Copaifera multijuga, Copaifera pubiflora and Copaifera trapezifolia Oleoresins: Chemical Characterization and in vitro Cytotoxic Potential against Tumoral Cell Lines

Abstract

Copaifera species (Fabaceae) comprises approximately 70 species of large trees, from which 16 can be found in Brazil. The oleoresins obtained from their trunk are widely used in Brazilian folk medicine, which display important antitumoral potential. Chemically, these oleoresins are mainly composed of a mixture of sesquiterpenes and diterpenes. In this paper we are describing the isolation and identification of 12 already known terpenes from oleoresins obtained from three different Copaifera species (C. multijuga, C. pubiflora and C. trapezifolia) and 2 novel diterpenes (ent-16-hidroxy-3,13 clerodadien-15,18-dioic acid and ent-labda-5,13-dien-15-oic acid) from C. trapezifolia. Both new compounds were identified by nuclear magnetic resonance (NMR) spectroscopic (1 H and 13 C NMR, correlation 1 H-1 H (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)) and by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) analyses. The cytotoxic potential of these oleoresins, their main non-volatile compounds and their volatile compound fractions were evaluated against a panel of tumoral (MCF-7, ACP01, A549, HeLa) and normal cell lines (MCF-10A, GM07492-A) through XTT (tetrazolium salt) and SRB (sulforhodamine B) assays. The novel diterpene ent-labda-5,13-dien-15-oic acid displayed relevant cytotoxic effect against most of the cancer cell lines with mean inhibitory concentration (IC 50) values ranging from 3.57 ± 1.12 to 22.56 ± 1.03 µg mL-1 , and a high selectivity level in both assays.

Oleoresins and naturally occurring compounds of Copaifera genus as antibacterial and antivirulence agents against periodontal pathogens

“…1 ) polyalthic acid ( 1 ), kaurenoic acid ( 2 ), hardwickiic acid ( 3 ), ent -copalic acid ( 4 ) and its isomer [(13E)- ent -labda-7,13-dien-15-oic acid] ( 5 ), ent -agathic acid ( 6 ), ent -agathic acid 15-methyl ester ( 7 ), ent -agatholic acid 15-methyl ester ( 8 ), ent -agatholic acid ( 9 ), and junenol ( 10 ) were isolated from the oleoresins obtained from Copaifera spp. and identified by our research group as described previously 22 , 23 , 30 , 32 – 34 .

Figure 1 Chemical structures of the tested compounds: polyalthic acid ( 1 ), kaurenoic acid ( 2 ), hardwickiic acid ( 3 ), ent -Copalic acid ( 4 ) and its isomer [(13E)- ent -labda-7,13-dien-15-oic acid; 5 ], ent -agathic acid ( 6 ), ent -agathic acid 15-methyl ester ( 7 ), ent -agatholic acid 15-methyl ester ( 8 ), ent -agatholic acid ( 9 ), and junenol ( 10 ).

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Isolation of diterpenes from Araucaria sp Brazilian brown propolis and development of a validated high‐performance liquid chromatography method for its analysis

“…The brown propolis produced in Paraná state ( BPSP ) has Araucaria sp, a typical tree from south of Brazil, as the primary botanical source. Araucaria tree exudates a resin composed predominantly of a mixture of acid diterpenes, a secondary class of plant metabolites displaying several biological activities, highlighting antimicrobial [10], vasorelaxant [11], antiparasitic [12], and cytotoxic against cancer cell lines [13]. In addition, some diterpenes isolated from BPSP are highly effective in inhibiting several human cancer cell line growths, suggesting that BPSP would have anticancer properties [14].…”

Avaliação das atividades citotóxica, anti-inflamatória e antinociceptiva da oleorresina de >i<Copaifera pubiflora>/i< Benth e de seu metabólito majoritário ácido >i<ent-hardwíckiico>/i<

“…A oleorresina se apresenta como um liquido com cor e viscosidade variáveis, variando do amarelo ao marrom claro, composta por uma fase sólida ou resina com uma poção não volátil composta principalmente por diterpenos ácidos, e uma parte oleosa volátil, constituída por uma mistura de sesquiterpenos. As oleorresinas são amplamente utilizadas na medicina popular e a maioria dos estudos publicados são relacionados à sua composição química e atividades farmacológicas (ARRUDA et al, 2019;CARNEIRO et al, 2020). A variação na composição química das oleorresinas é influenciada por muitos fatores, tais como diferenças metabólicas entre indivíduos da mesma espécie ou de espécies distintas, espécies botânicas, sazonalidade e tipo de plantio.…”

“…Nos últimos anos, os estudos de várias espécies levaram ao isolamento de um grande número de terpenos que possuem variadas propriedades farmacológicas, como atividades anti-inflamatória, antibacteriana, leishmanicida, dentre outras (ARRUDA et al, 2019;CARNEIRO et al, 2020;PIERI et al, 2012b;PRISINZANO;ROTHMAN, 2008;RIBEIRO et al, 2018).…”

“…O ácido ent-hardwíckiico (ácido ent-15,16-epóxi-3,13(16),14-clerodatrieno-18óico), (Figura 3), é um diterpeno do tipo clerodano muito abundante nas oleorresinas de copaíbas (LEANDRO et al, 2012). Alguns estudos realizados com este metabólito demonstraram uma significativa atividade antibacteriana, antifúngica e leishmanicida (CARNEIRO et al, 2020;CRENTSIL et al, 2020;DE S. VARGAS et al, 2015). Além disso, o potencial antinociceptivo e anti-inflamatório do ácido ent-hardwíckiico foi recentemente descrito (CAI et al, 2019;DE S. VARGAS et al, 2015).…”