Cytotoxic cordiaquinones from the roots of Cordia polycephala

Abstract

A investigação química das raízes de Cordia polycephala resultou no isolamento de duas novas naftoquinonas terpenoídicas, 6-[10-(12,12-dimetil-13α-(22-metil-21-butenoilóxi -[10-(12,12-dimetil-13α-(tigloilóxi)-16-metenilciclohexil)etil]-naftaleno-1,4-diona, designadas de cordiaquinonas N (1) e O (2), respectivamente. As cordiaquinonas já conhecidas, B (3), L (4) e E (5), foram também isoladas. Suas estruturas foram elucidadas após detalhada análise dos dados de RMN 1 H e 13 C (1D e 2D) e EMAR (espectrometria de massas de alta resolução). Todas as cordiaquinonas (1-5) foram avaliadas contra quatro linhagens de células cancerígenas: HCT-8 (colo), HL-60 (leucemia), MDA-MB-435 (melanoma) e SF295 (glioblastoma), mostrando IC 50 na faixa de 1,2 a 11,1 mmol L -1 . As novas cordiaquinonas 1 e 2 foram as mais ativas contra todas as linhagens de câncer, enquanto 3 foi mais seletiva para células leucêmicas (IC 50 2,2 μmol L -1 ).The chemical investigation of roots of Cordia polycephala resulted in the isolation of two new terpenoid naphtoquinones, 6-[10-(12,12-dimethyl-13α-(22-methyl-21-butenoyloxy)-16-methenylcyclohexyl)ethyl]-naphtalene-1,4-dione and (6-[10-(12,12-dimethyl-13α-(tigloyloxy)-16-methenylcyclohexyl)ethyl]-naphtalene-1,4-dione, named as cordiaquinone N (1) and O (2), respectively. The known cordiaquinones B (3), L (4) and E (5) were also isolated. Their structures were elucidated after detailed 1D and 2D NMR and high resolution electrospray ionization mass spectrometry (HRESIMS) data analysis. All cordiaquinones (1-5) were evaluated against four human cancer cell lines: HCT-8 (colon), HL-60 (leukemia), MDA-MB-435 (melanoma) and SF295 (glioblastoma), showing IC 50 values in the range of 1.2 to 11.1 mmol L -1 . The new cordiaquinones 1 and 2 were the most active against all cancer cell lines, while compound 3 was selective to leukemia HL-60 cells (IC 50 2.2 mmol L -1 ).

Traditional uses, phytochemistry and pharmacology of the medicinal species of the genus Cordia (Boraginaceae)

“…[64][65][66][67][68][69] Cordiaquinones A, B, E, F, G, H, J and K were studied for antifungal and larvicidal activity. [61,67,70] Cordiaquinone J was found to be active against HL-60 and SF-295 cells with 2.7 lm and 6.6 lm IC 50 value, respectively, when screened for cytotoxicity study.…”

“…Cordiaquinone A (17) C. corymbosa [64] C. curassavica [66] Root Cordiaquinone B (18) C. corymbosa [64] C. curassavica [66] C. linnaei [67] C. polycephala [68] Root Cordiaquinone C (19) C. corymbosa [64] C. linnaei [65] Root Cordiaquinone D (20) C. corymbosa [116] Root Cordiaquinone E (21) C. linnaei [67] C. polycephala [68] Root Cordiaquinone F (22) C. linnaei [67] Root Cordiaquinone G (23) C. linnaei [67] Root Cordiaquinone H (24) C. linnaei [67] Root Cordiaquinone J (25) C. curassavica [66] Root Cordiaquinone K (26) C. curassavica [66] Root Cordiaquinone L (27) C. leucocephala [69] C. polycephala [68] Root Cordiaquinone M (28) C. leucocephala [69] Root Cordiaquinone N (29)…”

“…polycephala [68] Root Cordiaquinone O (30) C. polycephala [68] Root Meroterpenoid benzoquinones (1aS*,1bS*,7aS*,8aS*)-4,5-Dimethoxy-1a,7a-dimethyl-1,1a, 1b,2,7,7a,8,8a-octahydrocyclopropa [3,4]cyclopenta [1,2-b] naphthalene-3,6-dione (31)…”

“…Larvicidal Active against third-instar larvae of Aedes aegypti [220] Methylorsellinate Antiglycation Inhibited the enzyme urease and also showed antiglycation activity [154] Cordiaquinones N and O Cytotoxic Cytotoxic against human cancer cell lines, that is HL-60 (leukaemia), HCT-8 (colon), SF295 (glioblastoma) and MDA-MB-435 (melanoma) [68] Sebestenoids A to D BACE1 inhibitor Moderately inhibit the enzyme aspartic protease BACE1 [115] a-Amyrin Anti-inflammatory Anti-inflammatory activity against experimental model of inflammation in rats [80] Taxifolin 3,5-dirhamnoside Anti-inflammatory Anti-inflammatory activity against experimental model of inflammation in rats [80] Artemetin Anti-inflammatory Reduced carrageenan-induced oedema and cotton pellet granuloma in rats [95] a-Humulene and (-)-transcaryophyllene…”

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

“…Nevertheless, mitomycin C, in combination with other chemotherapeutic drugs, can show acceptable anticancer activities (Alkis et al, 2011;Kornek et al, 2004). Quinones have demonstrated a wide spectrum of activity via numerous mechanisms of action, specifically reactive oxygen species generation, DNA damage, uncoupling of oxidative phosphorylation protein, and inhibition of electron transporters (da Silva et al, 2011;Freitas et al, 2012;Wellington et al, 2019). Among them, versatile studies have shown the generation of semiquinone free radical after one-electron reduction of the quinones and active oxygen species during oxidation-reduction reactions involved in the mechanism of action (Bachur, Gordon, & Gee, 1977;Bayrak et al, 2019;Begleiter, 1985;Glazer, Hartman, & Richardson, 1982;Lown, Begleiter, Johnson, & Morgan, 1976;Lown, Sim, & Chen, 1978;Myers et al, 1977).…”