Euphorbiaceae orbitides, chemical characterization and synthesis: rational prospection of cyclic peptides with antitumor potential

Author(s)

Jhennifer Priscila Nastri

• Document type: Master's Dissertation
• Press: Araraquara. 2019-05-09.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara
• Defense date: 2019-04-02
• Advisor: Vanderlan da Silva Bolzani

Abstract

Cyclic peptides comprise a class of naturally occurring compoundsin some higher plants and exhibit a wide range of biological activities. These bioactive compounds have aroused the interest from strategic sectors fordrugs and cosmetics development due to their cyclic characteristic, which generates greater affinity and selectivity used todetermine target,due the restriction of rotation of their chemical bonds. The study onorbitides present in Jatropha ribifoliaand Croton sphaerogynus(Euphorbiaceae) wasdivided into the following stages:identification and chemical characterization of compounds, synthesis of orbitidesand antitumor activity.In this study, ribifoline peptidefrom J. ribifoliawas isolated and characterized. In order to evaluate the polarity and the charged at the aminoterminus, the synthesis of three analogous peptides was planned, since substances with higher hydrophobicity have higher antitumor activity according to the literature. Therefore, the serine amino acid has been replaced by alanine (no hydroxyl group), threonine (has an additional methyl group) and lysine (has a positive charge on its side chain). The peptides were synthesized, purified and evaluated in anticancer activity. However, only the cyclic lysine analog generated good growth inhibition for the HCT-116 and MCF-7 cell lines. At the same time, the specie C. sphaerogynus(stem and leaves) was collected in the city Rio de Janeiro-RJ, the vegetal material was extracted in ethanol and fractionated in phase-reversed silica, which allowed toobtain an enriched peptides fraction.From this fraction, it was identify, by the LC-MS technique,possible poly-Leu / Ileorbitides in the leaves and stems of C. sphaerogynus. The spectra MS2allowed to observe mass losses of 113 Da, which allowed to indicate the peptides tetraleucil (or tetraisoleucil), pentaleucil (or pentaisoleucil), hexaleucil (or hexaisoleucil) and heptaleucil (or heptaisoleucil). Preparative HPLC analysis ofthe leaves from this specie also allowed to isolate two flavonoids that were characterized as triglycosylated campperol and rutin.The studies presented showed that C. sphaerogynus has a low diversity of peptides. Added to this, our results showed that unlike the literature, the presence of a positive charge in orbitids is important for its anticancer activity, as observed for ribifoline. (AU)

• FAPESP's process: 17/12326-9 - Orbitides from Croton antisyphiliticus and C. sphaerogynus (Euphorbiaceae), chemical-biological characterization and synthesis: rational prospection of low molecular weight peptides with antitumor potential
• Grantee: Jhennifer Priscila Nastri
• Support Opportunities: Scholarships in Brazil - Master