ORCID Profile
0000-0001-8606-8644
Current Organisation
Universidade Federal de Lavras
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Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.BIOCHI.2015.11.031
Abstract: Metalloproteases play a fundamental role in snake venom envenomation inducing hemorrhagic, fibrigen(ogen)olytic and myotoxic effects in their victims. Several snake venoms, such as those from the Bothrops genus, present important local effects which are not efficiently neutralized by conventional serum therapy. Consequently, these accidents may result in permanent sequelae and disability, creating economic and social problems, especially in developing countries, leading the attention of the World Health Organization that considered ophidic envenomations a neglected tropical disease. Aiming to produce an efficient inhibitor against bothropic venoms, we synthesized different molecules classified as quinolinones - a group of low-toxic chemical compounds widely used as antibacterial and antimycobacterial drugs - and tested their inhibitory properties against hemorrhage caused by bothropic venoms. The results from this initial screening indicated the molecule 2-hydroxymethyl-6-methoxy-1,4-dihydro-4-quinolinone (Q8) was the most effective antihemorrhagic compound among all of the assayed synthetic quinolinones. Other in vitro and in vivo experiments showed this novel compound was able to inhibit significantly the hemorrhagic and/or proteolytic activities of bothropic crude venoms and isolated snake venom metalloproteases (SVMPs) even at lower concentrations. Docking and molecular dynamic simulations were also performed to get insights into the structural basis of Q8 inhibitory mechanism against proteolytic and hemorrhagic SVMPs. These structural studies demonstrated that Q8 may form a stable complex with SVMPs, impairing the access of substrates to the active sites of these toxins. Therefore, both experimental and structural data indicate that Q8 compound is an interesting candidate for antiophidic therapy, particularly for the treatment of the hemorrhagic and necrotic effects induced by bothropic venoms.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2017
DOI: 10.1038/S41598-017-04643-3
Abstract: Enabling control over macromolecular ordering and the spatial distribution of structures formed via the mechanisms of molecular self-assembly is a challenge that could yield a range of new functional materials. In particular, using the self-assembly of minimalist peptides, to drive the incorporation of large complex molecules will allow a functionalization strategy for the next generation of biomaterial engineering. Here, for the first time, we show that co-assembly with increasing concentrations of a highly charged polysaccharide, fucoidan, the microscale ordering of Fmoc-FRGDF peptide fibrils and subsequent mechanical properties of the resultant hydrogel can be easily and effectively manipulated without disruption to the nanofibrillar structure of the assembly.
Publisher: Wiley
Date: 25-09-2013
DOI: 10.1002/POLB.23386
Publisher: Oxford University Press (OUP)
Date: 08-2019
DOI: 10.1111/LAM.13171
Abstract: Natural enzyme inhibitors have been widely described in literature because of its pharmacological and cosmetic applications. Fungi found in caves represent a promising source of bioactive substances that are still little explored scientifically. Thus, the present work evaluated the presence of enzymatic modulators in a filtrate obtained from the cultivation of the cave fungus Lecanicillium aphanocladii (Family: Cordycipitaceae). Snake venoms from Bothrops alternatus and Bothrops atrox were used as an enzymatic source for the induction of the phospholipase, proteolytic, thrombolytic, cytotoxic and coagulant activities. Compounds present in the fungal filtrate inhibited 50, 23·8, 26·6, 50·9 and 52·5% of the proteolytic, phospholipase, haemolytic, thrombolytic and coagulant activities respectively. The filtrate was not cytotoxic on erythrocytes, but induced partial dissolution of thrombi. Fungal enzyme inhibitors that have low or no toxicity and can be obtained on a large scale and at low cost are relevant in the medical-scientific context. Therefore, the inhibition of phospholipases A2 and proteases observed in the present work highlights the potential of fungal metabolites for the development of drugs that can be used in the treatment of haemostasis and inflammation-related disorders. In this study, secondary metabolites synthesized by Lecanicillium aphanocladii, a fungus isolated from caves, demonstrated modulating action on proteases and phospholipases A2 present in snake venoms of the Bothrops genus, widely used as tools for the study of pathophysiology processes related to haemostasis and inflammation. The results suggest the possibility of future applications for these metabolites in the development of pharmaceuticals of medical-scientific interest.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0FD90017F
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.NANO.2016.01.009
Abstract: The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Elsevier BV
Date: 10-2004
No related grants have been discovered for Andrew Parnell.