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Small molecules that target Malaria parasites
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A malária é uma doença causada pelo parasita do género Plasmodium, que se transmite pela picada do mosquito fêmea do género Anopheles. O parasita desenvolve-se inicialmente no fígado e depois no sangue, provocando uma infeção sistémica com febres altas, que se não for tratada progride para malária severa, com anemia e possivelmente morte. As espécies patogénicas para o homem são P. falciparum, P. vivax, P. malariae, P. ovale e P. knowlesi, sendo P. falciparum a mais grave e P. vivax a mais complicada de tratar, já que o parasita pode permanecer no fígado num estado de dormência até provocar uma recaída de malária meses ou anos mais tarde.
Desde a existência de malária que são procuradas formas de a tratar. Embora as recomendações de infusões de Qing Hao para o tratamento de malária sejam mais antigas, uma vez que datam do século I d.C., só a partir do século XVII se começou a tratar a malária com o primeiro fármaco conhecido para o seu tratamento, ainda hoje usado, a quinina. Uma vez conhecida a origem da malária e uma forma de a tratar, muita investigação foi feita para chegarmos ao controlo da doença que existe atualmente, assim como leque de fármacos que são apresentados nesta monografia. São eles as quinolinas (primaquina, atovaquona, cloroquina, amodiaquina, piperaquina, quinina, mefloquina e lumefantrina), os derivados da artemisinina (dihidroartemisinina, artesunato e artemeter), os antifolatos (proguanilo e pirimetamina) e os antibióticos (sulfadoxina, clindamicina e doxiciclina). Contudo, muitas resistências surgiram e continuam a surgir, ameaçando a delimitação geográfica e a taxa de mortalidade conseguidas nestes últimos anos e afastando o objetivo de erradicação.
Nesta monografia é apresentada uma pequena parte das investigações mais promissoras que têm sido feitas recentemente, de diferentes grupos químicos: 8-aminoquinolinas, imidazopirazinas, análogo do ácido hidroxâmico e pirazolamidas.
Malaria is a disease caused by parasites of the genus Plasmodium, transmitted by the mosquito bite from the female of the genus Anopheles. The parasite initially develops in the liver and then into the blood, causing a systemic infection with high fever, which if left untreated progress to severe malaria, with anaemia and possibly death. The pathogenic species for humans are P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi, P. falciparum being the most severe and P. vivax more complicated to handle, since the parasite can remain the liver in a dormant state to cause a malarial relapse months or years later. Since the existence of malaria that are sought ways to treat it. Although the recommendations of Qing Hao infusions for the treatment of malaria are older, as dating from the first century A.D., only after the seventeenth century it began to be treated with the first drug known to treat malaria, and still used, quinine. Once known the origin of malaria and a way to treat it, much research has been done to reach the control of the disease that currently exists, as well as the range of drugs that are presented in this monograph. They are quinolines (primaquine, atovaquone, chloroquine, amodiaquine, piperaquine, quinine, mefloquine and lumefantrine), derivatives of artemisinin (dihydroartemisinin, artesunate and artemether), antifolates (proguanil and pyrimethamine) and antibiotics (sulfadoxine, clindamycin and doxycycline). However, many resistances have emerged and continue to emerge, threatening the geofencing and the mortality rate achieved in recent years and moving away the goal of eradication. In this monograph is shown a small part of the most promising research that have been made recently in different chemical groups: 8-aminoquinolines, imidazopyrazines, hydroxamic acid analogues and pyrazoleamides.
Malaria is a disease caused by parasites of the genus Plasmodium, transmitted by the mosquito bite from the female of the genus Anopheles. The parasite initially develops in the liver and then into the blood, causing a systemic infection with high fever, which if left untreated progress to severe malaria, with anaemia and possibly death. The pathogenic species for humans are P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi, P. falciparum being the most severe and P. vivax more complicated to handle, since the parasite can remain the liver in a dormant state to cause a malarial relapse months or years later. Since the existence of malaria that are sought ways to treat it. Although the recommendations of Qing Hao infusions for the treatment of malaria are older, as dating from the first century A.D., only after the seventeenth century it began to be treated with the first drug known to treat malaria, and still used, quinine. Once known the origin of malaria and a way to treat it, much research has been done to reach the control of the disease that currently exists, as well as the range of drugs that are presented in this monograph. They are quinolines (primaquine, atovaquone, chloroquine, amodiaquine, piperaquine, quinine, mefloquine and lumefantrine), derivatives of artemisinin (dihydroartemisinin, artesunate and artemether), antifolates (proguanil and pyrimethamine) and antibiotics (sulfadoxine, clindamycin and doxycycline). However, many resistances have emerged and continue to emerge, threatening the geofencing and the mortality rate achieved in recent years and moving away the goal of eradication. In this monograph is shown a small part of the most promising research that have been made recently in different chemical groups: 8-aminoquinolines, imidazopyrazines, hydroxamic acid analogues and pyrazoleamides.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2016
Palavras-chave
Malária Plasmodium Fármacos antimaláricos Novos fármacos Novas moléculas Mestrado Integrado - 2016