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Natural metabolites for treating antimicrobial resistant gonorrhoea and visceral leishmaniasis


Neisseria gonorrhoeae (Ng, gonococcus) is the causative agent of the sexually transmitted disease gonorrhoea and affects 78 million people worldwide. Gonococcal infection is frequently asymptomatic but long-term and/or permanent sequelae can develop in individuals. Effective, accessible and affordable antimicrobial treatment is essential for management and control. However, gonococci have evolved resistance to all antimicrobials for gonorrhea treatment and the organism now has earned the epithet of 'Superbug'. Among neglected diseases, leishmaniasis is a protozoan neglected disease that affects approximately 12 million people worldwide. The visceral form (VL) is fatal if untreated and is estimated to cause about 50,000 deaths each year. Chemotherapy remains the most important element in the control of VL, and is highly toxic and shows low efficacy. New treatments are needed. Natural metabolites from plants and microorganisms are a powerful tool for the design of new medicines. The Brazilian flora has been considered a promising source of these small molecules. Among microorganisms, terrestrial and marine bacteria offer an enormous chemo-diversity and have been shown to produce powerful antimicrobial compounds to be used as new scaffolds for Drug Discovery. In this proposal, we aim to explore this link between molecular structure and bioactivity to directly connect biodiversity to the discovery of new medicines. As part of the ongoing FAPESP project 2018/10279-6, Prof. Tempone and Prof. Lago generated a bank of bioactive natural compounds to be used in a lead optimization program for leishmaniasis and Chagas disease. Then, pure and chemically characterized plant metabolites will be tested against resistant strains of Neisseria gonorrhoea at the University of Southampton. In the search for new natural scaffolds for VL, microbial metabolites isolated from different sources, including marine bacteria from Southampton (UK) sea sediments and from pathogenic species of Neisseria sp., will be investigated for the potential antiparasitic activity. Selected bioactive extracts will be subjected to dereplication procedures using LC/MS and NMR to identify the microbial metabolites. By using bio-guided fractionation, active compounds will be isolated and chemically characterized by spectrometric and spectroscopic analysis. We propose to use this pump-priming application as a springboard for studying long-term objectives through the generation of pilot data and collaboration between our groups and institutions. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEMPONE, ANDRE GUSTAVO; DOS SANTOS THEODORO, REINALDO; ROMANELLI, MAIARA MARIA; FERREIRA, DAYANA AGNES SANTOS; AMARAL, MAIARA; DE ASSIS, LETICIA RIBEIRO; CRUZ, LUCAS MONTEIRO SANTA; COSTA, ALAN ROBERTO; ZANELLA, ROSEMEIRE COBO; CHRISTODOULIDES, MYRON; et al. A new reduced chalcone-derivative affects the membrane permeability and electric potential of multidrug-resistant Enterococcus faecalis. Chemico-Biological Interactions, v. 365, p. 8-pg., . (14/18330-0, 21/04464-8, 18/26655-7, 19/11979-4, 17/50333-7, 18/15083-2, 09/53989-4)
AMARAL, MAIARA; VARELA, MARINA T.; KANT, RAVI; CHRISTODOULIDES, MYRON; FERNANDES, JOAO PAULO S.; TEMPONE, ANDRE G.. Synthetic Analogues of Gibbilimbol B Induce Bioenergetic Damage and Calcium Imbalance in Trypanosoma cruzi. LIFE-BASEL, v. 13, n. 3, p. 17-pg., . (21/04464-8, 18/26655-7, 17/50333-7, 18/03918-2, 19/24028-8, 18/25128-3)

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