In vitro cytotoxicity and druglikeness of pyrazolines and pyridines bearing benzofuran moiety

A series of pyrazolines and pyridines bearing benzofuran moiety (M1–M10) were synthesized for evaluation of theirin vitro cytotoxicity against MCF-7 and HepG2 cell lines. Furthermore, in silico drug-likeness study was carried out.The result of the cytotoxicity of M1–M10 showed that some compounds displayed cytotoxic activity against MCF-7and HepG2 cells. An assessment of in silico drug-likeness study of M1–M10 illustrates that some compounds showedan agreement to the Lipinski, Ghose, Veber, Egan, and Muegge rules with orally bioavailable.

Antimicrobial evaluation and molecular properties prediction of pyrazolines incorporating benzofuran and pyrazole moieties

A series of chalcones 3–5, 1H-pyrazolines 6–8, N-phenylpyrazolines 9–11, and N-acetylpyrazolines 12–14incorporating benzofuran and pyrazole moieties were synthesized and screened for their in vitro antimicrobial activityagainst some of pathogenic microorganisms. Among the screened compounds, 7 and 13 showed the most promisingantibacterial activity against Escherichia coli (G-). Compound 11 displayed broad spectrum antibacterial activityagainst Bacillus subtilis (G+). Moreover, compounds 10 and 4 were found to be the most potent antifungal agentagainst Candida albicans and Aspergillus niger, respectively. Also, the molecular properties prediction and druglikeness model score (DLS) of all the synthesized compounds were calculated by SwissADME and MolSoft websites,respectively. The two compounds 7 and 13 were found to be maximum DLS of 0.75 and 0.83, respectively.

A new benzofuran lignan from rhizomes of Polygonatum sibiricum / 中草药

Objective: To isolate and identify the chemical constituents from the rhizomes of Polygonatum sibiricum. Methods: The compounds were isolated and purified by various modern chromatographies, and their structures were identified by physiochemical properties and spectroscopic data. Results: Five compounds were isolated from the EtOH extract of the rhizomes of P. sibiricum, which were elucidated as polygonneolignanoside A (1), (+)-isolariciresinol-9'-O-β-D-glucopyranoside (2), trans-N-p- coumaroyltramine (3), 3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide (4), 3-(4-hydroxy-3-methoxyphenyl)- N-[2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide (5). Conclusion: Among them, compound 1 was a new benzofuran lignan, and compounds 2-5 were isolated from this plant for the first time.

A new benzofuran from Penicillium oxalicum, an endophytic fungus isolated from Pseudostellariaheterophylla / 中草药

Objective: To study the secondary metabolites of Penicillium oxalicum, an endophytic fungus isolated from the medicinal plant Pseudostellariaheterophylla. Methods: The secondary metabolites were isolated by silica gel, Sephadex LH-20 column chromatographies, and prep-TLC methods. Their structures were elucidated by using various spectroscopic techniques including HRESIMS and NMR spectra. Results: A benzofuran compound 5,7-dihydroxy-2-methylbenzofuran-3-carboxylic acid (1), five isocoumarins including (3R,4R)-(-)-4-hydroxymellein (2), O-methylmellein (3), acremonone G (4), decarboxycitrinone (5) and decarboxyhydroxycitrinone (6), four bisabolane-type sesquiterpenoids including (7S,11S)-(+)-12-acetoxysydonic acid (7), (S)-(+)-11-dehydrosydonic acid (8), sydonic acid (9) and 1-hydroxy-boivinianin A (10), as well as two meroterpenoid-type alkaloids decaturin D (11) and decaturinC (12) were isolated. Conclusion: Compound 1 is a new benzofuran compound and named as oxafuranone A, while compounds 2-6 and 10 are characterized from P. oxalicum for the first time.

N-Myristoyltransferases as antileishmanial targets: a piggyback approach with benzoheterocyclic analogues

Leishmaniasis is one of the neglected diseases that remain in need for pharmacological alternatives. In this context, N-Myristoyltransferases (NMT) arise as interesting targets to explore since they are involved in the co/post-translational processing of peptides which are responsible for host cell invasion. Studies that consider these enzymes as targets point out the potential of benzoheterocyclic compounds as inhibitors of Candida albicans's N-myristoyltransferase. Here we applied a combination of comparative binding site analysis and molecular docking studies based on a Piggyback approach in the search for new Leishmania major NMT ligands. Our results revealed that NMT enzymes from both pathogens present enough structural similarity to allow extrapolation of the knowledge available from C. albicans studies to develop new L. major NMT inhibitors. Molecular docking studies with benzoheterocyclic analogues indicate the potential of benzothiazole derivatives as L. major NMT ligands, giving rise to a completely new class of chemical compounds to be explored in the development of antileishmanial drugs.

Synthesis and antitumor activities of 8-aminobenzofuran3, 2-d pyrimidine derivatives / 中国药学杂志

OBJECTIVE: To synthesize the derivatives of 8-amino benzofuran[3, 2-d] pyrimidine and study their anticancer activiies. METHODS: The target compounds were synthesized through a series of reactions, and their anticancer activities in vitro were evaluated against COLO205, MCF-7 and K562 cell lines by MTT as assay. RESULTS: Nine title compounds were synthesized and confirmed by EI-MS, 1H-NMR and 13C-NMR. Compounds 2, 3d and 5c had good inhibition effect against COLO205, MCF-7 and K562 cells. The inhibition rates of compound 5c against COLO205, MCF-7 and K562 cells were 99.58%, 78.75% and 98.68% respectively at 10-4 mol · L-1. CONCLUSION: The anticancer activity of benzofuran[3, 2-d] pyrimidine derivatives is worthy of further study.

Saurusine B: A new lignan from Saururus chinensis / 中草药

Objective: To study the chemical constituents in the whole plants of Saururus chinensis. Methods: The chemical constituents were isolated by various column chromatographic methods. The structures of the compounds were elucidated on the basis of physiochemical properties and spectrascopic analysis. Results: Seven compounds were obtained and identified as trans-7, 8-dihydro-7-(3,4-methylenedioxyl)-phenyl-1'-(2-oxopropyl)-3'-methoxy-8-methylbenzofuran (1), 4-(3-methoxy-4-hydroxy) phenyl-3- methyl-3-buten-2-one (2), (+)-guaiacin (3), (+)-trans-1,2-dihydrodehydroguaiaretic acid (4), (-)-isolariciresinol-4-O-β-D-glucoside (5), isonectandrin B (6), and perseal F (7), respectively. Conclusion: Compound 1 is a new compound named as saurusine B, and compounds 2-7 are obtained from this plant for the first time.

Synthesis and anti-tumor activity in vitro of N-hetercycle substituted benzofuran derivatives / 中国药科大学学报

@#To discover the novel compounds with biological activity, N-hetercycle substituted derivatives were synthesized based on the structure of benzofuran. A series of novel N-hetercycle substituted benzofuran derivatives(2a-2j)were synthesized by the reaction of 2-(4′-florobenzoyl)benzofuran with N-heterocyclic compounds. And the structures were characterized by 1H NMR, 13C NMR and HRMS. Their anti-tumor activities were studied in vitro against a panel of human tumor cell lines(HeLa, A549 and H1975)by the MTT assay. The results indicate that compounds 2a, 2f and 2j are the most potent within this series of compounds against human tumor cell lines, showing that they are promising lead compounds for further structural modifications and biological evaluation.

17-methoxyl-7-hydroxyl-benzofuran chalcone alleviates myocardial ischemia/reperfusion injury via PI3K/Akt signal pathway / 中国药理学通报

Aim To investigate the effects of 1 7-me-thoxyl-7-hydroxyl-benzofuran chalcone(YLSC)on my-ocardial ischemia /reperfusion injury(MI /RI)by mod-ulating PI3K/Akt signaling pathway and the possible mechanisms.Methods Male SD rats were randomly divided into sham group,model group,YLSC group, wortmannin(WM)group and YLSC +WM group(n =8).The rat model of MI /RI was established by ligation of the left anterior descending artery for 30 min fol-lowed by loosening the ligature for 2 h.After reperfu- sion,blood samples were obtained to determine serum contents of CK-MB,LDH,NO and TNF-α.The pro-tein levels of total (t)-Akt,phosphorylated (p)-Akt and LC3-Ⅱ were detected by Western blot.Caspase-3,Beclin1 and eNOS mRNA expression was evaluated by FQ-PCR.Results YLSC pretreatment greatly re-duced serum levels of CK-MB,LDH and TNF-α,and elevated NO content.It also inhibited the expression of caspase-3,Beclin1 and LC3-Ⅱ,while enhanced p-Akt and eNOS expression.Conclusion YLSC protects the heart against MI /RI via inhibition of apoptosis and excessive autophagy,in which protective effect is regu-lated by activation of the PI3K/Akt pathway.

Neuroprotective and Antioxidant Effects of Novel Benzofuran-2-Carboxamide Derivatives

In the present study, we synthesized a series of novel 7-methoxy-N-(substituted phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and evaluated their neuroprotective and antioxidant activities using primary cultured rat cortical neuronal cells and in vitro cell-free bioassays. Based on our primary screening data with eighteen synthesized derivatives, nine compounds (1a, 1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the NMDA-induced excitotoxic neuronal cell damage at the concentration of 100 muM were selected for further evaluation. Among the selected derivatives, compound 1f (with -CH3 substitution at R2 position) exhibited the most potent and efficacious neuroprotective action against the NMDA-induced excitotoxicity. Its neuroprotective effect was almost comparable to that of memantine, a well-known NMDA antagonist, at 30 muM concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and 300 muM concentrations. These findings suggest that -CH3 substitution at R2 position and, to a lesser degree, -OH substitution at R3 position may be important for exhibiting neuroprotective action against excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain homogenate in moderate and appreciable degrees. Taken together, our structure-activity relationship studies suggest that the compound with -CH3 substitution at R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant activities. Further synthesis and evaluation will be necessary to confirm this possibility.

Content Determination of the 2 Lignan Components in Mongolian Medicine Compound Nutmeg-5 by HPLC / 中国药房

OBJECTIVE:To establish a method for the determining contents of 2 lignan components[dehydrodiisoeugenol and 2,3-dihydro-7-methoxy-2-(3,4-methylened ioxyphenyl)-3-methyl-5-(E)-propenyl-benzofuran(referred to“lignanoid 2”)]. METH-ODS:HPLC method was adopted. The column was Elite C18 with the mobile phase of water-methanol(gradient elution)at the flow rate of 1.0 ml/min;the detection wavelength was 225 nm and the column temperature was 30 ℃. The sample size was 20 μl. RE-SULTS:There was a good linear relationship between sample quantity and the peak area in the range of 0.202-2.02 μg(r=0.999 9) and 0.204-2.04 μg(r=0.999 9)for 2 lignan components. The RSD of precision,stability and repeatability tests were less than 2%with the average recovery of 101.54%(RSD=0.60%,n=6)and 99.43%(RSD=1.09%,n=6). CONCLUSIONS:The method is simple,sensitive and accurate,and can be used for the quantization determination of dehydrodiisoeugenol and lignanoid 2 in nut-meg-5.

Derivatives of 3H-spiro1-benzofuran-2, 1’-cyclohexanes: immunostimulants for veterinary use / Derivados de 3H-espiro1-benzofurano-2, 1’-ciclohexanos: inmunoestimulantes de uso veterinario

Four 3H-spiro1-benzofuran-2, 1’-cyclohexanes were synthesized from filifolinol, two of which are reported for the first time. Docking molecular studies were carried out to determine in silico whether these derivatives have similar immunostimulant activity to that reported for filifolinol, and its oxidation product, filifolinone. Through of the study of interactions of these compounds with the heterodimer of the protein present in teleost TLR1-TLR2, filifolinol, 3’-filifolinchloride and filifolinyl acetate shows similar interactions between them, allowing to predict that they would have similar immunostimulant activity, but different to filifolinone and filifolinane or that they would act by a different mechanisms.

Cuatro 3H-spiro1-benzofuran-2, 1'-ciclohexanos se sintetizaron a partir de filifolinol, dos de los cuales son reportados por primera vez. Se llevaron a cabo estudios de docking molecular para determinar in silico si estos derivados tienen actividad inmunoestimulante similar a la reportada para filifolinol y su producto de oxidación, filifolinona. A través del estudio de las interacciones de estos compuestos con el heterodímero de la proteína presente en teleósteos TLR1-TLR2 se estableció que el filifolinol, 3'-cloruro de filifolinilo y acetato de filifolinilo tienen interacciones similares con el heterodímero, lo que permite predecir que entre ellos tendrían una actividad simi- lar, pero diferente a la de la filifolinona y filifolinano o que estos últimos actuarían por diferentes mecanismos.

Chemical constituents in n-butanol extract from pine needles of Cedrus deodara / 中草药

Objective: To investigate the chemical constituents in the n-butanol extract of pine needles of Cedrus deodara. Methods: Chemical constituents were separated and purified by silica gel and Sephadex LH-20 chromatography column. The structures were elucidated on the basis of physicochemical properties and spectral data (1H-NMR, 13C-NMR, and DEPT). Results: The compounds were identified as 1-(4'-hydroxy-3'-methoxyphenyl)-2-[4″-(3-hydroxypropyl)-2″-methoxyphenoxy]-1, 3-propanediol (1), (7S, 8R)-9, 9'-dihydroxy-3, 3'-dimethoxy-7, 8-dihydro-benzofuran-1'-propanol base neolignan-4-O-β-D-glucoside (2), (7R, 8R)-3', 9, 9'- trihydroxy-3-methoxy-7, 8-dihydro-benzofuran-1'-propanol base neolignans-9-O-α-L-rhamnoside (3), (6R, 9R)-6-hydroxy-3-oxo-α- ionol-9-O-β-D-glucopyranoside (4), (6R, 9R)-3-oxo-α-ionol-9-O-β-D-glucopyranoside (5), shikimic acid butyl ester (6), quinic acid butyl ester (7), (6S, 9R)-6-hydroxy-3-oxo-α-ionol-9-O-β-D-glucopyranoside (8), 5-p-trans-coumaroylguinic acid (9), and (E)-1-O-p- coumaroyl-α-D-glucopyranoside (10). Conclusion: Compounds 1-7 are isolated from C. Trew for the first time.

A new benzofuran in Catalpa ovata / 中草药

Objective To study the chemical constituents in fruits of Catalpa ovata.Methods Various chromatographic techniques were used to separate and purify the constituents.Structures of the compounds were elucidated by physicochemical properties and spectral analysis (UV, IR, ESI-MS, 1H-NMR , 13 C-NMR , 1H- 1H COSY , HMQC, HMBC, NOESY, and CD).Results A compound was isolated and identified as 2(S)-(3′-hydroxy-5′-methoxy)-benz-3(S)-ethoxycarbonyl-6-trans-ethyl acrylate-8-methoxy-benzofuran.Conclusion This compound is a novel compound named as catalpafurxin.