Cytotoxic arylbenzofuran and stilbene derivatives from the twigs of Artocarpus heterophyllus

Four new natural products, including three arylbenzofurans named heterophyllenes A-C (1–3), and one stilbene named heterophyllene D (4), together with twenty-one known compounds were isolated from the twigs of Artocarpus heterophyllus and their structures elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy. The cytotoxic activity of selected compounds against KB, MCF-7 and NCI-H187 cell lines was evaluated. Heterophyllene C (3) exhibited cytotoxicity against the MCF-7 cell line with an IC₅₀ value of 12.56 μM. Additionally, the known compounds norartocarpin and artocarpin showed cytotoxic activity against MCF-7 and KB cell lines with IC₅₀ values of 10.04 and 13.57 μM, respectively. Both compounds also displayed cytotoxicity against the NCI-H187 cell line with values of 14.78 and 14.21 μM, respectively.     

Visconata: A rare flavonol having long chain fatty acid from Dodonaea viscosa which inhibits Human neutrophil elastase (HNE)

A series of flavonoids were isolated from Dodonaea Viscosa and tested for inhibition of human neutrophil elastase (HNE), enzyme involved in inflammatory disorders. Isolated compounds were identified as a novel flavonol (1) along with eight known flavonoids (2–9). Novel flavonol, visconata (1) has a very rare skeleton having odd numbered long chain (C19) fatty acid, which was completely identified by mass fragmentation and 2D NMR analysis. All compounds (1–9) inhibited HNE in dose dependent manner with IC₅₀s ranging between 2.4 and 150 μM. Visconata (1) emerged to be the most potent compound with 2.4 μM of IC₅₀. In kinetic studies, compound (1) was observed to be reversible, noncompetitive inhibitor having K_i = 1.8 μM, whereas other flavonoids (2–9) displayed mixed type inhibition.     

Two acridones and two coumarins from the roots of Paramignya trimera

Two acridones, paratrimerins C (1) and D (2), and two coumarins, paratrimerins E (3) and F (4), were isolated from the CHCl₃ and EtOAc extracts of Paramignya trimera (Rutaceae), together with twelve known compounds (5–16). Their structures were elucidated on the basis of spectroscopic data. All isolated compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, and showed more potent inhibitory activity, with IC₅₀ values ranging from 14.6 to 112.2 μM, than the positive control acarbose (IC₅₀, 214.5 μM). The biosynthesis of the isolated coumarins and acridones was proposed.     

Antiplasmodial Securinega alkaloids from Phyllanthus fraternus: Discovery of natural (+)-allonorsecurinine

The chemical investigation of the antimalarial plant Phyllanthus fraternus G. L. Webster (Phyllanthaceae) resulted in the discovery of the Securinega alkaloid (+)-allonorsecurinine (1), previously reported as a synthetic compound, together with the known ent-norsecurinine (2), nirurine (3), bubbialine (4), epibubbialine (5) and the lignan phyllanthin (6). The structure and absolute configuration of the new compound were elucidated on the basis of extensive spectroscopic analysis, optical rotation, and GIAO NMR shift calculation followed by CP3 analysis. The antiplasmodial activity of these compounds was evaluated against chloroquine-resistant (W2) and -sensitive (3D7) strains of Plasmodium falciparum. Among them, ent-norsecurinine (2) and (+)-allonorsecurinine (1) showed the strongest activity (IC₅₀: 1.14 ± 0.32 and 2.57 ± 0.53 µM) respectively, against W2 but one of the weakest against 3D7.     

Diterpenoids from the aerial parts of Leonurus macranthus

One cis clerodane-type (1) and three highly oxygenated labdane-type diterpenes (2-4) were isolated from the aerial parts of Leonurus macranthus. Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus.     

Cereusitin A,a cyclic tetrapeptide from a Bacillus cereus strain isolated from the soft coral Antillogorgia (syn. Pseudopterogorgia) elisabethae

Two new compounds, cereusitin A (1), the tetrapeptide cyclo-(L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-leucyl-trans-4-hydroxy-L-proline and 4-(R)-hydroxysattabacin (2), along with the methyl, isopropyl, and propyl esters of p-hydroxybenzoic acid (3–5) were isolated from the organic extracts of the culture of the B. cereus RKHC-09 strain in two culture media (MOLP and B1), recovered from the sea fan Antillogorgia elisabethae (syn. Pseudopterogorgia elisabethae). Cereusitin A (1) showed mild antifungal activity against Colletotrichum gloeosporoides C26 (yam pathogen) but was inactive against Fusarium oxysporum f.sp. dianthi (carnation pathogen). The methyl and propyl esters of p-hydroxybenzoic acid (4 and 5) showed antimicrobial activity against S. aureus ATCC 33591 and S. cerevisiae, with an MIC of 2 μM.     

α-Glucosidase inhibitors from the stem of Mangifera reba

Two new neolignans, named rebaneolignan A (1) and B (2), were isolated from the stem of Mangifera reba (Anacardiaceae), together with six known compounds (3–8). Their structures were elucidated on the basis of NMR spectroscopic analysis and the absolute configurations of 1 and 2 were determined by NOESY and CD data. All isolated compounds were found to possess more potent inhibitory activity, with IC₅₀ values ranging from 28.5 to 162.8 µM, than the positive control acarbose (IC₅₀, 214.5 µM). Plausible biosynthetic pathways for the formation of 1 and 2 were proposed based on the oxidative β-5′ coupling reactions.     

Lanostane triterpenoids from fruiting bodies of the bracket fungus Fomitopsis feei

Three 24-methyl-lanostane triterpenoids, fomitopsins D–F (1–3), were isolated together with four known compounds (4–7) from fruiting bodies of the basidiomycete Fomitopsis feei. The structures were elucidated by spectroscopic analysis and chemical correlations, including the conversion of 1 into a mixture of 2 and 3 under acidic conditions. Compound 1 was previously isolated after conversion to a methyl ester derivative, however, the side-chain stereochemistry was not determined. Fomitopsins E (2) and F (3) exhibited activity against Bacillus cereus with MIC values of 6.25 μg/mL. On the other hand, fomitopsin D (1) showed activity against herpes simplex virus type 1 (HSV-1) with an IC₅₀ value of 17 μg/mL.     

A new cytotoxic salannin-class limonoid alkaloid from seeds of Azadirachta indica A. Juss

Azadiramide A (1), a new salannin-class limonoid alkaloid, inhibits growth of human breast cancer MDA-MB-231 cell line with IC₅₀ value of 2.70±0.63 μmol/L.     

Anti-inflammatory chromone alkaloids and glycoside from Dysoxylum binectariferum

Herein we report isolation of a new chromone alkaloid chrotacumine K (12) from fruits and a chromone glycoside schumaniofioside A (13) from leaves of Dysoxylum binectariferum Hook f. Schumaniofioside A is reported for the first time from Meliaceae family. Other known alkaloids isolated include rohitukine (1) and chrotacumine E (6). The structure of new alkaloid 12 was elucidated on the basis of extensive 1D and 2D NMR analysis, synthesis and chemical hydrolysis. Chemically, chrotacumine K (12) is a 3′-O-acetyl rohitukine which on chemical or enzymatic hydrolysis produces rohitukine. The new alkaloid 12 is also present in seeds and stem-barks of this plant. The glycoside schumaniofioside A (13) is present only in leaves, and in abundance (～1% w/w of dried leaves). The isolated compounds and extracts were evaluated for in vitro effect on the proinflammatory cytokines (TNF-α and IL-6) in human monocytic THP-1 cells. The alkaloid 12 displayed potent inhibition (57%) of TNF-α at 0.3 µM, and was non-toxic to THP-1 cells up to 40 µM, indicating its excellent therapeutic window. Furthermore, a nitrobenzoyl ester analog 15e showed better inhibition of IL-6 than parent natural product chrotacumine K.     

New compounds from the roots of Coriaria nepalensis

One new sesquiterpene lactone possessing novel variations in the structure, corialactone E (1), one new neolignan, coriarianeolignan A (2), together with three known apocarotenoids (3-5) and one known neolignan (6), have been isolated from a CHCl₃ extract of the roots of Coriaria nepalensis.     

New dammarane-type saponins from the leaves of Panax notoginseng

Two new triterpenoid saponins, notoginsenoside-Ng3 (1) and notoginsenoside-Ng4 (2), along with three known saponins (3-5), were isolated from a water extract of the leaves of Panax notoginseng. The absolute configuration of notoginsenoside Fa (3) with five sugars was confirmed by the single-crystal X-ray diffraction for the first time.     

New nitro-benzo[c]phenanthridine and indolopyridoquinazoline alkaloids from Zanthoxylum atchoum

The first phytochemical investigation of the roots of Zanthoxylum atchoum has led to the isolation of two new nitro-benzo[c]phenanthridine alkaloids 6-nitronitidine (1) and 6-nitro-8-methoxy-7,8-dihydronitidine (2), two new salts of indolopyridoquinazoline alkaloids 3-hydroxy-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (3) and its zwitterionic form 3-phenolate-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (4) along with 18 (5–22) known compounds. Their chemical structures were elucidated by spectroscopic analysis including 1D and 2D NMR and MS techniques. This is the first report of the nitro group on the biosynthesis of the natural benzo[c]phenantridine alkaloids. Compound 2 exhibited potent antibacterial activity against Staphylococcus aureus of MIC₅₀ = 4 μg·mL⁻¹.     

Two ring opened oxetane taxoids containing a C-20 benzoyloxy group from the roots of Taxus wallichiana Zucc.

Two new taxanes, named wallitaxane G (1) and H (2), were isolated from the roots of Taxus wallichiana (Taxaceae), together with nine known compounds (3?11). Their structures were elucidated on the basis of NMR spectroscopic analysis and the relative configurations of 1 and 2 were determined based on NOESY data. Wallitaxane H (2) showed the most potent α-glucosidase inhibitory activity, with an IC₅₀ value of 16.1 μM. Plausible biosynthetic pathways for the formation of 1 and 2 were proposed based on oxetane ring-opening and benzoyl migration.     

A new isocoumarin from metabolites of the endophytic fungus Alternaria tenuissima (Nees & T. Nees : Fr.) Wiltshire

A new isocoumarin,tenuissimasatin（1）,was isolated from metabolites of the endophytic fungus Alternaria tenuissima（Nees & T.Nees:Fr.） Wiltshire,which was isolated from the bark of Erythrophleum fordii Oliver,together with 11 known compounds（2- 12）.The structure and absolute configuration of 1 was determined by means of NMR and CD analysis.Compound 3 shows selective cytotoxic activity on human colon cancer cell HCT-8(IC₅₀ = 1.78μmol/L) by MTT test in vitro.Other compounds show no such activities(IC₅₀>10μmol/L).     

Cytotoxic gephyromycins from the Streptomyces sp. SS13I

Two new gephyromycins (1–2), belonging to angucyclinones, were identified from Streptomyces sp. SS13I. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and the structure of 1 was further elucidated by X-ray diffraction data. The absolute configurations of compounds 1–2 were evidenced by ECD calculations. To our best knowledge, Compounds 1–2 were the second reported gephyromycin-type angucyclinones. Compound 2 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.38 ± 0.47 μM.     

Cu2+-selective turn-on fluorescence signaling based on metal-induced hydrolysis of pyrenecarbohydrazide

We developed a simple Cu²⁺-selective turn-on fluorescence signaling probe based on the hydrolysis of 1-pyrenecarbohydrazide (1) to 1-pyrenecarboxylic acid. Probe 1 exhibited prominent fluorescence signaling of Cu²⁺ ions in a 10% aqueous Tris-buffered (pH 7.0) DMSO solution with a detection limit of 5.93 × 10^?8 M. Signaling with control compounds derived from pyreneacetic acid and pyrenebutyric acid showed that the fluorescence signal became less pronounced as the distance between the hydrazide functionality and the pyrene fluorophore increased. As a practical application, this probe was employed for the determination of Cu²⁺ in a simulated semiconductor wastewater.     

Synthesis,spectral characterization,theoretical, antimicrobial,DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand

Novel Cu(II) (1) and Zn(II) (2) complexes with 4-(1-(4-morpholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) (L) have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory) studies result confirms that, LMCT mechanism have been done between L and M(II) ions. The antimicrobial studies indicate that the ligand L and complexes 1 & 2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 & 2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 & 2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0). The K_b values of ligand L and complexes 1 & 2 are higher in acidic buffer at pH 4.0 (K_b = 2.42 × 10⁵, L; 2.8 × 10⁵, 1; 2.65 × 10⁵, 2) and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 & 2 have been studied. The in vitro anticancer activities results show that complexes 1 & 2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L.     

Efficient,collective synthesis and nitric oxide inhibitory activity of rubrolides E,F, R,S and their derivatives

An efficient first synthesis of biologically significant natural butenolides, rubrolides F (1f), R (1r), S (1s) & its 7″,8″-didehydro derivative (1sa), and 3″-bromo rubrolide (1fa) along with the synthesis of rubrolide E (1e) and its di-O-methyl derivative (1ea) is accomplished in a collective fashion from commercially available and inexpensive precursors in overall yields of 14–48.5%. Key features are Wittig-Horner reaction, SeO₂-induced tandem allylic hydroxylation/intramolecular cyclization and Knoevenagel condensation. Next, in their inhibitory activity towards nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity, all compounds displayed good inhibitory activity in a concentration-dependent manner. None of the compound exhibited notable cytotoxicity at the highest concentration (10 μM) and IC₅₀ values are found in the range from 8.53 to 17.85 μM.     

Design,synthesis and biological evaluation of quinazolin-4(3H)-one Schiff base conjugates as potential antiamoebic agents

In an effort to develop novel antiamoebic scaffolds having better efficacy than the standard drug metronidazole (IC₅₀ = 1.80 μM) used against Entamoeba histolytica, quinazolin-4(3H)-one Schiff base conjugates were synthesized and evaluated against HM1: IMSS strain of E. histolytica. Out of the thirteen compounds (S2-S14), six compounds (S2, S3, S4, S5, S6 and S11) were found to be better inhibitors than metronidazole and showed low cytotoxicity on HeLa cells, a cervical cancer cell line. The structure of intermediate compound S1 was confirmed by crystal structure studies.