Obtaining structural analogues of pimaradienoic acid through the process of fungal biotransformation and study of the effect of these metabolites on the activity of the TcDHODH enzyme and on the contraction of the vascular smooth muscle of the aorta artery of mice

Abstract

The present work has the general objective of obtaining structural analogues of pimaradienoic acid, a diterpene present in large quantity in the roots of Viguiera arenaria Baker, which has proven a significant capacity to inhibit the contractile response of the vascular smooth muscle of mice, due to its capacity to reduce the influx of Ca+2 through the blocking of the channels operated by voltage and receiver. In addition to this well-established activity, preliminary studies showed the arterial pressure of mice normotense in vivo, as well as inhibiting the dihydroorotate dehydrogenase enzyme of Trypanossoma cruzi (TcDHODH), an excellent pharmacological target for the discovery of new potentially promising substances to combat parasites that cause Chagas disease. The structural modifications proposed in this Project will be achieved through the technique of fungal biotransformation, using four different genuses of fungus, so as to guarantee the variability of the analogues produced. The diterpenes isolated and identified will then be evaluated on the inhibitory capacity of the TcDHODH enzyme and the contraction of the vascular smooth muscle in the aorta of mice, with the aim of selecting new compounds more active than pimaradienoic acid, so that in a stage beyond the development of this Project they can be tested with regard to their antihypertensive and trypanocide potential. (AU)