Diterpenos latirânicos de Jatropha mollissima (Pohl.) Baill. e avaliação de atividade citotóxica

Abstract

Jatropha mollissima (Pohl.) Baill., a species belonging to the Euphorbiaceae family, is endemic to the Caatinga biome and is commonly known as "pinhão-bravo," "pinhão de purga," or "pinhão vermelho." This species is characterized as a shrub, and its reddish latex is widely used in traditional medicine for the treatment of ulcers and snakebite envenomation. Despite its ethnopharmacological relevance, phytochemical studies on this species remain scarce. However, the literature has reported cytotoxic, antimicrobial, antioxidant, antiparasitic, and larvicidal activities.The main objective of this study is to contribute to the phytochemical and pharmacological knowledge of J. mollissima through the isolation of secondary metabolites and the evaluation of in vitro cytotoxic activity. Root samples were collected in the municipality of Serra Branca, in the state of Paraíba, Brazil. A voucher specimen was deposited at the Lauro Pires Xavier Herbarium (JPB) of the Federal University of Paraíba (UFPB) under the code JPB 37920 and registered in the National System for the Management of Genetic Heritage and Associated Traditional Knowledge (SisGen) under code AB27FD4.Following collection, the plant material was identified, dried, and pulverized. The root powder was subjected to exhaustive extraction by maceration for seven days, with the process repeated three times. The resulting extractive solution was concentrated to obtain the Hexane Root Extract of J. mollissima (EHJM-R), which was subsequently defatted with acetonitrile to reduce nonpolar interfering substances. The Defatted Hexane Root Extract (dEHJM-R) was fractionated by column chromatography (CC), yielding thirty-seven fractions, which were monitored by analytical thin-layer chromatography (TLC). Of these, two fractions (Fr18 and Fr23) displayed superior chromatographic profiles and were selected for analytical and preparative High- Performance Liquid Chromatography (HPLC) for compound isolation.All isolated compounds were identified and/or characterized by Mass Spectrometry (MS), Nuclear Magnetic Resonance Spectroscopy (NMR), and Infrared Spectroscopy (IR). The dEHJM-R, Fr18, and Fr23 were evaluated for in vitro cytotoxic activity against colorectal cancer (HCT-116) and melanoma (SK-MEL-28) cell lines, as well as against the non-tumoral human keratinocyte cell line (HaCaT), using the MTT assay.The phytochemical investigation led to the isolation of six lathyrane-type diterpenes: jatrogrossidione, 2-epi-hydroxyisojatrogrossidione, 15-epi-4E- jatrogrossidentadione, 15-epi-4Z-jatrogrossidentadione, and multifidione, all reported for the first time in this species, as well as jatromollissimadione, a novel compound not previously described in the literature. Fraction Fr23 exhibited significant in vitro cytotoxic activity against SK-MEL-28 and HCT-116 cell lines, although it also inhibited the non-tumoral HaCaT cell line. The dEHJM-R and Fr18 demonstrated moderate cytotoxic activity across all cell lines tested. Therefore, the present study highlights J. mollissima as a promising bioresource of lathyrane diterpenes and reveals its potential in vitro anticancer activity, thus contributing to and expanding its pharmacochemical potential.