Chemical composition and antiproliferative, antioxidant and trypanocidal activities of the fruits from Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae)

Abstract Chemical investigation of the extracts of the fruits from Campomanesia xanthocarpa resulted in the isolation of six known compounds identified by NMR and comparison with literature data (2′,4′-dihydroxy-5′-methyl-6′-methoxychalcone (1), 2′,4′-dihydroxy-3′,5′-dimethyl-6′-methoxychalcone (2), 2′-hydroxy-3′-methyl-4′,6′-dimethoxychalcone (3), 2′,6′-dihydroxy-3′-methyl-4′-methoxychalcone (4), 5-hydroxy-7-methoxy-8-methylflavanone (5) and 7-hydroxy-5-methoxy-6-methylflavanone (6)). The considerable antioxidant capacity of the extracts was demonstrated by ORAC-FL and DPPH tests. The antiproliferative assay of the extracts and 5 was done in vitro, against many different cancer cell lines besides a healthy one. The extracts presented low cytotoxicity and the substance demonstrated promising results against all the cancer cell lines tested, with IC50 values ranging from 4.75 to 45.81 µmol L−1. The in vitro trypanocidal activity was evaluated against the epimastigote form of the Y strain of Trypanosoma cruzi and an improvement in the activity of the substances 2 (221.81 µmol L−1) and 5 (61.87 µmol L−1) was observed regarding the values obtained for the extracts. Graphical Abstract


Results and discussion
The extracts (EEF and EEPF) presented similar values for the antioxidant assays (IC 50 of 87.53 ± 1.51 lg mL À1 for EEF and 97.85 ± 1.72 lg mL À1 for EEPF). Different studies have measured the antioxidant activity of extracts of C. xanthocarpa employing the DPPH reagent (Pereira et al. 2012). They show no significant difference to our results. The essential oil from the leaves of C. guazumifolia presented a IC 50 value of 26.1 ± 0.5 lg mL À1 (dos Santos et al. 2017). According to Reynertson et al. (2005), a IC 50 value lower than 50 lg mL À1 is considered very active, 50-100 lg mL À1 moderately active, 100-200 lg mL À1 slightly active and above 200 lg mL À1 is inactive. At the ORAC-FL assay, both extracts showed a distinguished activity, 1013 ± 52 mmol of TE g À1 for EEF and 1099 ± 38 mmol of TE g À1 for EEPF. Comparing these values with the study with the leaves of C. adamantium (Pascoal et al. 2011), EEF and EEPF have a smaller potency. Therefore, comparing with the fruits of Syzygium cordatum, also a specie from the family Myrtaceae, EEF and EEPF have a much higher potency as antioxidant by the ORAC-FL assay (Kucich and Wicht 2016).
Compounds 1, 2, 5 and the extracts (EEF, EEPF) were evaluated for in vitro trypanocidal activity, because they were isolated in higher amounts. The extracts presented similar results, EEF had a IC 50 of 145.11 ± 0.13 mg mL À1 and EEPF had a IC 50 of 149.21 ± 0.14 mg mL À1 . Compound 2 had a IC 50 of 221.81 ± 0.12 mmol L À1 and 5 of 61.87 ± 0.05 mmol L À1 , so 5 showed a better inhibition performance compared to 2. Compound 1 was not effective in this assay (IC 50 > 352 ± 0.1 mmol L À1 ). Benznidazole was employed as positive control and presented a IC 50 of 9.7 mg mL À1 .
The antiproliferative assay was done with the extracts and 5, against eight cancer cell lines and a normal cell line (Table S1). For all the tested cell lines, the extracts (EEF and EEPF) did not show any inhibition effect with TGI values higher than 250 mg mL À1 . However, 5 showed effectiveness for all the cancer cell lines tested with TGI values ranging from 4.75 ± 0.02 to 45.81 ± 0.05 mmol L À1 . For the normal cell line tested (VERO), the TGI value was 51.87 ± 0.06 mmol L À1 . Substance 5 was more effective against the NCI-ADR/RES (resistant ovary) cell line with a TGI value of 4.75 ± 0. 02 mmol L À1 .

Conclusions
EEF and EEPF presented promising results at the antioxidant assays. Six compounds were isolated from the fruits of C. xanthocarpa, 2 and 5 inhibited in vitro trypanocidal activity and also, 5 showed effectiveness for all cancer cell lines tested.

Disclosure statement
No potential conflict of interest was reported by the authors.