New cytotoxic bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch

Abstract

Three new bufadienolides 14β, 16β-dihydroxy-3β-[β-D-glucopyranosyl-(1→6)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (1), 14β-hydroxy-3β-[β-D-glucopyranosyl-(1→4)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (2) and hellebrigenin-3-O-β-D-glucosyl-(1→4)-β-D-glucoside (3), together with eight known bufadienolides (4–11) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by extensive spectroscopic methods and acid hydrolysis. Compounds 1–7 were evaluated for their cytotoxic activity against HCT116, A549 and HepG2 tumor cell lines. Compound 1 exhibited moderate cytotoxicity against HepG2 cells with IC₅₀ value of 15.1?±?1.72?μM. Compounds 5 and 6 exhibited moderate cytotoxicity against HCT116 cells with IC₅₀ values of 15.12?±?0.58?μM and 13.17?±?2.34?μM, respectively.     

A new rearranged abietane diterpene from Clerodendrum inerme with antioxidant and cytotoxic activities

Eight compounds were isolated from the leaves of Clerodendrum inerme, including one new rearranged abietane diterpene, crolerodendrum B (1). Their structures were determined by means of spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance (1-D and 2-DNMR), high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and circular dichroism (CD). The DPPH radical scavenging and cytotoxic activities of isolated compounds against MCF7 (breast), HCT116 (colon) and B16F10 (melanoma) cancer cell lines were evaluated. Compounds 1, 3 and 4 exhibited strong DPPH radical-scavenging effects (ED₅₀ values of 17.6 ± 2.1, 10.1 ± 0.8 and 11.3 ± 0.3 μM, respectively) and 4 showed strong cytotoxicity against the HCT116 cell line (IC₅₀ = 3.46 ± 0.01 μM).     

New macrocyclic diterpenes from Euphorbia connata Boiss. with cytotoxic activities on human breast cancer cell lines

Acetone:chloroform (1:2) extract of the aerial parts of Euphorbia connata Boiss. (Euphorbiaceae) was investigated for its diterpenoids. This led to the isolation of one known and two new diterpenes, belonging to the pentahydroxy-13(17)-epoxy-8,10(18)-myrsinadiene and tetrahydroxy-5,6-epoxy-14-oxo-jatropha-11(E)-ene classes. The structures were elucidated based on ¹³C and ¹H NMR as well as 2D NMR, IR and MS spectra and the cytotoxicity for compounds 1–3 were evaluated by using MTT assay against two human breast cancer cell lines. Myrsinane-type compounds – 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (1) and 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (2) – exhibited moderate inhibitory effects, with IC₅₀ values of 24.53 ± 3.39 and 26.67 ± 1.41 μM against the MDA-MB cell line, and 37.73 ± 3.41 and 34.57 ± 2.12 μM against the MCF-7 cell line, respectively. Jatrophane-type diterpene – 5,6-epoxy-8,9,15-triacetyl-3-benzoyl-14-oxo-jatropha-11(E)-ene (3) – showed weak cytotoxicity, with IC₅₀ values of 55.67 ± 7.09 μM against MDA-MB, and moderate cytotoxicity with IC₅₀ values of 24.33 ± 3.21 μM against MCF-7 cell line.     

Cytotoxic triterpene saponins from the mangrove Aegiceras corniculatum

Using various chromatographic separations, sixteen compounds, including one new triterpene saponin named aegicoroside A (1), were isolated from the leaves of the Vietnamese mangrove Aegiceras corniculatum. Their structures were determined by spectroscopic methods such as 1D and 2D NMR and HR-ESI-MS. The cytotoxic activities of the isolated compounds against MCF7 (breast), HCT116 (colon), B16F10 (melanoma), and A549 (adenocarcinoma) cancer cell lines were also evaluated. Strong cytotoxicity was observed for sakurasosaponin (2) against all four cancer cell lines and for sakurasosaponin methyl ester (3) against MCF7, A549, and HCT116 cell lines with IC₅₀ values ranging from 2.89 ± 0.02 to 9.86 ± 0.21 μM.     

Three new biflavonoids from the branches and leaves of Cephalotaxus oliveri and their antioxidant activity

Three new biflavonoids, named oliveriflavones A-C (1–3), together with two known flavonoids (quercetin (4) and rutin (5)), were isolated from the endangered plant Cephalotaxus oliveri. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, UV, and CD spectra. Compounds 1–5 were first isolated from the genus Cephalotaxus. All the compounds were tested for their antioxidant activity. Compounds 4 and 5 showed excellent activity with IC₅₀ values of 0.03 ± 0.06 μM and 0.02 ± 0.10 μM, respectively.     

Calaxanthones A-C,three new xanthones from the roots of Calophyllum calaba and the cytotoxicity

Three new xanthones, named calaxanthones A-C (1–3), along with 17 known xanthones (4–20) were isolated from the roots of Calophyllum calaba. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell lines with IC₅₀ values in the range of 0.82–5.04 μM. Furthermore, compound 6 showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC₅₀ values of 7.06, 5.27 and 9.64 μM, respectively. Additionally, compound 7 showed potent cytotoxicity against KB cell with an IC₅₀ value of 4.62 μM.     

Polymeric seven-coordinated organotin(IV) complexes derived from 5-amino-2-chlorobenzoic acid and in vitro anti-cancer studies

Cancer cases are alarmingly increasing worldwide, and newer chemotherapeutic agents are needed. Recent analogs of cisplatin (carboplatin, lobaplatin, nedaplatin and oxaliplatin) and their marketing as advanced chemotherapeutic drugs have furthered the interest in metal-based anti-cancer drugs. In the current study, two new polymeric organotin(IV) carboxylate complexes (1 and 2) have been synthesized and characterized. Spectroscopic studies showed that coordination took place via carboxylates. Furthermore, X-ray crystallographic study on 1 indicated that it possesses a monomeric structure and exists in polymeric formation due to additional Sn–N coordination, assigning seven coordinations to each metal ion. Both the complexes were tested against three cancerous (human colon cancer, HCT 116; breast cancer, MCF-7; and leukemia, K562) and one non-cancerous (3T3-L1) cell lines. Complex 1 showed exceptional cytotoxicity against cancerous cell lines (IC₅₀ = 1.0 μM for HCT 116; 258.7 nM for MCF-7; and 46.7 nM K562) and remained comparatively non-toxic against normal cells (IC₅₀ = 37.0?μM). This shows that both complexes have selective cytotoxicity against cancer cells.     

Two new polyhydroxylated triterpenoids from Salvia urmiensis and their cytotoxic activity

Two new polyhydroxylated triterpenoids were isolated from the acetone extract of the aerial parts of Salvia urmiensis Bunge. Their structures were elucidated by 1D and 2D NMR and HR-ESI-MS analyses as olean-12-ene-1β,3β,11α,22α-tetraol (1) and urs-12-ene-1β,3β,11β,22α-tetraol (2). The effect of these compounds on cell viability of MCF-7 cells was investigated by the MTT assay. Compounds 1 and 2 showed weak cytotoxicity with IC₅₀ values of 110.23 ± 0.12 and 88.35 ± 0.09 μM, respectively.     

Cytotoxity of two new coumarin derivatives isolated from Launaea mucronata

The chloroform fraction of methanol (MeOH) extract of the aerial parts of Launaea mucronata was in vitro investigated for cytotoxicity against HCT116, HepG2 and MCF-7 cell lines, and resulted with IC₅₀ = 20.0, 18.6 and 14.30 μg/mL, respectively. The chloroform fraction of the MeOH extract was subjected to further fractionation, which led to the isolation of two new coumarin compounds (6-isobutyl coumarin and 6-isobutyl-7-methyl- coumarin). The structures of the new compounds were elucidated by high field 1D and 2D NMR and ESI-MS spectroscopies. Low polar fractions revealed the isolation of other known triterpene compounds which were identified according to its spectral data and comparison with the literature. New coumarin compounds show high cytotoxicity against MCF-7, HCT116 and HepG2 cell lines.     

Atalantums H-K from the peels of Atalantia monophylla and their cytotoxicity

Abstract

Four new benzoyltyramines, atalantums H-K (1–4) and seven known compounds were isolated from the peels of Atalantia monophylla. All compounds were tested for cytotoxicity against HeLa, HCT116 and MCF-7 cell lines, as well as normal cells (Vero cells). Compound 5 showed cytotoxicity against HeLa, HCT116 and MCF-7 cell lines with IC₅₀ values ranging from 16-25?μg/mL but was inactive against Vero cells. Compound 6 also showed interesting results as compound 5 with IC₅₀ values ranging from 15-18?μg/mL and an IC₅₀ value of 80.20?μg/mL against Vero cells. This means compounds 5 and 6 can be used as lead compounds for anticancer agents.     

Antiproliferative and cytotoxic secondary metabolites from fruits of Leplaea mayombensis

Two new seco-lanostane-type triterpenes, named mayomlactones A (1) and B (2) were isolated from the fruits of Leplaea mayombensis together with 10 known compounds (3–12). Structures of the new compounds were elucidated by extensive spectroscopic studies. Except compounds 11 and 12, all the other chemical compounds are newly reported from Leplaea genus. From the results of this investigation, compounds 1–10 were examined for antiproliferative activity against HeLa cells as well as cytotoxicity against 3T3 cell line. Compounds 3 and 4 showed moderate antiproliferative activity with IC₅₀ values of 10.4 ± 0.1 and 18.6 ± 0.2 μM, respectively. On the other hand, compounds 1, 4 and 9 showed weak cytotoxicity with IC₅₀ values 44.1 ± 0.5, 55.8 ± 0.7 and 55.1 ± 0.5 μM. Overall, none of the tested compounds showed good selectivity (SI ranging from 0.51 to 3.06) but high toxicity against the 3T3 cell line.     

Hepatoprotective and neuroprotective tocopherol analogues isolated from the peels of Citrus unshiu Marcovich

Three tocopherol analogues methoxytocopherol (1), α-tocopherol (2) and γ-tocopherol (3) were isolated from the peels of Citrus unshiu Marcovich. The protective effects of the isolated compounds against tert-butyl hydroperoxide-induced hepatotoxicity in human liver-derived HepG2 cells and glutamate-induced oxidative stress in HT22-immortalised hippocampal cells were evaluated. Compounds 1–3 were significantly protective in HepG2 cells with EC₅₀ values of 21.22 ± 2.01, 25.21 ± 2.11 and 25.25 ± 1.21 μM, respectively, and in HT22 cells, compounds 1–3 had EC₅₀ values of 20.62 ± 1.36, 6.44 ± 1.65 and 9.52 ± 1.54 μM, respectively.     

Two new polyketides from the fungus Penicillium oxalicum MHZ153

Two new polyketides, penicilloxalones A (1) and B (2), together with 13 known compounds (3–15), were isolated from the ethyl acetate extract of the solid substrate fermentation cultures of the fungus Penicillium oxalicum MHZ153. The structures of the isolates were determined by spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 7 and 11 showed inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC₅₀ values of 0.9 ± 0.2 μM and 87.9 ± 0.7 μM, respectively.     

A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica

One new chalcone-flavone biflavonoid, 3′-hydroxydaphnodorin A (1), together with 12 known biflavonoids (2–13), was isolated from the rhizome of Wikstroemia indica. Their structures were established on the basis of extensive spectroscopic methods. Eight isolated compounds 1–3, 6, 7, 9, 12 and 13 were evaluated for their cytotoxic activities against cancer-derived cell lines Hep3B, HepG2 and CNE2, and 1 was found to possess moderate cytotoxicity against HepG2 and CNE2 cell lines, with IC₅₀ values of 65.5 ± 11.4 and 53.6 ± 10.1 μM, respectively.     

A new abietane diterpenoid glycoside from ajuga ovalifolia var. calantha

A new abietane diterpenoid glycoside, ajugaside B (1), along with three known compounds (2–4), were isolated from the whole plants of Ajuga ovalifolia var. calantha. The structure of the new compound (1) was elucidated by means of spectroscopic analyses (HRESIMS, IR, NMR and ECD). All of the isolated compounds were evaluated for their antitumor activities against MGC803, MCF-7, A549, HT29 and HepG2 cell lines. Compounds 3–4 showed moderate cytotoxicity against all tested cell lines with IC₅₀ values of 1.8–7.3?μM.     

Two new benzophenones from endohydric moss Polytrichum Commune

Two new benzophenones (1 and 2), were isolated from the endohydric moss Polytrichum commune. Their structures were elucidated by spectroscopic methods including extensive 2?D NMR techniques. Compound 2 is the first example of benzophenone with a rare cyclopropylacetamide from the natural resources. Compounds 1 and 2 were screened their cytotoxicity against five cancer cell lines (HCT-116, A-549, MCF-7, HepG2, A-375,), and no cytotoxic activities were observed (IC₅₀ > 100?μM).     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

New Labdane diterpenes from Hedychium yunnanense with cytotoxicity and inhibitory effects on nitric oxide production

Two new labdane diterpenes, hedychenoids A (1) and B (2), were isolated from the rhizomes of Hedychium yunnanense, together with four known ones hedychenone (3), forrestin A (4), villosin (5) and calcaratarin C (6). Their structures were determined on the basis of NMR (1D and 2D) and mass spectroscopic analysis. Compounds 2, 3 and 5 exhibited cytotoxicity against SGC-7901 with IC₅₀ values of 14.88 ± 0.52, 7.08 ± 0.21 and 7.76 ± 0.21 μg/ml, 3 and 5 against HeLa with IC₅₀ values of 9.76 ± 0.48 and 13.24 ± 0.63 μg/ml, respectively. Compounds 2, 5 showed inhibitory effects against nitric oxide production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC₅₀ values of 6.57 ± 0.88 and 5.99 ± 1.20 μg/ml, respectively.