resumo
New drug targets for the development of antimalarial drugs have emerged after the unveiling of the Plasmodium falciparum genome in 2002. Potential antimalarial drug targets can be broadly classified into three categories according to their function in the parasite's life cycle: (i) biosynthesis, (ii) membrane transport and signaling, and (iii) hemoglobin catabolism. The latter plays a key role, as inhibition of hemoglobin degradation impairs maturation of blood-stage malaria parasites, ultimately leading to remission or even cure of the most severe stage of the infection. Intraerythrocytic Plasmodia parasites have limited capacity to biosynthesize amino acids which are vital for their growth. Therefore, the parasites obtain those essential amino acids via degradation of host cell hemoglobin, making this a crucial process for parasite survival. Several plasmodial proteases are involved in hemoglobin catabolism, among which plasmepsins and falcipains are well-known examples. Hence, development of P. falciparum protease inhibitors is a promising approach to antimalarial chemotherapy, as highlighted by the present review which is focused on the Medicinal Chemistry research effort recorded in the past decade in this particular field.
palavras-chave
POTENTIAL ANTIMALARIAL AGENTS; EXCESS HEMOGLOBIN DIGESTION; M17 LEUCINE AMINOPEPTIDASE; PLASMEPSIN-II INHIBITORS; PEPTIDYL VINYL SULFONES; CYSTEINE PROTEASE; IN-VITRO; MALARIA PARASITES; ACTIVE-SITE; FARNESYLTRANSFERASE INHIBITORS
categoria
Biochemistry & Molecular Biology; Pharmacology & Pharmacy
autores
Perez, B; Teixeira, C; Gomes, JRB; Gomes, P
nossos autores
Cátia Teixeira
Bolseiro de pós-Doutoramento
José R. B. Gomes
Investigador Principalagradecimentos
We are grateful to Fundacao para a Ciencia e a Tecnologia (FCT, Portugal), FEDER and Programa COMPETE for the financial support through project PTDC/QUI-QUI/116 864/2010 and strategic projects PEst-C/QUI/UI0081/2011 and PEst-C/CTM/LA0011/2011. CT and JRBG thank FCT for the post-doctoral fellowship SFRH/BPD/62967/2009 and for Programa Ciencia 2007, respectively. BP thanks FCT for the doctoral grant SFRH/BD/86166/2012.