Special Issue "Neglected Diseases: Medicinal Chemistry and Natural Product Chemistry"

Guest Editor
Dr. Ronan Batista
Departamento de Estudos Básicos e Instrumentais, Universidade Estadual do Sudoeste da Bahia, BR 415, Km 03, s/nº, 45.700-000 Itapetinga – BA, Brazil
E-mail:

Aims:
This special issue will focus on the top-ten neglected diseases as defined by the World Health Organization:

• Human African Trypanosomiasis (HAT or sleeping sickness)
• Chagas disease
• Dengue
• Leishmaniasis
• Leprosy
• Lymphatic filariasis (Elephantiasis)
• Malaria
• Onchocerciasis (River Blindness)
• Schistosomiasis ( Bilharzia)
• Tuberculosis

Tropical medicine, infectious diseases, medicinal chemistry, natural products chemistry

Manuscript ID: molecules-negdis-20081029-br-de Castro
Tentative title: The Microbicidal Activity of Naphthoquinones: A Review
Authors: Antônio Ventura Pinto (NPPN, UFRJ) and Solange Lisboa de Castro* (IOC, Fiocruz)
E-mail: solange@ioc.fiocruz.br
Abstract: Naphthoquinones are compounds present in different families of plants; their molecular structures endow them with redox properties, being involved in different biological oxidative processes. In folk medicine, especially among Indian populations plants containing naphthoquinones have been employed for the treatment of different diseases, such as cancer. The biological redox cycle of quinones can be initiated by one electron reduction leading to the formation of semiquinones, unstable intermediates that react rapidly with molecular oxygen generating free radicals. Another alternative is the reduction by two electrons, mediated by DT-diphorase, leading to the formation of hydroquinone. Lapachol, a-lapachone and β-lapachone, isolated from the heartwood of trees of the Bignoniaceae family, are examples of bioactive naphthoquinones. It this review we will discuss the studies involving the activity of lapachol, β-lapachone and derivatives against viruses, Schistosoma mansoni and the pathogenic protozoan Trypanosoma cruzi, Leishmania spp,Toxoplasma gondii and Plasmodium falciparum.

Manuscript ID: molecules-negdis-20081201-za-Egan
Type of Paper: Review
Title: Recent Advances in the Discovery Haem-targeting Drugs for Malaria and Schistosomiasis
Authors: Katherine A de Villiers and Timothy J Egan
Affiliation: Department of Chemistry, University of Cape Town
E-mail: Timothy.Egan@uct.ac.za
Abstract: Haem is believed to be the target of some of the historically most important antimalarial drugs, most notably chloroquine. This target is almost ideal as this haem is host-derived and the process targeted, haemozoin formation, is a physico-chemical process and no equivalent process occurs in the host. The result is that the target remains viable despite resistance to current drugs, which arises from mutations in membrane transport proteins. Recent advances in high throughput screening methods, together with a better understanding of the interaction of existing drugs with this target has created new prospects for discovering novel haem-targeting chemotypes and for target-based structural design of new drugs. Finally, the discovery that Schistosoma mansoni also produces haemozoin suggests that new drugs of this type may be possible not only for malaria, but also for schistosomiasis. These recent developments in the literature are reviewed.

Manuscript ID: Molecules-negdis-20090401-br-Frezard
Title: Pentavalent antimonials: new perspectives for old drugs
Authors: Frédéric Frézard, Cynthia Demicheli, Raul Rio Ribeiro Departamento de Fisiologia e Biofísica-ICB and Departamento de Química-ICEX, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Abstract: Pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate, have been used for more than half a century in the therapy of the parasitic disease leishmaniasis. Even though antimonials are still the firstline drugs, they exhibit several limitations, including severe side effects, the need for daily parenteral administration and drug resistance. The molecular structure of antimonials, their metabolism and mechanism of action are still being investigated. Some recent studies suggest that pentavalent antimony acts as a prodrug that is converted to active and more toxic trivalent antimony. Other works support the direct involvement of pentavalent antimony. Recent data suggest that the biomolecules, thiols and ribonucleosides, may mediate the actions of these drugs. This review will summarize the progress to date on the chemistry and biochemistry of pentavalent antimony. It will also present the most recent works being done to improve antimonial chemotherapy. These works include the development of simple synthetic methods for pentavalent antimonials, liposome-based formulations for targeting the Leishmania parasites responsible for visceral leishmaniasis and cyclodextrin-based formulations to promote the oral delivery of antimony.