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The search for novel anticancer agents with more selectivity and lower toxicity continues to be an area of intensive investigation. The unique structural features of spirooxindoles together with diverse biological activities have made them privileged structures in new drug discovery. Among them, spiro-pyrrolidinyl oxindoles have been extensively studied as potent inhibitors of p53–MDM2 interaction, finally leading to the identification of MI-888, which could achieve rapid, complete and durable tumor regression in xenograft models of human cancer with oral administration and is in advanced preclinical research for cancer therapy. This review highlights recent progress of biologically active spirooxindoles for their anticancer potentials, mainly focusing on the discussions of SARs and modes of action. This article also aims to discuss potential further directions on the development of more potent analogues for cancer therapy. [ABSTRACT FROM AUTHOR]

Two novel constituents, named erigeronones A (1) and B (2), together with apigenin-7-O-β-galacturonide (3), quercetin-7-O-β-glucuronide (4), quercetin-3-O-β-galacturonide (5), and eriodictyol-7-O-β-glucuronide (6), were isolated from the whole grass of Erigeron breviscapus (Vant) Hand.-Mazz (Compositae). Their structures were established on the basis of spectral analyses and comparison with the literature data. Both new compounds 1 and 2 possess a γ-pyrone moiety that is rare in nature. Compound 1 showed significant protective effect on H2O2-injured human umbilical vein endothelial cells. [ABSTRACT FROM AUTHOR]

A novel cyclic peroxide, shuangkangsu (1), has been obtained from the water extract of the buds of Lonicera japonica (Thunb.). The structure was elucidated as 5,8-divinyl-1,4-dihydro-1,4-di-O-β-d-glucopyranosyl-2,3-dioxane (1) on the basis of the spectral data. Its absolute stereochemistry was determined to be (1S, 4S) by comparison of its CD curves with those of its optically pure analogs 2 and 3, which were synthesized from the phthalaldehyde. The absolute configurations of 2 and 3 were determined to be (1R, 4R) and (1S, 4S) by X-ray analysis and CD spectra, respectively. Compound 1 showed significant antiviral activities against influenza virus in chicken embryo and respiratory syncytial virus in cells. [ABSTRACT FROM AUTHOR]

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage. [ABSTRACT FROM AUTHOR]

Four new iridoid glycosides (1–4), rehmaglutosides L–O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1–6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri. [ABSTRACT FROM AUTHOR]

Seven new pentasaccharides (1–7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1–9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri. [ABSTRACT FROM AUTHOR]

The article presents work profile of Zhong-Jian Jia, professor at Lanzhou University in Lanzhou, China. It mentions that Jia perfumed several administration duties including the standing committee member of the Gansu Pharmaceutical Society. It states that she has trained several candidates of doctor of philosophy degree and postdoctoral students. It also mentions that Jia has won several honors and awards including "2nd-Class National Natural Science Prize."

A preface to the May 2015 issue of the journal is presented.

Two new iridal-type triterpenoids, named forrestins A and B (1 and 2), were isolated from Iris forrestii Dykes by comprehensive chromatographic methods. The structures of 1 and 2 were elucidated by interpretation of extensive spectroscopic data including 1D and 2D NMR and HRESIMS. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the author discusses the career of Professor Xiao-Tian Liang of the Chinese Academy of Sciences to whom this special issue is dedicated and which includes contributions from his close friends and students.

The novel iridals, polycycloiridals A-D, are isolated from the rhizomes of Iris tectorum. [ABSTRACT FROM AUTHOR]

Review: 84 refs. [ABSTRACT FROM AUTHOR]

As part of an ongoing project on Rehmannia species, three new pyridine alkaloides (glutinosines A − C), and one new iridoid analogue (rehmaglutin E), were isolated from the leaves of Rehmannia glutinosa. The structures of the new compounds were established by extensive spectroscopic analysis and electronic circular dichroism calculations. [ABSTRACT FROM AUTHOR]

Four new ionones and ionone glycosides (1–4) were isolated from the whole plant of Rehmannia piasezkii Maxim. Their planar structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. Compounds 1–4 were tested for their cytotoxicity against five human tumor cell lines and ability to inhibit LPS-activated NO production in the BV2 cell line. [ABSTRACT FROM AUTHOR]

Two new steroidal alkaloids peimisine-3-O-β-d-glucopyranoside (1) and puqiedinone-3-O-β-d-glucopyranoside (3), together with three known compounds peimisine (2), puqiedinone (4), and puqiedine (5), were isolated and characterized from the bulbs of Fritillaria unibracteata. Their structures were fully elucidated by spectroscopic and chemical methods. Compound 1 showed moderate protection effect on neurotoxicity of PC12 cell lines induced by rotenone. [ABSTRACT FROM PUBLISHER]

From the woods of Excoecaria agallocha , a new isopimarane-type diterpene, 3α,11β-dihydroxy- ent -isopimara-8(14),15-dien-2-one (1) and a new natural atisane-type diterpene, 16β-hydroxy- ent -atisan-3-one (2) were isolated together with three known compounds, ribenone (3), ent -labda-8(17),13 E -diene-3β,15-diol (4), and ent -3β-hydroxybeyer-15-ene-2,12-dione (5). Their structures were determined by spectral data and x-ray crystallography evidence. [ABSTRACT FROM AUTHOR]

The spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC. [ABSTRACT FROM AUTHOR]

Five new iridoids (1-5), jiohenrins A-E, together with sixteen known compounds (6-21), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data. [ABSTRACT FROM AUTHOR]

Eight new iridoids (1–8) and an ionone glucoside (9), together with 31 known compounds (10–40), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. [ABSTRACT FROM AUTHOR]

Two unprecedented tricyclic-iridal triterpenoids, belamcandanes A–B ( 1 – 2 ), have been isolated from the rhizomes of Belamcanda chinensis . The structures of 1 and 2 were assigned by interpretation of spectroscopic data including NMR and MS, and their absolute configurations were assigned by ECD calculation. Compounds 1 – 2 possess a spiro[4,5]decane core structure and a α-terpineol moiety, representing the first example of tricyclic-iridal triterpenoids. The plausible biogenetic pathway for 1 and 2 is also proposed. [ABSTRACT FROM AUTHOR]

Three new triterpenoids (1–3), together with four known triterpenoids (4–7), were isolated from the fruiting bodies ofGanoderma theaecolum. Their structures were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds4and6exhibited antitumor activities against H460 cells with IC50values of 22.4 and 43.1 μM, respectively. And the cytotoxic activities of compounds4and5against MDA-MB-231 cancer cell lines were assayed with IC50values of 49.1 and 75.8 μM, respectively. [ABSTRACT FROM AUTHOR]

Four new aristolochic acid derivatives aristchamic A ( 1 ), aristchamic B ( 2 ), aristochamic C ( 3a ), aristchamic D ( 3b ) and one new aristolactam aristolactam-CV ( 4 ), together with 10 known compounds ( 5 – 14 ), were isolated from the rhizomes of Aristolochia championii . Their structures were assigned by detailed analysis of MS and NMR spectroscopic data. All of the isolated compounds were evaluated for their cytotoxic activities against HCT-116, HepG2, BGC-823, NCI-H1650, and A2780 cell. Compound 1 exhibited significant cytotoxic activity against HCT-116, HepG2, BGC-823, and NCI-H1650, with IC 50 values of 0.50, 7.37, 2.66, and 0.75 μM, respectively. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the rhizomes ofIris tectorumresulted in the isolation and characterization of three new apocynin derivatives, apocynin-4-O-β-D-(6′-O-syringyl)glucopyranoside (1), scrophenoside C-7-ethyl ether (2,3), together with a new naturally occurring compound but known by synthesis, apocynin-4-O-β-D-xylopyranoside (4), and five known ones (5–9). Their structures were elucidated on the basis of spectroscopic data interpretation. [ABSTRACT FROM PUBLISHER]

Three new flavonoid glycosides (1–3) and one new aristololactamN-glycoside (4) were isolated from the rhizome ofAristolochia championii. The structures of compounds1–4were elucidated on the basis of their spectroscopic data and chemical evidence (UV, IR, HR-ESI-MS, 1D and 2D NMR). Their structures were determined as 8-(5-formyl-2-furanmethyl)-isorhamentin 3-O-robinobioside (1), 8-(5-methyl-2-furanoyl)-isorhamentin 3-O-robinobioside (2), 8-formylisorhamentin 3-O-robinobioside (3), and N-β-D-glucopyranosylaristololactam V (4), respectively. [ABSTRACT FROM PUBLISHER]

Phytochemical investigation on the whole plants of Iris japonica led to the isolation of four new aromatic glycosides. Their structures including the absolute configurations were determined by spectroscopic and chemical methods as (-)-4-hydroxy-3- methoxy acetophenone 4-O-β-d-{6-O-[4-O-(7R,8S)-(4-hydroxy-3- methoxyphenylglycerol- 8-yl)-3-methoxybenzoyl]}-glucopyranoside (1), (-)-4-hydroxy-3-methoxy acetophenone 4-O-β-d-{6-O-[4-O-(7S,8R)- (4-hydroxy-3-methoxyphenylglycerol-8-yl)-3-methoxybenzoyl]}- glucopyranoside (2), (-)-4-hydroxy-3-methoxy acetophenone 4-O-β-d-{6-O-[4-O-(7R,8R)-(4-hydroxy-3-methoxyphenylglycerol-8-yl)- 3-methoxybenzoyl]}-glucopyranoside (3), (-)-4-hydroxy-3-methoxy acetophenone 4-O-β-d-{6-O-[4-O-(7S,8S)-(4-hydroxy-3-methoxyphenylglycerol- 8-yl)-3-methoxybenzoyl]}-glucopyranoside (4), respectively. [ABSTRACT FROM AUTHOR]

Abstract One new nor sesquiterpenes, Schesesquiterpene (1), together with nine reported sesquiterpenes and nor sesquiterpenes (2 – 10) were obtained from Schefflera leucantha R.Vig. (Araliaceae). The structures were determined according to spectroscopic data analysis and chemical evidence. Noteworthily, Compound 7 was isolated as a new natural product, and other compounds (2 – 6 and 8 – 10) were obtained from the family Araliaceae for the first time. Graphical abstract Image 1 Highlights • One new nor sesquiterpenes was isolated from Schefflera leucantha R.Vig. • Nine known sesquiterpenes were obtained from Schefflera leucantha R.Vig. • Compound 7 was isolated as a new natural product. • Compounds 2 – 6 and 8 – 10 were obtained from the family Araliaceae for the first time. [ABSTRACT FROM AUTHOR]

Review: [85 refs. [ABSTRACT FROM AUTHOR]

A series of steroidal hybrids with different terminal bioactive scaffolds were synthesized using the molecular hybridization approach and further evaluated for their antiproliferative activity against several cancer cell lines of different origins using the MTT assay. The preliminary results indicated that compounds 12a–h with the terminal isatin motif were remarkably sensitive to SH-SY5Y cells, thereby exerting potent growth inhibition in vitro. This selectivity is possibly attributed to LSD1 inactivation (IC 50 = 3.18 μM). Besides, we also found that the chloro atom at the 7-position on the isatin core was beneficial for the activity through the SARs studies. Among this series, compound 12g showed the best inhibitory activity (IC 50 = 4.06 μM) against SH-SY5Y cells, which was comparable to that of 5-FU. Compound 12g arrested cell cycle at G2/M phase, induced apoptosis accompanied with decrease of mitochondrial membrane potential, and inhibited LSD1 potently (IC 50 = 3.18 μM). Docking studies showed that compound 12g formed interactions with surrounding amino acid residues and the steroid nucleus occupied the tubular hydrophobic cavity of the active site. Compounds 13–18 represented weak to moderate activity against the tested cancer cell lines. The steroidal dimer 20 and the structurally simplified non-steroidal dimer 21 were found to be devoid of the inhibitory activity. [ABSTRACT FROM AUTHOR]

Nine new compounds, together with 16 known analogs, were isolated from the whole plants ofRehmannia chingii. The structures of compounds1–9were elucidated on the basis of their spectroscopic data and chemical evidence. In addition, the new compounds were tested for their hepatoprotective activities against APAP-induced HepG2 cell damage and their ability to inhibit LPS-induced nitric oxide production in the murine microglia BV2 cell line. Compounds2and5exhibited pronounced hepatoprotective activities against APAP-induced HepG2 cell damage at a concentration of 10 μM, and compounds4and9showed moderate inhibitory activity against microglial inflammation factor with IC50values of 3.51 and 7.11 μM, respectively. [ABSTRACT FROM PUBLISHER]

Chemical examination of the ethanol extract of rhizomes of Iris tectorum led to the isolation and characterization of three new lignans, (7 R ,7′ R ,8 S ,8′ S )-5′-methoxy-neo-olivil (1a), (7 S ,7′ S ,8 R ,8′ R ) -5′-methoxy-neo-olivil (1b), (7 S ,7′ R ,8 S ,8′ S )-neo-olivil (2a), (7 R ,7′ S ,8 R ,8′ R )-neo-olivil (2b), (7 R ,7′ R ,8 S ,8′ S ,7′′ S ,8′′ S )- threo -neo-olivil-4′-O-8-guaiacylglycerol ether (3), together with six known ones (4–9). Among them, compounds 1 and 2 were found to be racemic mixtures, respectively, which were verified by chiral HPLC analysis, compound 3 was a new sesquineolignan. The structures were elucidated on the basis of extensive spectroscopic analysis. To our knowledge, this is the first report of lignan constituents isolated from I. tectorum . All compounds were evaluated for their cytotoxicity against five human tumor cell lines and none of them displayed significant toxicity in tested cell lines at a concentration of 10 μM. [ABSTRACT FROM AUTHOR]

A series of novel steroidal spirooxindoles 3a – h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C–C bonds, one C–N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5-FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC 50 values of 4.0 and 3.9 μM, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the twigs of Morus notabilis led to the isolation and characterization of two new flavonoids, notabilisin F (1) and notabilisin G (2). Their structures were elucidated on the basis of extensive spectroscopic analysis. [ABSTRACT FROM AUTHOR]

Seven new iridals ( 1 – 7 ), designated as iritectols C–F, 22-epiiritectol D, 22-epiiritectol E, 22-epiiritectol F together with three known analogues were isolated from the rhizomes of Iris tectorum . Among them, compounds 2 and 3 , 4 and 5 , and 6 and 7 were found to be three pairs of C-22 epimers, some of which were separated by chiral column chromatography. This is the first report on the occurrence of epimers of monocyclic iridals. Their structures were elucidated on the basis of extensive spectroscopic analysis. The isolates were evaluated for their cytotoxic activities against five human tumor cell lines. Compound 1 but not others exhibited moderate cytotoxic activities, with IC 50 values ranging from 4.1 to 9.8 μM. The structure–activity relationship of the tested compounds was briefly discussed. [ABSTRACT FROM AUTHOR]

The identification of novel anticancer agents with high efficacy and low toxicity has always been an intriguing topic in medicinal chemistry. The unique structural features of spirooxindoles together with diverse biological activities have made them promising structures in new drug discovery. Among spirooxindoles, CFI-400945 holds its promise as the first potent PLK4 inhibitor, the fumarate of CFI-400945 has entered phase I clinical trials for the treatment of solid tumors. However, questions remain as to whether PLK4 is the only relevant therapeutic target for CFI-400945. To highlight this significant progress of CFI-400945 in last two years, this review centers on the identification from a focused kinase library, structural optimizations and strategies involved, structure-activity relationships, modes of action, target validation, chemical synthesis and, more importantly, the kinase selectivity between PLK4 and other targets. [ABSTRACT FROM AUTHOR]

An unusual 5-C-methylated-dihydrobenzofuroisocoumarin, named multifidarin A (1), and two newent-kaurane diterpenoids, named multikauranes A (2) and B (3), together with three knownent-kaurane diterpenoids, were isolated from the whole plants ofPteris multifida. The structures of1–3were elucidated by spectroscopic methods. The cytotoxic activities of all new compounds were evaluated against five human tumor cell lines. A possible biosynthetic process for the formation of1is proposed. [ABSTRACT FROM PUBLISHER]

Three new iridal metabolites, iridojaponal A ( 1 ), B ( 2 ) and iridojaponal C ( 3 ) were isolated from the whole plants of Iris japonica . Their structures were elucidated on the basis of comprehensive spectroscopic data and chemical evidence. Iridojaponal A ( 1 ) and B ( 2 ) are the first examples of degraded iridals containing only 16 carbons. A plausible biogenetic pathway of 1 and 2 was also proposed. The absolute configuration at C-22 of 3 was determined by CD analysis accordance with Snatzke’s method. Furthermore, In vitro bioactivity assays, compounds 1 and 2 exhibited moderate hepatoprotective activities against APAP-induced HepG2 cell damage at a concentration of 10 μM. [ABSTRACT FROM AUTHOR]

Abstract: Seven new diterpenes, jiadifenoic acids J–P (1–7), two new sesquicarane sesquiterpenes, sesquicaranoic acids A and B (8 and 9), and four known compounds, were isolated from the stems of Illicium jiadifengpi. The trans-fused A/B ring junction in diterpenes was deduced from NMR data analysis and confirmed by single-crystal X-ray crystallography of 3. The absolute configurations of compounds 1 and 5 were determined using the Mo2(OAc)4-induced circular dichroism (ICD) method. Compounds 8 and 9 are a pair of C-10 epimers, and their absolute configurations were confirmed by analyzing their CD and ICD data. All of the isolated compounds were evaluated in vitro for their antiviral activities against Coxsackie virus B3 (CVB3). Among the isolated compounds, 4, 5, 7, 10, and 11 exhibited reasonable activity against CVB3, with IC50 values of 7.0–22.2 μmol/mL and selective index values (SI=TC50/IC50) of 49.3, 37.1, 31.3, 45.6 and 40.9, respectively. [Copyright &y& Elsevier]

Two new Diels–Alder adducts, yunanensins B and D (1and2), were isolated from the stem bark ofMorus yunanensis. Their structures were determined by spectroscopic analysis. Compounds1and2showed moderate antioxidant effects on liver microsomal lipid peroxidation induced by Fe2+-Cys system, with inhibitory ratios of 57.1% and 67.9% at a concentration of 10− 5 mol/l. [ABSTRACT FROM AUTHOR]

Two new Diels–Alder adducts, yunanensins B and D (1 and 2), were isolated from the stem bark of Morus yunanensis. Their structures were determined by spectroscopic analysis. Compounds 1 and 2 showed moderate antioxidant effects on liver microsomal lipid peroxidation induced by Fe2+-Cys system, with inhibitory ratios of 57.1% and 67.9% at a concentration of 10− 5 mol/l. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two series of novel steroidal spiro-oxindoles were efficiently synthesized. [•] Most of these compounds exhibited broad-spectrum antiproliferative activities. [•] Some of them were more potent than 5-Fu against four human cancer cell lines. [•] Compound 3g showed good antiproliferative activity against SMMC-7721 (IC50 =0.71μM). [•] Compound 3n showed cell cycle arrest at G2/M phase and induced early apoptosis. [Copyright &y& Elsevier]

Two new isoflavone glycosides, millesianins F (1) and G (2), along with 11 known ones (3–13) have been isolated from then-butanol extract of the vine stems ofMillettia dielsianaHarms. The structures of1and2were established as cladrastin 7-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranoside (1) and fujikinetin 7-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranoside (2) by means of spectroscopic analysis and chemical methods. Some isolates (compounds1,3,4,5,6, and11) were tested for their effects on the proliferation of hematopoietic progenitor cell, and the preliminary results showed that all of investigated compounds had moderate activities but not in dose-dependent manners. [ABSTRACT FROM PUBLISHER]

Four new ionone and ionone glycosides (1–4), and a new monoterpene (5), together with 10 known analogues (6–15), were isolated from the air-dried roots of Rehmannia glutinosa. The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Furthermore, in in vitro assays, compound 3 (10 μM) exhibited moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage. [ABSTRACT FROM AUTHOR]

Two new furostanol saponins ophiopogonins J (1) and K (2) were isolated from the fibrous roots ofOphiopogon japonicus. The structures of1and2were established as (25R)-26-O-[(β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl)]-14-hydroxy-furost-5,20(22)-diene 3-O-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside (1), and (25R)-26-O-[(β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl)]-furost-5,20(22)-diene 3-O-α-l-rhamnopyranosyl-(1 → 2)[(β-d-xylopyranosyl-(1 → 4)-β-d-glucopyranoside)] (2) on the basis of spectroscopic means including HRESIMS, 1D, and 2D NMR experiments. [ABSTRACT FROM PUBLISHER]

Abstract: A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer was designed, synthesized and evaluated for its cytotoxic activity against five human cancer cell lines and the cytotoxicity against human normal liver cell L-02. Compound 3 showed excellent cytotoxic activity and good selectivity between cancer and normal cells. Further mechanistic studies revealed that treatment of EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and time-dependent manner and induced apoptosis probably through the mitochondrial pathway accompanied with the decrease of mitochondrial membrane potential, activations of caspase-9/-3, cleavage of MDM2 as well as up-regulation of the expressions of p53 and Bax. [Copyright &y& Elsevier]

Highlights: [•] The steroidal dienamides were synthesized stereoselectively through a cascade aldol/cyclization process. [•] These compounds had moderate to excellent cytotoxic activities. [•] Some of these compounds were more potent than 5-fluorouracil. [•] Compound 3c represented excellent inhibition against MCF-7 (IC50 =0.76μM). [ABSTRACT FROM AUTHOR]

Hypodematine, isolated from Hypodematium sinense Iwatsuki as an alkaloid with a new skeleton, was synthesized via nine reaction steps, in which the synthesis of 2-aryl-1-benzazocines via Beckmann rearrangement of 5H-benzocyclohepten-5-one oxime mesylate in dry toluene is discussed. [ABSTRACT FROM AUTHOR]

Abstract: Two series of steroidal dienamides 4a–q and 5a–f were designed, synthesized and evaluated for cytotoxic activities against five human cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbon–carbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4a–q and 5a–f showed moderate to excellent cytotoxic activities with the IC50 values ranging from 0.1 to 40 μM and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC50 values less than 1 μM. Flow cytometry analysis demonstrated that compound 4c caused the cellular early apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner. [Copyright &y& Elsevier]

The chiroptical properties of an iridoid glycoside ajugol were fully investigated by quantum chemical calculations of specific optical rotation at the sodium D line ([α]D value), optical rotatory dispersion (ORD), and electronic circular dichroism (ECD) using time-dependent density functional theory (TDDFT). TDDFT calculations of the [α]D value and ORD of ajugol over the range of 365–633 nm were in good agreement with the experimental data. The predicted ECD spectrum of ajugol was also consistent with the experiment, showing a strong negative Cotton effect (CE) at around 190 nm and a weak positive CE at around 220 nm. Our results unambiguously determined the absolute configuration (AC) of the aglycone part of ajugol as (1S, 5R, 6R, 8S, 9S) and supported the generally accepted AC assignments of iridoid glycosides. Semi-empirical rule for the enol ether chromophore, basis set selection, and effect of glucose group on ECD spectra were also discussed in the case of ajugol. [ABSTRACT FROM AUTHOR]

Abstract: A simple and practical method for synthesis of the D-ring modified steroidal dienamides (4a–k) from the steroidal α,α-dicyanoalkene 3 and aldehydes via vinylogous aldol reaction was first reported. By using NaOAc as a base, the desired products were obtained in moderate to good yields in ethanol under mild conditions. All the synthesized steroidal dienamides are new and are currently being evaluated for their biological activities. [Copyright &y& Elsevier]

Two new tri-nor-eudesmane-type sesquiterpenoids were isolated from the roots ofInula racemosa, and their structures were elucidated as 8-oxo-tri-nor-eudesm-6-en-5α-ol (1) and tri-nor-eudesm-5-en-7β,8β-diol (2). The cytotoxic activity of compound1against five human cancer cell lines had been tested, but exhibited no cytotoxic activity. [ABSTRACT FROM PUBLISHER]