impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

Parassitologia 50: 133-136, 2008
Old and new targets for innovative antimalarial compounds:
the different strategies of the Italian Malaria Network.
N. Basilico 1,3, E. Bosisio 2, F. Buelli 6, G. Campiani 3,4, M. Casagrande 5, F. Castelli 6,
P. Coghi 7, Y. Corbett 1, L. Cortelezzi 8, S. D’Alessandro 1, M. Dell’Agli 2, F. Esposito 9,
C. Fattorusso 10, E. Fattorusso 3,10, S. Finaurini 1, G.V. Galli 2, S. Gemma 3,4, A.
Habluetzel 9, L. Lucantoni 9, S. Melato 7, D. Monti 3,7, P. Olliaro 11, F. Omodeo-Salè 8,
S. Parapini 1, M. Persico 10, M. Rizzi 12, S. Romeo 5, F. Rossi 12, C. Rusconi 5, A.
Sparatore 5, O. Taglialatela Scafati 10, E. van den Bogaart 1, D. Taramelli 1,3, N.
Vaiana 5 , S. Yerbanga 9
1 Dipartimento Salute Pubblica-Microbiologia-Virologia; 2 Dipartimento Scienze Farmacologiche, Università di Milano; 3 Centro
di Ricerca Interuniversitario NatSynDrugs; 4 Dipartimento Farmaco Chimico Tecnologico, Università di Siena; 5 Ist. Chimica
Farmaceutica e Tossicologica, Università di Milano; 6 Istituto di Malattie Infettive e Tropicali, Università di Brescia; 7 ISTM –
CNR Milano; 8 Istituto di Fisiologia Generale e Chimica Biologica “G Esposito,Università di Milano; 9 Dipartimento di
Medicina Sperimentale e Sanità Pubblica, Università di Camerino; 10 Dipartimento di Chimica delle Sostanze Naturali,
Universita’ di Napoli “Federico II”; 11 UNICEF-UNDP-World Bank-WHO-TDR, Geneva, CH; 12 DiSCAFF, Università del
Piemonte Orientale “A. Avogadro”.
Abstract. Clinical treatment-failures to affordable drugs encouraged new investigation for discovery and
development of new prophylactic and therapeutic interventions against malaria. The Drug Discovery Cluster
(DDcl) of the Italian Malaria Network gathers several highly integrated and complementary laboratories from
different Italian Institutions to identify, synthesise, screen in vitro and in vivo new antimalarial molecules
directed against the intraerythrocytic stage of P. falciparum parasites and/or with transmission blocking
activity to select lead compounds for further development. Complementary research activities, both in vitro
and in the clinics, aim at investigating the pathogenetic mechanisms of severe malaria anaemia and the different
manifestations of the disease in malaria-HIV co-infected patients to identify new therapies and
improve survival.
Key words: Malaria, P. falciparum, antimalarial drugs, trasmission blocking agents, severe anaemia.
Clinical treatment-failures to affordable drugs contributed
to the global increase in the number of deaths
arising from malaria infection (Breman, Alilio et al.
2007).There is an absolute requirement for new prophylactic
and therapeutic interventions at all levels, as
acknowledged by the G8 summits in 2006 and 2007,
and by the new Strategy of TDR-WHO, that proposes
“to foster innovation for product discovery and development
as part of an effective global research effort on
infectious diseases of poverty in which disease endemic
countries play a pivotal role”(WHO-TDR 2007). In
particular, the clinical and epidemiological features of
falciparum malaria require new approaches targeting
the parasite, its transmission and the most severe
malaria complication, namely cerebral malaria or
severe anaemia. Novel drugs should be cheap and safe,
free from cross-resistance with existing ones and be
Correspondence: Donatella Taramelli
Dipartimento di Sanità Pubblica-Microbiologia-Virologia,
Università di Milano, Via Pascal 36, 20133 Milano, Italy
Tel: +39 02 50315071; fax: +39 02 505068;
e-mail: donatella.taramelli@unimi.it
adapted to use in combination chemotherapy. New
combinations should include transmission-blocking
compounds.
On this background, the principal aim of the Drug
Discovery Cluster (DDcl) of the Italian Malaria
Network is to identify, synthesise, screen in vitro and in
vivo new antimalarial molecules directed against the
intraerythrocytic stage of P. falciparum parasites and/or
with transmission blocking activity to select lead compounds.
Optimization of leads through iterative medicinal
chemistry and pharmacological profiling will allow
the selection of drug candidates for preclinical tests.
Adjunctive therapies are under study for those patients,
usually children, that develop severe anaemia.
To achieve these objectives DDcl has been organised in
the last few years as a multidisciplinary network that
gathers several highly integrated and complementary
laboratories and clinicians from different Italian
Universities and from the CNR. DDcl has the expertise
for isolation and synthesis of new compounds (chemical
labs), for in vitro and in vivo screening for efficacy
(biological labs), for the characterization of the molecular
targets and mechanism of action, for optimization
of lead compounds through a “molecular modelling”