ANTIANGIOGENIC ACTIVITY OF THE ALKALOID SKIMMIANINE ISOLATED FROM ZANTHOXYLUM COCO.

CANDELA R. NIN; GASTÓN SORIA; MARÍA C. CARPINELLA; MARIANA B. JORAY

Congreso; Reunión Conjunta SAIC SAI AAFE NANOMED.AR; 2021

The term angiogenesis refers to the development of new blood vessels from the preexisting vasculature. Under physiological conditions, this process is strictly regulated being focal and self-limited in time. Nevertheless, disbalances between the biochemical signals that regulate angiogenesis may occur, resulting in a chronic neovascularization that takes part in a large number of diseases including neoplastic transformation, rheumatoid arthritis, psoriasis, and different ocular conditions. In this context, the development of new agents capable of downregulating pathological angiogenesis become relevant in the field of drug discovery. The flora from Argentina stands out among the different sources of new bioactive molecules. In previous studies conducted by our research team, the ethanol extract of Zanthoxylum coco showed a remarkable antiangiogenic effect. Therefore, this species was submitted to the bioassay guided isolation of its active principle. This process involved the alternation of different chromatographic techniques with the evaluation of the antiangiogenic activity in terms of the tube formation assay. One compound identified by diverse spectroscopic techniques as the alkaloid skimmianine was isolated. This molecule significantly inhibited tube formation even at 12.5 ug/mL. HPLC analysis showed that this compound is one of the major constituents of the ethanol extract of Z. coco. No toxic effect against peripheral blood mononuclear cells, used as model of normal cells, was observed. Additionally, the compound did not affect the integrity of the erythrocyte membrane. Pharmacokinetic and drug-likeness parameters were evaluated by SwissADMET online tool. The obtained results support the potential of the flora from Argentina as a source of new small molecules capable of downregulating neovascularization and position this naturally occurring alkaloid as a promising lead for the development of new analogs with improved antiangiogenic activity.