Synthesis and Cytotoxicity of Some Thieno[2,3‐d]pyrimidine Derivatives

A series of compounds 5‐amino‐2‐ethylmercapto‐4‐phenyl‐6‐subistitutedthieno[2,3‐d]pyrimidines ( 8a–d ), 4‐chloro‐7‐ethylmercapto‐9‐phenylpyrimido[5′,4′:4,5]thieno[3,2‐d]triazine ( 9 ), and 2‐ethylmercapto‐8‐oxo‐4‐phenyl‐7‐(4‐chlorophenyl)pyrimido [4′,5′:4,5]thieno[2,3‐d]pyrimidine ( 10 ) were synthesized and their structures were confirmed by ¹H NMR , ¹³C NMR, and MS . All compounds were evaluated for their IC₅₀ values against three cancer cell lines (MCF ‐7, HUH ‐7 and BHK ) and WISH cells. The IC₅₀ of compound ( 8d ) was calculated for each cell line. Interestingly, the IC₅₀ for the normal human amnion WISH cell line was much higher (723 µg/mL) than those found for the tumor cell lines BHK (17 µg/mL), HUH ‐7 (5.8 µg/mL), and MCF ‐7 (8.3 µg/mL). The proliferation inhibition of normal (WISH ) and tumor (BHK , HUH ‐7, and MCF ‐7) cells by compound ( 8d ) was investigated using MTT assay, and the IC₅₀ was calculated after 48 h of treatment for each cell line.     

Synthesis,Crystal Structures and Anticancer Activity of the New Chiral Mono‐ and Dinuclear Palladium(II) Complexes derived from (S)‐(‐)‐(1‐phenylethylimino)benzylphenylketone

The enantiopure ketoimine of benzil – the ( S )‐(‐)‐(1‐phenylethylimino)benzyl phenyl ketone ( 1 ) obtained under microwave irradiation in solvent‐free conditions – reacts with Na₂[PdCl₄] to give the new chiral mono‐ and dinuclear Pd‐complexes 2 and 3 , which have been partly characterized by IR, ¹H and ¹³C NMR spectroscopies along with MS‐FAB⁺ spectrometry. The crystal and molecular structures of both complexes has been fully confirmed by single‐crystal X‐ray studies. On the other hand, investigations in vitro of 2 and 3 have displayed growth inhibition against different classes of cancer: leukemia (K‐562 CML), colon cancer (HCT‐15), cancer breast (MCF‐7), central nervous system (U‐251 Glio) and prostate cancer (PC‐3) cell lines.     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).     

Synthesis and Cyclization of 8‐Formyl‐2‐(phenoxymethyl)quinoline‐3‐carboxylic Acids

A facile synthesis of a series of new quinoline‐8‐carbaldehyde compounds, namely 8‐formyl‐2‐(phenoxymethyl)quinoline‐3‐carboxylic acids ( 4a – 4h ) and 13‐oxo‐6,13‐dihydro[1]benzoxepino[3,4‐b]quinoline‐8‐carbaldehyde ( 5a – 5g ) is described, involving the one‐pot synthesis reaction of ethyl 2‐(chloromethyl)‐8‐formylquinoline‐3‐carboxylate ( 3 ) with substituted phenols followed by the intramolecular cyclization reaction via the treatment with polyphosphoric acid (PPA). Quinoline‐8‐carbaldehydes 4a – 4h and 5a – 5g are novel and their structures were supported by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis.     

Synthesis,characterization and cytotoxic activity of 5,10,15,20‐tetrakis[4‐(triorganostannyloxy)phenyl]porphyrins

5,10,15,20‐Tetrakis[4‐(triorganostannyloxy)phenyl]porphyrins, (R₃SnO)₄TPP [2, R = Cy (a), Ph (b), PhC(CH₃)₂CH₂ (c)], have been synthesized by the condensation of 4‐(triorganostannyloxy)benzaldehyde, 4‐(R₃SnO)C₆H₄CHO (1), with pyrrole in the presence of BF₃ followed by oxidation by p‐chloranil and characterized by means of elemental analysis, IR, UV–visible and NMR (¹H, ¹³C and ¹¹⁹Sn) spectra. The results of X‐ray single‐crystal diffraction show that 1a and 1b possess a trans‐C₃SnO₂ trigonal bipyramidal geometry with the axial positions occupied by the phenolate oxygen and formyl group oxygen of an adjacent molecule and form a one‐dimensional zigzag chain. In 2a, the macrocyclic core of the porphyrin is coplanar and each tin atom possesses a distorted tetrahedral geometry. These compounds (1 and 2) have potent in vitro cytotoxic activity against two human tumor cell lines – CoLo205 and MCF‐7 – and the activity decreases in the order Ph > Cy > PhC(CH₃)₂CH₂ for the R group bound to tin. Copyright © 2013 John Wiley & Sons, Ltd.     

Effect of lipophilicity of wingtip groups on the anticancer potential of mono N‐heterocyclic carbene silver(I) complexes: Synthesis,crystal structures and in vitro anticancer study

A series of symmetrically n ‐alkyl‐substituted mono benzimidazolium salts with steady increase in n ‐alkyl chain length have been prepared by stepwise N ‐alkylation resulting in salts ( 1 – 8 ). The mono N‐heterocyclic carbene (NHC)–Ag(I) complexes ( 9 – 16 ) derived from the respective salts were readily accessible by in situ deprotonation using Ag₂O. All the salts and the complexes were characterized using Fourier transform infrared, ¹H NMR, ¹³C NMR and elemental analyses. Furthermore, the structures of salts 3 and 7 and complex 16 were elucidated using X‐ray crystallography, which established that this mono NHC–Ag(I) complex has a linear bis‐carbene arrangement (C₂–Ag). The proligands and the respective Ag(I) complexes were studied for their in vitro anticancer potential against human colon cancer cell line (HCT‐116) using 5‐fluorouracil as a standard. From the IC₅₀ values of all the tested compounds, it can be postulated that there is an influential relationship between the increase in chain length of the wingtip n ‐alkyl groups and the anticancer potential. The proligands 4 – 8 and their respective complexes 12 – 16 with long n ‐alkyl chain lengths (n  = 6–10) showed better IC₅₀ values (0.3–3.9 μM) than the standard drug with the complexes displaying markedly better antiproliferation activity against HCT‐116 cell line than the respective proligands and the standard drug (IC₅₀ = 10.2 μM).     

1,1‐Organoboration of bis(trimethylstannyl)ethyne with trimethylsilyl‐ and dimethylsilyl‐dialkylboryl‐substituted alkenes: organometallic‐substituted allenes

The reactions of bis(trimethylstannyl)ethyne, Me₃Sn–C?C–SnMe₃ ( 4 ), with trimethylsilyl‐ or dimethylsilyl‐dialkylboryl‐substituted alkenes 1 – 3 afford organometallic‐substituted allenes 5 , 6 and 8 , 9 in high yield. In the case of (E)‐2‐trimethylsilyl‐3‐diethylboryl‐2‐pentene ( 1) , a butadiene derivative 7 could be detected as an intermediate prior to rearrangement into the allene. All reactions were monitored by ²⁹Si and ¹¹⁹Sn NMR, and the products were characterized by an extensive NMR data set (¹H, ¹¹B, ¹³C, ²⁹Si, ¹¹⁹Sn NMR). Copyright © 2003 John Wiley & Sons, Ltd.     

New Pyrrole Alkaloids with Bulky N‐Alkyl Side Chains Containing Stereogenic Centers from Lycium chinense

Four new pyrrole alkaloids, methyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]propanoate ( 1 ), methyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]‐3‐(4‐hydroxyphenyl)propanoate ( 2 ), dimethyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]butanedioate ( 3 ), and dimethyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]pentanedioate ( 4 ), were isolated from the AcOEt extract of the fruits of Lycium chinense Miller (Solanaceae). The stereogenic center C(2) in the bulky N‐alkyl side chain in each of 1 – 4 seems to hold the H‐atoms of nearby CH₂ groups, CH₂(7′) and CH₂(3) (if R≠H), leading to two different chemical shifts in the ¹H‐NMR spectrum due to their diastereotopic characteristics. In the ¹H‐NMR data of each of 2 – 4 , the enhancement of H? C(2) signal was inhibited by the R group, probably due to steric hindrance, and its chemical shift was influenced by the anisotropy effect. The structures of 1 – 4 were elucidated by analysis of various spectroscopic data, including 1D‐ and 2D‐NMR.     

Preparation and Structures of 2‐Substituted 5‐Benzyl‐3‐methylimidazolidin‐4‐one‐Derived Iminium Salts,Reactive Intermediates in Organocatalytic Transformations Involving α,β‐Unsaturated Aldehydes

Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde‐derived iminium salts 12 – 14 (Scheme 3 and Table 3) are reported. The X‐ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H‐NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis,in vitro Antimicrobial,and Cytotoxic Activities of New 1,3,4‐Oxadiazin‐5(6H)‐one Derivatives from Dehydroabietic Acid

A series of new 1,3,4‐oxadiazin‐5(6H)‐one derivatives ( 6a–n ) of dehydroabietic acid were designed and synthesized as potential antimicrobial and antitumor agents. Their structures were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. All the title compounds were evaluated for their antimicrobial activity against four bacterial and three fungal strains using the serial dilution method. Among them, compound 6e showed the highest antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 1.9 μg/mL. In addition, the in vitro cytotoxic activities of the title compounds were also assayed against three human carcinoma cell lines (MCF‐7, SMMC‐7721, and HeLa) through the MTT colorimetric method. As a result, compounds 6b , 6g , 6k, and 6m exhibited significant inhibition against at least one cell line with IC₅₀ values below 10 μM. Compound 6m was especially found to be the most potent derivative with IC₅₀ values of 2.26 ± 0.23, 0.97 ± 0.11, and 1.89 ± 0.31 μM against MCF‐7, SMMC‐7721, and HeLa cells, respectively, comparable to positive control etoposide.     

Synthesis and Structural Characterization of Metal Complexes of 2‐Formylpyrrole‐4N‐ethylthiosemicarbazone (4 EL1) and 2‐Acetylpyrrole‐4N‐ethylthiosemicarbazone (4 EL2)

The reactions of ⁴N‐ethyl‐2‐[1‐(pyrrol‐2‐yl)methylidene(hydrazine carbothioamide ( 4 EL₁ ) and ⁴N‐ethyl‐2[1‐(pyrrol‐2‐yl)ethylidene(hydrazine carbothioamide ( 4 EL₂ ) with Group 12 metal halides afforded complexes of types [M(L)₂X₂] (M = Zn, Cd; L = 4 EL₁, 4 EL₂; X = Cl, Br, I; 1 – 6 , 14 – 19 ) and [M(L)X₂] (M = Hg; L = 4 EL₁, 4 EL₂; X = Cl, Br, I; 7 – 9 , 20 – 22 ). In addition, reaction of 4 EL₁ with salts of Cu^II, Ni^II, Pd^II and Pt^II afforded compounds of type [M(4 EL₁–H)₂] ( 10 – 13 ). The new compounds were characterized by elemental analysis, FAB mass spectrometry, IR and electronic spectroscopy and, for sufficiently soluble compounds, ¹H, ¹³C and, when appropriate, ¹¹³Cd or ¹⁹⁹Hg NMR spectrometry. The spectral data suggest that in their complexes with Group 12 metal cations, both thiosemicarbazones are neutral and S‐monodentate; and for [Zn(4 EL₁)₂I₂] ( 3 ), [Cd(4 EL₁)₂Br₂] ( 5 ) and [Hg(4 EL₁)Cl₂]₂ ( 7 ) this was confirmed by X‐ray diffractometry. By contrast, in its complexes with Cu^II and Group 10 metal cations, 4 EL₁ is monodeprotonated and S,N‐bidentate, as was confirmed by X‐ray diffractometry for [Ni(4 EL₁–H)₂] ( 11 ) and [Pd(4 EL₁–H)₂] ( 12 ).     

1, 9‐Dihydro‐purine‐6‐thione Derivatives of the d8–d10 Metal Ions (PdII,PtII, and CuI): Synthesis,Spectroscopy, and Structures

Reaction of 1, 9‐dihydro‐purine‐6‐thione (puSH₂) in presence of aqueous sodium hydroxide with PdCl₂(PPh₃)₂ suspended in ethanol formed [Pd(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 1 ). Similarly, complexes [Pd(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 2 – 4 ) {L‐L = dppm (m = 1) ( 2 ), dppp (m = 3) ( 3 ), dppb (m = 4) ( 4 )} were prepared using precursors the [PdCl₂(L‐L)] {L‐L = Ph₂P–(CH₂)_m–PPh₂}. Reaction of puSH₂ suspended in benzene with platinic acid, H₂PtCl₆, in ethanol in the presence of triethylamine followed by the addition of PPh₃ yielded the complex [Pt(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 5 ). Complexes [Pt(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 6 – 8 ) {L‐L = dppm ( 6 ), dppp ( 7 ), dppb ( 8 )} were prepared similarly. The 1, 9‐dihydro‐purine‐6‐thione acts as N⁷,S‐chelating dianion in compounds 1 – 8 . The reaction of copper(I) chloride [or copper(I) bromide] in acetonitrile with puSH₂ and the addition of PPh₃ in methanol yielded the same product, [Cu(κ²‐N⁷,S‐puSH)(PPh₃)₂] ( 9 ), in which the halogen atoms are removed by uninegative N, S‐chelating puSH^– anion. However, copper(I) iodide did not lose iodide and formed the tetrahedral complex, [CuI(κ¹‐S‐puSH₂)(PPh₃)₂] ( 10 ), in which the thio ligand is neutral. These complexes were characterized with the help of elemental analysis, NMR spectroscopy (¹H, ³¹P), and single‐crystal X‐ray crystallography ( 3 , 7 , 8 , 9 , and 10 ).     

The synthesis,structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, ¹H–¹H correlation spectroscopy (COSY) and ¹H–¹³C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC₅₀ value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC₅₀ values than that found for the clinically employed anticancer drug cisplatin (IC₅₀ = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

Discovery of New S‐Glycosides and N‐Glycosides of Pyridine‐biphenyl System with Antiviral Activity and Induction of Apoptosis in MCF7 Cells

Glycosylation of small molecule‐based drugs can dramatically improve the biological activities of the parent scaffold. In the current study, S‐glycosides and N‐glycosides of polyfunctionalized pyridine‐biphenyl system tethered with benzotriazole moiety were designed and synthesized. S‐Glycosides of pyridine‐2‐thione derivatives 5a – h and N‐glycosides of pyridine‐2‐one derivatives 9a , b were synthesized by a facile, convenient, and high‐yielding procedure. The epimers glucose and galactose, acetylated or deacetylated, were used to form the glycone part. The structures of these compounds were confirmed by microanalysis and spectroscopic data (IR, ¹ H–NMR, and ¹³C‐NMR). The anticancer activities of the target compounds, in comparison with standard cisplatin, were assessed by MTT assay against MCF7 cell line. Compounds 4f , 4g , 5f , and 5h exhibited the highest cytotoxic effect on MCF7. The anticancer effect of these four compounds induced the apoptosis as evident by the up‐regulated expression of the apoptotic genes Bax and p53 and down‐regulated expression of the anti‐apoptotic gene BCl₂. S‐Glycoside derivatives are more active than N‐glycosides. Moreover, the nontoxic doses of the tested compounds were evaluated in MA104, FRHK4, BGM, Hep2, and Vero cells. Compounds 4a – d and 5a – d were also evaluated for their antiviral effect against HSV‐1, HAV, and rotavirus Wa strain. The compounds' results showed less, moderated, and high antiviral activities. The docking study for these compounds with MDM2 revealed that deacetylated galactose is important for binding with the receptor as it facilitates the formation of hydrogen bond in the receptor. Rapid overlay of chemical structures analysis was employed to understand the compounds' similarity on the basis of their shape structure using the Tanimoto scores.     

Synthesis and structure of novel spirosilanes. Combination of 1,2‐hydroboration and 1,1‐organoboration

The reaction of tetra(alkyn‐1‐yl)silanes Si(C?C‐R¹)₄ 1 [R¹ = ^tBu ( a ), Ph ( b ), C₆H₄‐4‐Me ( c )] with 9‐borabicyclo[3.3.1]nonane (9‐BBN) in a 1:2 ratio affords the spirosilane derivatives 5a – c as a result of twofold intermolecular 1,2‐hydroboration, followed by twofold intramolecular 1,1‐organoboration. Intermediates 3a–c , in which two alkenyl‐ and two alkyn‐1‐yl groups are linked to silicon, were identified by NMR spectroscopy. The molecular structure of the spiro compound 5c was determined by X‐ray analysis, and the solution‐state structures of products and intermediates follow conclusively from the consistent NMR spectroscopic data sets (¹H, ¹¹B, ¹³C and ²⁹Si NMR). Copyright © 2008 John Wiley & Sons, Ltd.     

Formyl phloroglucinol meroterpenoids from Eucalyptus tereticornis and their bioactivities

Five new formyl phloroglucinol meroterpenoids (FPMs), eucalteretials A?E (1–5), along with eight known analogues (6?13), were isolated from the twigs and leaves of Eucalyptus tereticornis. Their structures were established mainly by analysis of comprehensive spectroscopic data, and their absolute configurations were determined by electron circular dichroism (ECD) calculation. Within FPMs, both 1 and 2 are rare adducts of formyl phloroglucinol moiety and germacrene unit with different coupling patterns, respectively. Compound 3 exhibited significant cytotoxicity against HCT116?cell line with an IC₅₀ value of 4.76?μM. In addition, 5 and 9 were proved to be rare topoisomerase I (Top1) inhibitors.     

New Briaranes from the South China Sea Gorgonian Junceella fragilis

Three new briarane diterpenes, junceellonoids C–E ( 1 – 3 ), along with six known briaranes, junceellin A ( 4 ), praelolide ( 5 ), and junceellolides A‐D ( 6 – 9 ), were isolated from the EtOH/CH₂Cl₂ extracts of the South China Sea gorgonian coral Junceella fragilis. The structures of 1 – 3 were established by extensive spectroscopic analysis, including 1D‐ and 2D‐NMR data. Compounds 1 and 2 exhibited mild cytotoxicity against human galactophore carcinoma (MDA‐mB‐231 and MCF‐7) cells at the concentration of 100 μM .     

New Cytotoxic Meroterpenoids from the Plant Endophytic Fungus Pestalotiopsis fici

Pestalofones I – K ( 1 – 3 ), three new dimeric meroterpenoids with 2‐(7‐benzoyl‐2,3‐dihydrobenzofuran‐2‐yl)‐1‐phenylethan‐1‐one (in 1 ) and 2‐(7‐benzoyl‐2,3‐dihydrobenzofuran‐2‐yl)‐1‐(3,8‐dioxatricyclo[5.1.0.0^2,4]oct‐4‐yl)ethan‐1‐one (in 2 and 3 ) skeletons, were isolated from the solid cultures of the plant endophytic fungus Pestalotiopsis fici. The structures of 1 – 3 were elucidated by NMR experiments. Compound 1 was found to be present as a racemic mixture. The absolute configurations of 2 and 3 were deduced by analogy to the previously isolated metabolites pestalofones G and H ( 4 and 5 ) from the same fungus. Biogenetically, compounds 1 – 3 are derived from the same precursors (co‐isolated compounds 9 and 10 ) as the previously isolated compounds 4 – 8 . Compounds 2 and 3 showed weak cytotoxic activities against four human tumor cell lines T24, HeLa, A549, and MCF‐7.