Descoberta de fármacos a partir de produtos naturais e a abordagem Molecular Power House (MPH)

Abstract

A descoberta de fármacos a partir de produtos naturais vivencia uma nova era graças ao uso de tecnologias de ponta e abordagens integradas para superar as dificuldades inerentes à pesquisa com produtos naturais. Estes são substâncias químicas altamente complexas e inovadoras produzidas pela biota, em especial organismos sésseis como plantas e micro-organismos, e representam a principal fonte de inspiração de novos fármacos. Resultante do reavivado interesse na descoberta de medicamentos à base de produtos naturais, novas abordagens para a identificação, caracterização, e reabastecimento de produtos naturais estão sendo desenvolvidas, que podem endereçar alguns dos desafios relacionados ao desenvolvimento de fármacos inspirados em moléculas da biodiversidade. Almeja-se a capacidade de detecção e caracterização de novos produtos naturais bioativos, concomitantemente à redução dos custos e tempo para obtenção destas moléculas. Para isto, é necessário inovar nos processos e nas tecnologias aplicadas à descoberta de fármacos a partir de produtos naturais. A abordagem Molecular Power House (MPH) apresentada neste trabalho faz uso de tecnologias integradas como uma forma de superar gargalos clássicos da pesquisa com produtos naturais de plantas, alinhada ao acesso à maior biodiversidade do planeta, posicionando o Brasil no cenário mundial de descoberta de fármacos inovadores.

Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products

“…It is the gap between the fundamental research and the regulatory-demanded non-clinical and clinical tests that finalize the innovation process. This gap still endures, despite the availability of non-refundable funding specifically directed to innovation, perhaps due to the unawareness of its importance and complexity [ 155 ].…”

Searching for new antifungals for the treatment of cryptococcosis

“…Once the antifungal potential is identified, the bioproducts are subjected to extraction, isolation, and identification steps, which include different techniques capable of detecting the presence of compounds and then characterizing them 76 . In summary, the discovery of natural products with antifungal activity generally comprises: 1) classic or virtual cell screening; 2) extraction, isolation of compounds and structural characterization by thin layer chromatography, variations of chromatography associated with mass spectrometry, analysis of carbon 13 nuclear magnetic resonance, and hydrogen nuclear magnetic resonance analysis; 3) pharmacological studies to determine the mode of action; 4) toxicological studies to delineate the substance’s safety; 5) preclinical trials and, if successful; 6) clinical and marketing studies ( Figure 2 ).…”

“…Several new natural products from fungi, bacteria, insects, sponges, algae, and plants have proven to be effective alternatives with the potential to form new drugs that can be effectively used against strains of C. neoformans and gattii 76 - 77 . In recent years, marine sponges and algae have emerged as important sources of new natural products with antifungal activity 78 ; however, plants and fungi are still the most productive sources of antifungal compounds with anticryptococcal activity , including phenols, flavonoids, terpenoids, alkaloids, and peptides, as the main chemical classes represented in these plants 77 .…”

“…However, it is generally accepted that the drug discovery and development processes are time- and resource-intensive. Thus, in recent years, both computational and experimental techniques have played important roles and represent complementary approaches 76 . For a complete review of computer-aided drug design and virtual screening for lead molecules in the discovery of new drugs against Cryptococcus spp., the comprehensive work by Manjunath and Skariyachan (2018) should be consulted 79 .…”