Gabriel Franco dos Santos

The Remarkable Structural Diversity Achieved in ent-Kaurane Diterpenes by Fungal Biotransformations

The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant species and a myriad of biological activities has been related to these compounds. Studies on structure versus activity have showed that, in most cases, in kaurane diterpenes, activity increases with the increase of functionalization. Since naturally occurring kaurane diterpenes usually have limited functional groups to be used as targets for semi-synthetic modifications, production of more polar derivatives from kaurane diterpenes have been achieved mostly through the use of fungal biotransformations. In this review, selected examples the wonderful chemical diversity produced by fungi in kaurane diterpenes is presented. This diversity includes mainly hydroxylation of nearly all carbon atoms of the kaurane molecule, many of them carried out stereoselectively, as well as ring rearrangements, among other chemical modifications. Sources of starting materials, general biotransformation protocols employed, fungi with most consistent regioselectivity towards kaurane skeleton, as well as biological activities associated with starting materials and products are also described.

New AChE inhibitors from microbial transformation of trachyloban-19-oic acid by Syncephalastrum racemosum

Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2-3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1-4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimers disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50 = 0.06 μM, which is about six times higher than activity found for galanthamine (IC50 = 0.38 μM), the positive control used in this assay.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-β-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

Structure-activity relationship study of diterpenes for treatment of Alzheimer’s disease

Gabriel F. dos Santosa, Rondinelle G. Pereiraa, Maria A. D. Boaventuraa, Francisco A. Maciasb, Gesiane da S. Limaa, Amanda C. S. Coelhoa, Jose M. G. Molinillob, Antonio Calab, and Jacqueline A. Takahashia,* Department of Chemistry, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 31270-901 Belo Horizonte – MG, Brasil Department of Organic Chemistry, Institute of Biomolecules, Campus CEIA3, School of Science, University of Cadiz, C/ Republica Saharaui, 7, 11510-Puerto Real (Cádiz), Spain

Fungos Filamentosos e Química: Velhos Conhecidos, Novos Aliados

Fungos sao classicamente associados com problemas como a deterioracao e contaminacao de alimentos, micoses humanas e doencas que trazem prejuizos a agricultura. Entretanto, o potencial biotecnologico destes organismos supera enormemente os potenciais danos e o numero de especies fungicas com importância quimica, farmacologica, ambiental, ecologica, agricola e alimenticia e extraordinario. Neste campo, a quimica ajudou a entender os processos fermentativos e o metabolismo fungico, potencializando as aplicacoes de processos e metabolitos fungicos. A quimica tambem tem ajudado a controlar a presenca de fungos quando a mesma e indesejada, fornecendo agentes conservantes para alimentos e cosmeticos, antioxidantes, antimicoticos e antifungicos para uso agricola. No entanto, a interdisciplinaridade do estudo do metabolismo fungico tem trazido novos e interessantes desafios. Nesta revisao serao abordados aspectos importantes sobre o cultivo, identificacao, utilizacao e potencial biotecnologico de fungos e seus metabolitos partindo da perspectiva do seu uso historico. Em seguida, serao apresentados aspectos atuais da utilizacao de fungos para beneficio da vida humana, como o desenvolvimento de novos farmacos, aplicacoes ambientais e ecologicas como o uso de biorremediacao, alem de se apresentar novas fronteiras para a pesquisa, como a busca de fungos em novos habitats, o uso de condicoes de cultivo desafiadoras para elicitacao da producao metabolica e o uso de tecnicas analiticas modernas para ampliar a aplicacao biotecnologica de fungos.