Three new terpenoids from the Eupatorium chinense

Three new terpenoids compounds (1–3) were obtained from ethyl acetate fraction, which was yielded from Eupatorium chinense’s ethanol extract. Their structures were determined on the basis of 1D and 2D NMR spectroscopy, including ¹H-¹H COSY, HMBC, HSQC and NOESY experiments. All of the isolated compounds were tested in vitro for their cytotoxic activities against the HepG₂, HGC-27 and MDA-MB-231 cancer cell lines.     

Two new resorcinol derivatives with strong cytotoxicity from the roots of Ardisia brevicaulis Diels

Two new resorcinol derivatives, 4-hydroxy-2-methoxy-6-[(8Z)-pentadec-8-en-1-yl]phenyl acetate (1) and 4-hydroxy-2-methoxy-6-pentadecylphenyl acetate (2), together with known compounds ardisiphenol D (3), 5-tridecylresorcinol (4), 5-pentadecylresorcinol (5), 5-[(8Z)-pentadec-8-en-1-yl]resorcinol (6), belamcandaquinones C and D (7 and 8, resp.), ardisicrenoside A, ardisiacrispin B, (22E)-24-ethyl-5α-cholesta-7,22-dien-3-one, and (22E)-24-ethyl-5α-cholesta-7,22-dien-3β-ol were isolated from the MeOH extract of the roots of Ardisia brevicaulis Diels. Their structures were determined by spectroscopic analysis including ESI- and EI-MS, and NMR data. Cytotoxicities of 1-4 against cell lines A549, MCF-7, and PANC-1 were tested in vitro by the MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method. Compounds 1-4 showed cytotoxic activity against all cell lines stronger than that of cisplatin against A549.     

A new species of Macaranga from the middle Miocene of Fujian,China and its significance

A well-preserved Macaranga leaf fossil from the middle Miocene Fotan Group of Zhangpu County, Fujian, South-eastern China is examined and described as a new species, Macaranga zhangpuensis Z.X. Wang et B.N. Sun sp. nov. The present fossil species represents the highest latitudinal distribution of a reliable Macaranga fossil in the world, and we present the first Macaranga fossil described with detailed cuticular characteristics from China. Based on the global palaeogeographic distribution of Macaranga, we infer that the genus probably originated during the Oligocene in Africa and spread from Africa to India and then to South Fujian, China, further into the Mariana Islands and finally into the Philippine Islands and Malaysia, leading to its present distribution. In addition, the new leaf material described herein is the first Macaranga fossil record with three leaf tips globally. This finding demonstrates that Macaranga with three leaf tips already existed during the Miocene in Fujian, South China, and it provides new information for understanding climatic changes between the Miocene and the present -day.     

Isolation, structure elucidation, and antioxidant evaluation of cydonioside A, an unusual terpenoid from the fruits of Cydonia vulgaris

A novel terpenoid, cydonioside A (1), was isolated from the fruits of Cydonia vulgaris Pers. Its structure and relative configuration were elucidated on the basis of in-depth spectroscopic analyses, including 2D-NMR experiments as well as MM+ calculations. Compound 1 was assayed for its radical-scavenging activity towards the DPPH radical and the superoxide radical anion (O2*-), as well as for its overall antioxidant activity, as assessed by the formation of a phosphomolybdenum complex.     

Surfactant-cobalt(III) complexes: synthesis, critical micelle concentration (CMC) determination, DNA binding, antimicrobial and cytotoxicity studies

A new class of surfactant-cobalt(III) complexes, cis-[Co(bpy)₂(C₁₁H₂₃NH₂)Cl]²⁺ (1) and cis-[Co(phen)₂(C₁₁H₂₃NH₂)Cl]²⁺ (2) (bpy = 2,2′-bipyridyl, phen = 1,10-phenanthroline), have been synthesized and characterized. The critical micelle concentration (CMC) values of these complexes in aqueous solution were obtained from conductance measurements. The specific conductivity data (at 298, 308, 318 and 328 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization . The interaction between these complexes and calf thymus DNA in aqueous solution was investigated adopting electronic absorption spectroscopy, emission spectroscopy and viscosity measurements. Results suggest that the two complexes can bind to DNA via groove binding, van der Waals interactions and/or electrostatic interactions. The complexes showed moderate antibacterial and antifungal activities against certain selected microorganisms. The cytotoxic activity of the complexes on HBL-100 human breast cancer cells was determined adopting MTT assay and specific staining techniques, which revealed that the viability of the cells thus treated was significantly decreased and the cells succumbed to apoptosis as seen in the changes in the nuclear morphology and cytoplasmic features. Furthermore, the influence of complexes on normal cell lines from green monkey kidney was also determined and the results indicate that the effect is small on inhibition of viability.     

Novel Oxaliplatin Derivatives with 1‐(Substituted Benzyl)azetidine‐3,3‐dicarboxylate Anions. Synthesis,Cytotoxicity, and Interaction with DNA

A series of oxaliplatin derivatives with (1R,2R)‐N¹‐alkyl‐1,2‐cyclohexane‐1,2‐diamine (alkyl=Bu or ⁱPr) as carrier ligands and 1‐(methoxy‐ or methyl‐substituted benzyl)azetidine‐3,3‐dicarboxylate anions as leaving groups were synthesized and spectrally characterized. Generally, Complexes 10 – 15 with an ⁱPr substituent at N(1) showed higher activities in vitro than carboplatin against MCF‐7 human breast carcinoma and A549 human non‐small‐cell lung cell lines, although they were less potent than oxaliplatin. The typical complex 14 exhibited cytotoxicity superior to that of carboplatin and comparable to that of oxaliplatin against two selected tumor cell lines. Additionally, agarose gel electrophoresis was applied to investigate the DNA‐cleavage ability of complex 14 , which demonstrated that it has a different mode of DNA distortion from that of oxaliplatin.     

Cytotoxic prenylated phenolic compounds from the twig bark of Garcinia xanthochymus

Three new hydroxylated xanthones with prenyl or geranyl substituents, compounds 1-3, were isolated from the twig bark of Garcinia xanthochymus, along with the four known compounds 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone (4), 1,3,5,6-tetrahydroxy-4,7,8-triprenylxanthone (5), garciniaxanthone E (6), and 6-prenylapigenin (7). Their structures were elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR as well as HR-MS experiments. All compounds showed moderate cytotoxicities against breast cancer (MDA-MB-435S) and lung adenocarcinoma (A549) cell lines, but lacked antifungal activity against Candida albicans.     

Cytotoxicity of new stilbenoids from Pholidota chinensis and their spin-labeled derivatives

Chemical investigation of the leave and stem of Pholidota chinensis Lindl has resulted in the isolation and characterization of three new stilbenoids. Their structures were established on the basis of spectroscopic evidence. A series of spin-labeled stilbene derivatives were synthesized. All of the new compounds were tested for cytotoxicity, and the results revealed that most of the spin-labeled stilbene derivatives showed superior cytotoxicity in vitro.     

Synthesis and characterization of a new macrocyclic copper(II) complex with an N-glycosidic pendant arm: in vitro cytotoxicity and binding studies with calf-thymus DNA

The new macrocyclic complex 2-amino-2-deoxy-N-[2-(1,3,5,8,11-pentaazacyclotridecan-3-yl)ethyl]-beta-D-glucopyranosylamine copper(II) dichloride (1a) was prepared and thoroughly characterized by various techniques. Molar-conductance measurements showed that 1a (and its Ni analogue 1b) are ionic in nature. On the basis of spectroscopic data, both complexes were assigned a square-planar geometry, and found to be highly stabile and hydrolytically robust in H2O over a wide range of pH, as confirmed by cyclic voltammetry (CV). The Cu(II) complex 1a was found to bind to CT-DNA, with a binding constant Kb of 2.4x10(3) M(-1), as derived by UV/VIS titration, and confirmed by CV, circular dichroism (CD), and viscosity measurements. DNA binding seems to occur mostly via H-bonding. In an in vitro antitumor MTT assay, 1a exhibited significant anticancer activity against the SY5Y and PC-12 cell lines, with an estimated IC50 value in the micromolar range for SYSY, similar to the standard drug 5-fluorouracil.     

New Thymol Derivatives and Cytotoxic Constituents from the Root of Eupatorium cannabinum ssp. asiaticum

Two new thymol (=5‐methyl‐2‐(1‐methylethyl)phenol) derivatives, 8,10‐didehydro‐9‐(3‐methylbutanoyl)thymol 3‐O‐tiglate ( 1 ) and 9‐O‐angeloyl‐8‐methoxythymol 3‐O‐isobutyrate ( 2 ), were isolated from the root of Eupatorium cannabinum ssp. asiaticum, together with six known compounds, 3 – 8 . The structures of 1 and 2 were determined through extensive 1D/2D‐NMR and MS analyses. Among the isolates, 9‐acetoxy‐8,10‐epoxythymol 3‐O‐tiglate ( 3 ) was the most cytotoxic, with IC₅₀ values of 0.02±0.01, 1.02±0.07, and 1.36±0.12 μg/ml, respectively, against DLD‐1, CCRF‐CEM, and HL‐60 cell lines. In addition, 10‐acetoxy‐9‐O‐angeloyl‐8‐hydroxythymol ( 4 ) and eupatobenzofuran ( 6 ) exhibited cytotoxicities, with IC₅₀ values of 1.14±0.16 and 2.63±0.22, and 7.63±0.94 and 2.31±0.14 μg/ml, respectively, against DLD‐1 and CCRF‐CEM cell lines.     

Some new nano-sized Fe(II), Cd(II) and Zn(II) Schiff base complexes as precursor for metal oxides: Sonochemical synthesis,characterization, DNA interaction,in vitro antimicrobial and anticancer activities

The complexes of Fe(II), Cd(II) and Zn(II) with Schiff base derived from 2-amino-3-hydroxypyridine and 3-methoxysalicylaldehyde have been prepared. Melting points, decomposition temperatures, Elemental analyses, TGA, conductance measurements, infrared (IR) and UV–Visible spectrophotometric studies were utilized in characterizing the compounds. The UV–Visible spectrophotometric analysis revealed 1:1 (metal-ligand) stoichiometry for the three complexes. In addition to, the prepared complexes have been used as precursors for preparing their corresponding metal oxides nanoparticles via thermal decomposition. The structures of the nano-sized complexes and their metal oxides were characterized by X-ray powder diffraction and transmittance electron microscopy. Moreover, the prepared Schiff base ligand, its complexes and their corresponding nano-sized metal oxides have been screened in vitro for their antibacterial activity against three bacteria, gram-positive (Microccus luteus) and gram-negative (Escherichia coli, Serratia marcescence) and three strains of fungus. The metal chelates were shown to possess more antimicrobial activity than the free Schiff-base chelate and their nano-sized metal oxides have the highest activity. The binding behaviors of the complexes to calf thymus DNA have been investigated by absorption spectra, viscosity mensuration and gel electrophoresis. The DNA binding constants reveal that all these complexes interact with DNA through intercalative binding mode. Furthermore, the cytotoxic activity of the prepared Schiff base complexes on human colon carcinoma cells, (HCT-116 cell line) and hepatic cellular carcinoma cells, (HepG-2) showed potent cytotoxicity effect against growth of carcinoma cells compared to the clinically used Vinblastine standard.     

Pencitrin and pencitrinol,two new citrinin derivatives from an endophytic fungus Penicillium citrinum salicorn 46

Two new citrinin derivatives, pencitrin (1) and pencitrinol (2), and a known compound citrinin (3), together with its two known dimers, penicitrinone A (4), penicitrinone E (5), were isolated from an endophytic fungus P. citrinum 46 derived from Salicornia herbacea Torr. by adding CuCl₂ into fermentation medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configurations of 1, 4, and 5 were determined by comparison of quantum chemical time-dependent density functional theory (TDDFT) calculated and electronic circular dichroism (ECD) spectra. Compound 1 exhibited potent cytotoxic activities towards A549 human lung cancer cells and HepG2 human liver cancer cells with IC₅₀ values of 23.73 ± 3.61 and 35.73 ± 2.15 μM, respectively, whereas compound 5 showed moderate cytotoxic activities towards A549 and HepG2 cancer cells with IC₅₀ values of 40.47 ± 4.52 and 53.57 ± 3.24 μM, respectively. The results from the current research highlighted the effectiveness and usefulness of the pipeline to discover novel bioactive fungal secondary metabolites by modification of the culture media.     

New bisamide compounds from the bark of Aglaia eximia (Meliaceae)

Two new bisamide compounds, eximiamide A (1) and eximiamide B (2) were isolated from the bark of Aglaia eximia (Meliaceae). The chemical structures of the new compound were elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds 1 and 2 exhibited cytotoxic activity against P-388 murine leukemia cells with IC₅₀ values of 7.6 and 8.5 μg/mL, respectively.     

Three new cassane diterpenes from the seeds of Caesalpinia sappan

Three new cassane furanoditerpenes, phanginins N–P (1–3), together with four known ones were isolated from the seeds of Caesalpinia sappan. Their structures were elucidated on the basis of spectroscopic analysis including HRESIMS, 1D and 2D NMR techniques. Evaluation of all the compounds for cytotoxicity against three human cancer cell lines (HepG-2, MCF-7 and HCT-8) showed insignificant results (IC₅₀ > 10 μM).     

Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L

Three new withanolide glycosides named daturametelins H-J (1-3), together with two known ones, daturataturin A (4) and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide (5), were isolated from the MeOH extract of the aerial parts of Datura metel L. (Solanaceae). Their structures were determined mainly by spectroscopic techniques including 2D-NMR (HMBC, HMQC, (1)H,(1)H-COSY, NOESY) and MS experiments. Compounds 1-5 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line. The nonglycosidic compound 5 exhibited the highest activity of the tested withanolides, with an IC(50) value of 3.2+/-0.2 microM (Table 3).     

Two new cycloartane-type triterpenoids and one new flavanone from the leaves of Dasymaschalon dasymaschalum and their biological activity

Two new cycloartane-type triterpenoids, 3β-hydroxy-21-O-acetyl-24-methylenecycloartane (3) and 3β,21-dihydroxy-24,31-epoxy-24-methylenecycloartane (4), one new flavanone, 7-hydroxy-6,8-dimethoxyflavanone (5), two new natural products, 2-hydroxybenzyl benzoate (7) and 2-phenyl-2-acetoxyethyl benzoate (8), and ten known compounds, 3β-hydroxy-24-methylenecycloartane (1), 3β,21-dihydroxy-24-methylenecycloartane (2), desmosdumotin B (6), artabotrene (9), (?)-senepoxide (10), (+)-crotepoxide (11), (?)-1,6-desoxypipoxide (12), rotundol (13), cassipourol (14) and (+)-spathulenol (15) were isolated from the leaves of Dasymaschalon dasymaschalum. The structures of the new compounds were elucidated by spectroscopic analysis and of the known compounds by comparison of their physical, UV, IR, ¹H and ¹³C NMR data with those of published compounds. Antimycobacterial, antiplasmodial and cytotoxic activities of the isolates, except 8 and 10 were evaluated. Compounds 1, 4, 5, 11, 12 and 15 exhibited potent cytotoxic activities against human lung cancer cell lines (NCI-H187) with respective IC₅₀ values of 4.67, 7.82, 1.85, 6.33, 3.07 and 6.68 μg/mL.     

Synthesis,characterization, cytotoxicity,and DNA binding of some new platinum(II) and platinum(IV) complexes with benzimidazole ligands

In this study, two Pt(II) and three Pt(IV) complexes with the structures of [PtL₂Cl₂] (1), [PtL₂I₂] (2), [PtL₂Cl₂(OH)₂] (3), [PtL₂Cl₂(OCOCH₃)₂] (4), and [PtL₂Cl₄] (5) (L = benzimidazole as carrier ligand) were synthesized and evaluated for their in vitro antiproliferative activities against the human MCF-7, HeLa, and HEp-2 cancer cell lines. The influence of compounds 1–5 on the tertiary structure of DNA was determined by their ability to modify the electrophoretic mobility of the form I and II bands of pBR322 plasmid DNA. The inhibition of BamH1 restriction enzyme activity of compounds 1–5 was also determined. In general, it was found that compounds 1–5 were less active than cisplatin and carboplatin against MCF-7 and HeLa cell lines (except for 1, which was found to be more active than carboplatin against the MCF-7 cell line). Compounds 1 and 3 were found to be significantly more active than cisplatin and carboplatin against the HEp-2 cell line.     

DNA-binding affinity,cytotoxicity, apoptosis,cell cycle inhibition and molecular docking studies of a new stilbene derivative

Stilbene derivatives have been found to possess promising anticancer activities against human cancer cell lines in vitro. In the present study, we have investigated cytotoxic, apoptosis induction and DNA binding activity of new stilbene derivative, (E)-1-(4-Chlorophenyl)-4,5-diphenyl-2-[4-(4-methoxystryl)phenyl]-1H-imidazol (STIM) on K562 chronic myeloid leukemia cell line. Via MTT assay STIM demonstrated cytotoxic activity against K562 cell line with IC₅₀ value of 150?µM. Apoptosis, as the mechanism of cell death, was evaluated by morphological study and flow cytometric analysis. In vitro DNA binding property of STIM has been studied by vital spectroscopic techniques, which indicated that STIM interact with ctDNA through groove binding mode and binding constant (K_b) was estimated to be 6.9?×?10⁴?M^?1. Docking studies revealed that hydrophobic is the most important interaction in STIM-DNA complex, and that the ligand (STIM) interacts with DNA via groove binding mode and the bindiyspng energy was calculated as ?13.37?kcal/mol. Taken together, the present study suggests that STIM exhibits anticancer effect on K562 cell line through the induction of apoptosis as well as cell cycle arrest at Sub-G1 phase and also can bind to double helix DNA in vitro.     

Analysis in vivo of antitumor activity, cytotoxicity and Interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride

Several metallic compounds recognized as potent antitumor agents, have been developed and tested in vivo and in vitro. In this work, we evaluated the toxic, therapeutic, and cytotoxic properties of the cis-dichloro-tetra-amine-ruthenium(III) chloride. Transplanted animals with Sarcoma 180 cells were treated with ruthenium(III) complex and injected i.p., at different time intervals. After the 15th day, tumoral postimplant, the animals were sacrificed and their lungs, kidneys, liver, and tumors were removed and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses. Interaction between the ruthenium complex and the DNA was also investigated. Besides being cytotoxic for the S180 cells, the metallic compound induced tumoral volume reduction and increased survival time of the animals treated. Serum levels of LDH, creatinine, and bilirubin increased, but no serious irreversible histopathological alterations were observed in the analyzed tissues. The compound did not cause anemia, but reduced the number of leukocytes in the treated animals. The absence of viable S180 cells, necrotic cells, and the presence of granulation tissue were observed in tumor tissue of treated animals. The Ru(III) complex, in the presence of the reduction agent, caused plasmid DNA to fragment. These results suggest that cis-RuCl(2)(NH(3))(4)Cl compound is a potent antitumoral drug in vitro and in vivo, which seems to involve binding to DNA molecule.     

Synthesis, cytotoxicity, and antitumor activity of lantadene-A congeners

Five new derivatives of the pentacyclic triterpenoid lantadene A (= 22beta-angeloyloxy-3-oxoolean-12-en-28-oic acid; 1) from the leaves of Lantana camara L. were synthesized, characterized, and screened for their cytotoxicities against four human cancer cell lines. The three most-potent compounds, i.e., 1, 4, and 6, with IC50 values in the range of ca. 20-29 microM, were further studied for their in vivo tumor-inhibitory potential upon oral administration in two-stage squamous cell carcinogenesis, using female Swiss albino mice, papilloma being induced by 7,12-dimethylbenz[a]anthracene (DMBA), and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). The results are discussed in terms of structure-activity relationship.