Since the beginnings of our studies about the natural products, (S)-(+)-Boldine (2,9-dihydroxy-1,10-dimethoxy-N-methyl-4H-dibenzo[de,g]quinoline) from boldo tree (Peumus boldus Molina. Monimiaceae), native to the central region of Chile, it has shown wide pharmacological activities unknown for many people. Thus, it has been characterized in the past few years as an antioxidant that effectively protects different systems against free-radical-induced lipid peroxidation or enzyme inactivation. Taking into account these references, when (S)-(+)-Boldine was brominated, chlorinated and iodinated by using molecular bromine in acetic acid or N-halosuccinimides in trifluoroacetic acid, there they were afforded 3-haloboldines- and 3,8-dihaloboldines. Radioligand binding studies of these products showed that halogenation of boldine at C-3 favors affinity for D1 (vs D2-) dopaminergic receptors, attaining a low nanomolar IC50 value in the case of 3-iodoboldine (http://pubs.acs.org/doi/abs/10.1021/np990433j).
On the other hand, we are interested in studying new compounds with aporphine skeleton that to have wide pharmacological possibilities such as boldine. In this sense, a small group of isoquinoline alkaloids called "Oxoisoaporphine" (7H-dibenzo[de,h]quinolin-7-one) have been few study, whilst these compounds bearing different substitution patterns, can be isolated from Menispermum dauricum DC (Menispermaceae). Due to the interest of these compounds in the scope of the pharmacology of the isoquinoline derivatives such as the oxidated isomers of the aporphine called "Oxoaporphine" (7H-dibenzo[de,g]quinolin-7-one), "in vitro" assays of human monoamine oxidase inhibition (h-MAO) with several oxoisoaporphines, it allowed us to find derivatives with high selectivity for the isoform A (h-MAO-A). This fact will allow us to synthesize drugs of this alkaloid with low cost and with a wide variety of substitution patterns to the treatment of pathologies of major depressive disorder (http://www.wipo.int/pctdb/en/wo.jsp?WO=2009034216).
Recently our research about the oxoisoaporphines pharmacology, in collaboration with the IRD (Institut de Recherche pour le Développement, France), we can to obtain unusual and selective results in the treatment "in vitro" of the Malaria, a tropical disease caused by the plasmodium parasite, Plasmodium falciparum. Our efforts are now directed in the discovery of new drugs against the Leishmaniasis, disease caused by protozoan parasites that belong to the genus Leishmania, and is transmitted by the bite of certain species of sand fly (subfamily Phlebotominae).
According to the our new investigation about the carrier of several drugs through Central Nervous System (CNS), cell of different organs like liver, lung, heart, etc. potentially useful in the treatment of cancer, viral diseases and tropican infections that affect an important population in countries of the third world as the Malaria, we must consider the primary purpose of drug delivery systems such as to deliver the necessary amount of drug to the targeted site for a certain period of time., both efficiently and precisely. The important of carrier systems that can be versatile and from natural source for their low cost, it had contributed to development and study of cyclodextrin (CD) systems composed by sugar units as glucose. Cyclodextrins are potential candidates for such a role, because of their ability to alter physical, chemical, and biological properties of guest molecules through the formation of inclusion complexes.
Our preliminary results with ß-cyclodextrin with its derivatives (HP-ß-CD, DIME-ß-CD) with two different type of compounds from natural source as coumarins and naphtho-quinolinone have been studied, due to the important fact of that both are DNA-well known intercalators framework useful in the treatment of cancer, but a few variety of these compounds are used with CD.