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[Display omitted] • Fourteen alkaloids were isolated from Acorus calamus. • Compound 1 was a new alkaloid and compound 3 was a new natural product. • The absolute configurations of compounds 1 – 2 were deduced by induced CD spectra. • Compound 4 exhibited significant PPARα/γ, and glucokinase-activating activities. • Molecular docking of compound 4 bound with PPARα, PPARγ, and GK was carried out. Fourteen alkaloids of diverse carbon skeletons, including a new compound 2 R -4-(5′-methyl-pyrazin)-2-yl-but-3-ene-1,2-diol (1) and a new natural product methyl 2-(4-hydroxyphenyl)acetyl glycinate (3), were isolated from the ethanol extract of Acorus calamus Linn. rhizomes. Their structures were determined based on extensive spectroscopic analyses and comparing of the literature data. Compounds 1 – 5 were evaluated for their in vitro PPARα, PPARγ, and glucokinase-activating activities, and neotatarine (4) exhibited significant PPARα and PPARγ activating activities at 10−6 mol/L, and it also exhibited significant glucokinase activating activities at 10-5 mol/L. Furthermore, molecular docking of compound 4 bound with PPARα, PPARγ, and GK was carried out to investigate some possible structural insights into the potential binding patterns. [ABSTRACT FROM AUTHOR]

• Compounds 1 and 2 have interesting nor -iridal skeleton that are previously undescribed. • This is the first report on the chemical constituents of Iris wattii Baker. • Compound 1 showed a certain degree of inhibitory effect on the PTP1B. Two unprecedented C 16 nor -iridal esters (1 ― 2), named iriwattin A (1) and iriwattin B (2), along with one known iridal ester and two known iridal-type triterpenoids were isolated from Iris wattii Baker by comprehensive chromatographic methods. The structures of 1 ― 2 were elucidated by interpretation of extensive spectroscopic analyses (1D and 2D NMR, ESI- and HRESI-MS). The two new compounds have interesting nor-iridal skeleton that are previously undescribed, and therefore constitute a new class of C 16 nor -iridal esters. Furthermore, compounds 1 and 2 were tested for their in vitro inhibitory activities against α -glucosidase and protein tyrosine phosphatase 1B (PTP1B). Compound 1 showed a certain degree of inhibitory effect on the PTP1B enzyme, with 52.0% inhibition. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the ethanol extract of whole plants of Iris japonica led to the isolation of three new and eight known analogues of flavonoid glycosides. The newly isolated structures were determined by spectroscopic and chemical methods as tectorigenin-7- O -β- d -glucopyranosyl (1 → 3)- O -β- d -glucopyranoside ( 1 ), tectorigenin-7- O -β- d -deoxyallopyranoside ( 2 ), and tectorigenin-7- O -β- d -quinovopyranoside ( 3 ). In addition, all of the compounds were tested for their hepatoprotective activities against APAP-induced HepG2 cell damage and inhibitory activities against aldose reductase. Compounds 2 , 10 and 11 (10 μM) showed a certain degree of inhibitory activity against aldose reductase, and compounds 1 , 4 and 9 (10 μM) exhibited pronounced hepatoprotective activities against APAP-induced HepG2 cell damage in vitro. [ABSTRACT FROM AUTHOR]

Two new lupane saponins, Schekwanglupasides A and B ( 1 and 2 ), together with three esters ( 3 – 5 ) of known lupane saponins were isolated from the aerial parts of Schefflera kwangsiensis . The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 2 and 4 (10 μM) exhibited moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage. [ABSTRACT FROM AUTHOR]

Four new triterpenoid saponins, schekwangsiensides H–K ( 1 – 4 ) were isolated from the aerial parts of Schefflera kwangsiensis , together with fifteen esters ( 5 – 19 ) of known saponins. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 3 , 8 , 17 , and 18 exhibited weak inhibitory activities against fructose-1,6-bisphosphatase (FBPase1). [ABSTRACT FROM AUTHOR]

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]

Phytochemical investigation of the aerial parts of Lysimachia clethroides led to the isolation of a new acylated flavonol glycoside ( 1 ) and a new δ-truxinate derivative ( 2 ), together with three known acylated flavonol glycosides. The structures of the new compounds were determined by spectroscopic methods and chemical evidence as quercetin-3- O -β- d -(6- O-Z - p -coumaroyl)glucopyranoside ( 1 ) and monomethyl 3,3′,4,4′-tetrahydroxy-δ-truxinate ( 2 ), respectively. All of the isolates were evaluated for their in vitro inhibitory activity against aldose reductase. [ABSTRACT FROM AUTHOR]

Eleven new oleanane-type triterpenoid saponins were isolated from the aerial parts of Schefflera kwangsiensis ( 1 – 11 ), together with nine esters ( 12 – 20 ) of known saponins. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 2 , 3 , 5 , 7 , 8 , 11 – 13 , 15 , 17 and 18 (10 μM) exhibited moderate hepatoprotective activity against d -galactosamine-induced HL-7702 cell damage. [ABSTRACT FROM AUTHOR]

Abstract: Two new eudesmane-type sesquiterpene lactones, 1-one-4-epi-alantolactone (1) and 4α,13-dihydroxy-5,7(11)-eudesmadien-12,8-olide (2), were isolated from the roots of Inula racemosa, together with six known compounds (3–8). The cytotoxic activities against five human cancer cell lines had been tested and compounds 3, 6, 7 and 8 exhibited moderate cytotoxic activities. Compounds 4 and 8 showed potent in vitro activities against the release of β-glucuronidase in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF), with the inhibitory ratios 65.4% (P <0.01) and 80.5% (P <0.001), at concentration of 10μM, respectively. [Copyright &y& Elsevier]

Abstract: From the stem bark of Morus wittiorum, one new Diels–Alder type adduct wittiorumin G (1) and three new 2-arylbenzofuran derivatives wittifurans P–R (2–4) along with five known Diels–Alder type adducts albafuran C, sorocein A, mulberrofuran E, mulberrofuran F and mulberrofuran O were isolated. Their structures were determined on the basis of spectroscopic analysis. Compounds 2–4 and two known compounds sorocein A and mulberrofuran F were evaluated for their antioxidant activity in a Fe2+/cysteine-induced microsomal lipid peroxidation assay and cytotoxicity against five human cancer cell lines respectively. [Copyright &y& Elsevier]

Phytochemical investigation of the ethanol extract of rhizomes of Iris tectorum resulted in the isolation and characterization of two new flavonoid glycosides, tectorigenin-7- O -β- d -fucopyranoside ( 1 ), 3,5,4′-trihydroxy-7,3′-dimethoxyflavanone-5- O -α- l -rhamnopyranoside ( 2 ), together with two known ones ( 3 , 4 ). The rhamnose substituent at C-5 displayed uncommon connection in naturally occurring flavonoid glycosides. Their structures were elucidated on the basis of extensive spectroscopic analysis. All of the isolates were evaluated for their in vitro inhibitory activity against aldose reductase. [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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Abstract: Three 6H-dibenzo[b,d]pyran-6-one glycosides named lysilactones A–C (1–3) were isolated from the aerial parts of Lysimachia clethroides. Their structures were elucidated using spectroscopic analysis and chemical evidence. This is the first report of 6H-dibenzo[b,d]pyran-6-one glycosides. Furthermore, we have finished a total synthesis of lysilactone A. The key step is a Suzuki coupling used for the construction of the central biaryl bond. Lysilactone A was prepared in eight steps starting from phloroglucinic acid and orcinol, where the longest linear sequence is seven steps. [Copyright &y& Elsevier]

Abstract: Nine new diterpenes, named jiadifenoic acids A–I (1–9), together with 10 known analogues were isolated from the roots of Illicium jiadifengpi. Their structures were elucidated by extensive spectroscopic analysis and circular dichroism (CD) experiments. Jiadifenoic acid A (1) is a novel dimeric diterpene with a rare spiro[bicyclo[2.2.2]-oct-5-ene-2,1′-cyclopentan]-3-one motif. A plausible biosynthetic pathway of compound 1 was also postulated. All isolated compounds were evaluated in vitro for their antiviral activities against Coxsackie virus B2, B3, B4, and B6. Among them, 2, 3, and 15 were the most potent inhibitors. Structure–activity relationship (SAR) was also discussed in this paper. [Copyright &y& Elsevier]

Abstract: Three new water-soluble alkaloids (1–3) together with twelve known compounds (4–15) have been isolated from the water extract of leaves of Suregada glomerulata. Their structures were determined by spectroscopic analysis and chemical method. Compounds 1–3 were evaluated for their in vitro inhibitory activity against α-glucosidase and HIV-1 replication. However, no significant activities were found. [Copyright &y& Elsevier]

Investigation of an ethanol extract from the stem bark of Morus wittiorum led to the isolation of five new 2-arylbenzofuran derivatives that were named wittifuran S, wittifuran T, wittifuran V, wittifuran W and wittifuran X (1 – 5). Structures were determined on the basis of spectroscopic analysis. Two new wittifurans and five previously isolated compounds were assayed for antioxidant and anti-inflammatory activity. [Copyright &y& Elsevier]

Abstract: A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H1 antihistamine activity. For the evaluation of H1 antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7, 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with γ-alkylidene butenolide. Their H1 antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7, 8a and 8g display potent activity inhibiting histamine-induced effects. [Copyright &y& Elsevier]

Processive phytochemistry and pharmacological investigation of Schefflera leucantha R.Vig. (Araliaceae) led to the isolation of fifteen known compounds: a nucleobase (1), six small aromatic molecules (2 – 7), three phenylpropanoids (8–10), four lignans (11 – 14) and a fatty acid derivative (15). Spectroscopic methods were used to establish the structure and configuration of isolates, followed by their unambiguous confirmation with literature data. We report for the first time (to the best of our knowledge), the isolation of β -amino-3-methoxy-4-hydroxybenzene-ethanol (4) from a natural source. Furthermore, compounds 1 , 5 , 9 – 15 are being reported from Araliaceae family for the first time, whereas compounds 2 , 3 , 6 – 8 from the genus Schefflera for the first time. The biological screening results show that compounds 9 and 10 induce a moderate inhibitory effect on aldose reductase, while compounds 3 , 5 , and 8 display significantly high neuroprotective activities. • Fifteen known compounds were isolated from Schefflera leucantha R.Vig. • Compound 4 was isolated from a natural source for the first time. • Compound 1 , 5 , 9 – 15 are being reported from Araliaceae family for the first time. • Compound 2 , 3 , 6 – 8 are being reported from the genus Schefflera for the first time. [ABSTRACT FROM AUTHOR]

Three new iridal-type triterpenoids (1– 3) featuring a rearranged homofarnesylside chain were isolated from the rhizomes of Iris tectorum. Compounds 2 and 3 were found to be a pair of epimers. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. A possible biosynthetic pathway for them was postulated. Moreover, the mixture of compounds 2 and 3 exhibited moderate neuroprotective activity against serum deprivation-induced PC12 cell death. Unlabelled Image [ABSTRACT FROM AUTHOR]