Modificações químicas e biotransformação de diterpenos caurânicos como estratégia para obtenção de derivados com propriedades farmacológicas

Abstract

Kaurane diterpenes, as kaurenoic and grandiflorenic acids, are a class of natural products known to possess a wide spectrum of biological activities such as plant growth regulators, antimicrobial, antiparasite, cytotoxicity, anti-inflammatory activity, fertility inhibitor, among others. Sphagneticola trilobata is a plant commomly found in many regions of Brazil and known to contain high quantities of kaurenoic and grandiflorenic acids. This work aims to isolate these acids from aerial parts of S. trilobata and to make structural modifications through chemical reactions and biotransformations to obtain derivatives, in order to evaluate the effects of such changes in the biological activities in relation to the precursors. Through kaurenoic and grandiflorenic acids, isolated from plant material, were obtained seven derivatives via chemical reactions: ent-kaur-16-oxo-17-nor-9(11)-en-19-oic acid, ent-kauran-16-oxo-17-nor-19-oic acid, ent-13-hydroxy-17-nor-13,16-seco-kauran-19-oic-1613-lactone acid, ethyl ent-kaur-16-en-19-oate, ethyl ent-kauran-16-oxo-17-nor-19-oate and novel compounds ethyl ent-kauran-16-E-oxime-17-nor-19-oate and ethyl ent-kauran-13-lactam-13a-aza-19-oate. The ent-13-hydroxy-17-nor-13,16-seco-kauran-19-oic-1613-lactone acid was subjected to biotransformation reactions using the fungus Penicillium mineoluteum and Fusarium proliferatum. Biotransformation products of F. proliferatum were not isolated, however, from P. mineoluteum, it was isolated the ent-5,15-epoxy-9,10-friedo-10,11-dihydroxy-16,11:19,10-diseco-17-norkauran-16,19-dioic acid 1611:1910-di-lactone, a possible biotransformation product, with 1.31 % yield. Kaurenoic and grandiflorenic acids and their derivatives were tested in relation to antimicrobial and inhibition of acetylcholinesterase enzyme activities. The novel diterpene lactam ent-kauran-13-lactam-13a-aza-19-oate ethyl stood out as inhibitory substance of the yeast Candida albicans, the bacterium Bacillus cereus and of acetylcholinesterase, inducing superior activities relative to kaurenoic acid, its precursor.