite\u00a0Plasmodium,<\/em>\u00a0causal agent of malaria. Specifically, they describe two derivatives of borrelidin that completely remove the parasite load from mice and confer immunological memory to fight future infections. The latter property is an added value that is not shared by current antimalarial drugs. The results are published in the journal\u00a0Proceedings of the National Academy of Sciences<\/em>\u00a0(PNAS).<\/p>\n

“We have found that the chemical space of borrelidin offers the opportunity to find very strong and efficient antimalarial drugs. We must now study the action and pharmacological properties of these compounds in order to pave the way for their development as drugs. That is to say, we have to explain why they show low toxicity in human cells and understand how they induce immunological memory,” states\u00a0Llu\u00eds Ribas.<\/p>\n

Borrelidin: a “new” agent against malaria<\/strong><\/p>\n

Borrelia is the bacteria that produces borrelidin, a toxic molecule for human cells. However, for several years, hundreds of analogues of this compound\u2014small variations made in the lab\u2014have been studied for use in cancer and heart disease treatment. The IRB Barcelona scientists performed an exhaustive analysis of the analogues and identified two\u2014BC196 and BC220\u2014that are useful for combating\u00a0Plasmodium<\/em>. The compounds show low toxicity in human cells\u00a0in vitro<\/em>\u00a0and a high efficiency at clearing the parasites both from cells\u00a0in vitro<\/em>\u00a0as well as from animals. “The efficiency of these two compounds and the doses to give to mice are comprable and even better than those of chloroquine, a compound that has been used to treat malaria for 100 years and that is no longer used because of emerging resistance worldwide,” explains\u00a0Ribas.<\/p>\n

Objective: to attack the parasite in all phases of the infection<\/strong><\/p>\n

The new molecules act on the protein production machinery of the parasite and they are therefore efficient in all phases of parasite infection in humans. With respect to the specific mechanism of action, the compounds based on borrelidin inhibit one of the 20 tRNA synthetases of the parasite, key molecules for the correct production of the proteins required for growth, replication and infection.<\/p>\n

“The synthetases are crucial for the parasite both when multiplying rapidly in the liver and when infecting red blood cells,” explains\u00a0Ribas,\u00a0head of the\u00a0Gene Translation Lab<\/a>\u00a0at IRB and expert in this fundamental process of life. “Because the compounds attack a general component of the protein production machinery, they are of considerable interest because drugs that act in all the stages of infection are also better for the prevention of the disease”.<\/p>\n

The findings are part of the final results of the European project\u00a0Mephitis,<\/em>\u00a0coordinated by\u00a0Ribas, which aims to increase the currently limited number of compounds available to tackle malaria.<\/p>\n

“It is most gratifying to end\u00a0Mephitis<\/em>\u00a0with a significant contribution to the pipeline of antimalarial compounds. We will see how far they get, but right now we have a new target and new molecules that work very well in the models tested,” concludes the scientist.<\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers at IRB Barcelona<\/a> identify a family of efficient and selective molecules to combat the parasite\u00a0Plasmodium, causal agent of malaria.\u00a0Two analogues of borrelidin were found to cure 100% of infected mice and produce immunological memory in these animals, a property not previously observed in an antimalarial drug.\u00a0Growing resistance to current treatment for malaria increases the need for new drug candidates.\u00a0The results are published in the PNAS,\u00a0Proceedings of the National Academy of Sciences\u00a0(doi:10.1073\/pnas.1405994111<\/a>).\u00a0<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"class_list":["post-50302","post","type-post","status-publish","format-standard","category-uncategorized"],"acf":[],"yoast_head":"\nAnalogues of a natural product are drug candidates against malaria - 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