Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation

Abstract

Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC₅₀ 0.30 to 1.01 mg mL^?1. Compound 3 exhibited activity against HepG-2 cell lines with IC₅₀ 8.99?μM. Compound 7 exhibited activity against Hela cell lines with IC₅₀ 2.53?μM and BGC-823 cell lines with IC₅₀ 7.77?μM. Moreover, compound 7 showed antioxidant with IC₅₀ 12?µM compared to the positive control with IC₅₀ 77?µM. Compound 16 exhibited activity against HepG-2 cell lines with IC₅₀ 1.05?μM and MCF-7 cell lines with IC₅₀ 1.89?μM. These results indicated that this plant might be potential in natural medicine and healthy food.     

Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent antibreast cancer agents

Herein, we report the synthesis of fluorescent 1,4-dihydropyridine-linked bis-triazoles (2a–2n) through Hantzsch synthesis by the condensation of o/m-chloro-substituted benzaldehyde, ethyl 3-oxo-4(prop-2-yn-1-yloxy)butanoate, and ammonium acetate in the presence of Ba(NO₃)₂ as a catalyst followed by the click reaction of resultant Hantzsch product (1) with various aromatic as well as aliphatic azides. All the synthesized compounds were well characterized by ¹H-NMR, ¹³C-NMR, FTIR, and HRMS spectral techniques. Antibreast cancer evaluation of all the synthesized derivatives revealed that the compounds 2f (IC₅₀?=?7?±?0.02?µM) and 2g (IC₅₀?=?5?±?0.03?µM) showed better anticancer activity (lower IC₅₀) than the standard drug tamoxifen (IC₅₀?=?11.2?±?0.01?µM) against breast carcinoma (MDA-MB-231) cell line. The synthesized compounds were also screened against normal human embryonic kidney (HEK-293) cell line and found to be nontoxic. The fluorescent nature and cytotoxicity assay of these newly synthesized hybrids recommend their utility in tumor cell imaging.     

Synthesis of spirooxindoles promoted by the deep eutectic solvent,ZnCl2+urea via the pseudo four-component reaction: anticancer,antioxidant, and molecular docking studies

Abstract

Various spirooxindoles (7a–c, 8a–c, 9a–c, and 10a–c) were efficiently synthesized using deep eutectic solvent ZnCl₂+urea and well characterized using IR, ¹H NMR, and ¹³C NMR spectroscopic techniques. The biological screening results showed that the compound 9a exhibited potent anticancer activity against MCF7 and HeLa cell lines with IC₅₀ values 6.47?±?0.01 and 9.14?±?0.32?µM, respectively. The compound 7c exhibited potent activity against the HeLa cell line with IC₅₀ value 6.81?±?0.01?µM. The compound 9a exhibited a potent antioxidant activity with IC₅₀ value 7.34?±?0.17?µM. The comparative molecular docking study against the cancer proteins EGFR and HER2 revealed that the EGFR was the best target protein receptor for the target compounds. Among all the compounds, the compound 9a exhibited the least binding energy ?10.72?kcal/mol against the protein EGFR (PDB ID: 4HJO).     

Perisomalien A,a new cytotoxic scalarane sesterterpene from the fruits of Periploca somaliensis

Abstract

The CHCl₃ fraction of MeOH extract of Periploca somaliensis (family Asclepiadaceae) fruits afforded a new scalarane sesterterpene, namely perisomalien A (1), along with lupeol acetate (2), β-amyrin (3), cycloart-23Z-ene-3β,25-diol (4), and β-sitosterol-3-O-β-D-glucopyranoside (5). Their chemical structures were established by various spectroscopic analyses, in addition to comparison with the formerly reported data. Moreover, the cytotoxic activity of these metabolites was assessed towards MCF-7, HepG2, and HCT-116 tumour cell lines using sulforhodamine B (SRB) assay. Compound 4 showed the most potent cytotoxic profile with IC₅₀ 9.0?µM towards MCF-7, compared to doxorubicin (IC₅₀ 0.18?µM). Also, 1 and 4 possessed the most potent effect towards HepG2 with IC₅₀s 26.7 and 25.9?μM, respectively. In addition, all tested compounds showed cytotoxic effects with IC₅₀ values ranging from 19.9 to 39.3?µM against HCT-116.     

Chemical constituents and cytotoxic activity from the wood-decaying fungus Xylaria sp. SWUF08-37

Abstract

A new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3–15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey’s method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC₅₀?=?19.60?µg/mL), HT29 (IC₅₀?=?17.31?µg/mL), HCT116 (IC₅₀?=?14.28?µg/mL), MCF-7 (IC₅₀?=?15.38?µg/mL), and Vero (IC₅₀?=?24.97?µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines.     

HPLC-DAD-SPE-NMR isolation of tetracyclic spiro-alkaloids with antiplasmodial activity from the seeds of Erythrina latissima

Abstract

Seven tetracyclic spiro-alkaloids, i.e. glucoerysodine (1), erysodine (2), epi-erythratidine (3), erysovine (4), erythratidine (5), erysotrine (6) and erythraline (7) were isolated from the seeds of Erythrina latissima by means of conventional separation methods and HPLC-DAD-SPE-NMR. Their structures were elucidated by spectroscopic means. This is the first report on the isolation of compounds 3, 5 and 6 from this plant. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) was assessed in vitro. Erysodine (2) and erysovine (4) showed moderate activity (IC₅₀ 6.53?µM and 4.05?µM, respectively), compared with the standard chloroquine (IC₅₀ = 0.14?µM). No cytotoxicity was observed in a concentration up to 64.0?µM.     

Rotenoid and isoflavone metabolites from an antioxidant seed extract of Dalbergia lanceolaria subsp. paniculata (roxb.) thoth

Abstract

A new rotenoid named 12-O-methylrotenolol along with five known rotenoid and isoflavone metabolites were isolated from the seeds of Dalbergia lanceolaria subsp. paniculata, collected from Egypt. The structures of these compounds were identified by physical and spectroscopic data measurements ([α]_D, UV, 1D- and 2D-NMR and MS). The methanol extract of the seeds exhibited strong antioxidant activity with IC₅₀ value 0.7?µg/µl against DPPH radical, in respect to quercetin as antioxidant reference (IC₅₀ 1.5?μM), while the tested compounds from this extract showed weak activities with IC₅₀ values ranged from 19.6 to 33.0?µM.     

A new depsidone derivative from mangrove sediment derived fungus Lasiodiplodia theobromae

A new depsidone derivative botryorhodine I (1), along with eight known compounds (2-9) were obtained from solid rice cultures of the fungal strain, Lasiodiplodia theobromae M4.2-2 isolated from a mangrove sediment sample. The structures of the isolated compounds were elucidated on the basis of 1?D and 2?D NMR analysis as well as by HRESIMS. All compounds were evaluated for their cytotoxic potential against the mouse lymphoma cell line L5178Y as well as for their antibacterial activities against a panel of Gram-positive and Gram-negative bacterial strains. Compound 3 revealed potent cytotoxic activity with an IC₅₀ of 7.3?µM whereas compound 7 showed selective anti-bacterial activity against different S. aureus and E. faecium bacterial strains with MIC value of 25?µg/ml.     

Bioactive xanthoquinodins and epipolythiodioxopiperazines from Chaetomium globosum 7s-1, an endophytic fungus isolated from Rhapis cochinchinensis (Lour.) Mart

Abstract

A new xanthoquinodin B9 (1), together with two known xanthoquinodins, xanthoquinodin A1 (2) and xanthoquinodin A3 (3), three epipolythiodioxopiperazines, chetomin (4), chaetocochin C (5) and dethio-tetra(methylthio)chetomin (6), and four other compounds, chrysophanol (7), emodin (8), alatinone (9), and ergosterol (10) were isolated from the endophytic fungus Chaetomium globosum 7s-1, isolated from Rhapis cochinchinensis (Lour.) Mart. All isolated structures were established based on their spectroscopic data analyses. Compounds 1–6 showed antibacterial activity against Gram positive bacteria with MICs ranging from 0.02?pM to 10.81 µM. Compounds 1–6 also exhibited cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines (IC₅₀ 0.04–18.40 µM). However, they were cytotoxic towards a normal cell line (Vero cell) with IC₅₀ values ranging from 0.04 to 3.86 µM.     

1,2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity

Abstract

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a–d and 11a–e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25–200?µM concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a–d and 11a–e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a–d without glycine spacer have shown good anticancer activity compared to compounds 11a–e with glycine spacer. Compound 9b has shown moderate activity with IC₅₀ values 4.72?±?0.72 and 4.39?±?0.809?µM against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC₅₀ 2.36?±?0.34?µM against MCF7 cell line as compared to fluorouracil with IC₅₀ 45.04?±?1.02?µM.     

Synthesis and anticancer activities of proline-containing cyclic peptides and their linear analogs and congeners

A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2?h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC₅₀ of 2.73 and 4.3?µM, respectively compared to their Boc-protected analogs 2a (IC₅₀ 20?µM) and 3c (IC₅₀ 38.51?µM) and cyclic peptides 2 (>100?µM) and 3 (47?µM). These results were further validated by biological experiments such as colony formation and wound healing assays.     

Anti-glycating and anti-oxidant compounds from traditionally used anti-diabetic plant Geigeria alata(DC) Oliv. & Hiern.

Abstract

A new sesquiterpene lactone geigerianoloide (1) and four known flavonoids axillarin (2), quercetin (3), 3-methoxy-5,7,3',4'-tetrahydroxy-flavone (4) and hispidulin (5) were isolated from Geigeria alata (DC) Oliv. & Hiern. (Asteraceae). Structures were deduced using ¹H- and ¹³C- NMR spectroscopy, mass spectrometry, while the structure of compound 1 was also deduced using X-ray crystallography technique.

Geigeria alata is traditionally used for diabetes, therefore compounds were tested for anti-glycation activity, in which compounds 2 and 3 showed potent activities (IC₅₀ values of 246.97?±?0.83 and 262.37?±?0.22 µM, respectively) compared to IC₅₀ value 294.50?±?1.5 µM of rutin. Moreover, compound 4 exhibited a comparable activity to rutin (IC₅₀?=?293.28?±?1.34 µM). Compound 5 showed a weak activity.

Compounds 2, 3, and 4 exhibited potent DPPH radical scavenging activity (IC₅₀?=?0.1?±?0.00, 0.13?±?0.00 and 0.15?±?0.01 µM, respectively). Compounds 2, 3, and 4 demonstrated significant superoxide anion scavenging activity with IC₅₀ values of 0.14?±?0.001, 0.17?±?0.00, and 0.11?±?0.006 µM, respectively.     

Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents

Abstract

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13?g (IC₅₀ = 0.514?μM) and 13o (IC₅₀ = 0.275?μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC₅₀ = 0.511?μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs.     

Calaxanthones A-C,three new xanthones from the roots of Calophyllum calaba and the cytotoxicity

Three new xanthones, named calaxanthones A-C (1–3), along with 17 known xanthones (4–20) were isolated from the roots of Calophyllum calaba. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell lines with IC₅₀ values in the range of 0.82–5.04 μM. Furthermore, compound 6 showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC₅₀ values of 7.06, 5.27 and 9.64 μM, respectively. Additionally, compound 7 showed potent cytotoxicity against KB cell with an IC₅₀ value of 4.62 μM.     

New cytotoxic bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch

Abstract

Three new bufadienolides 14β, 16β-dihydroxy-3β-[β-D-glucopyranosyl-(1→6)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (1), 14β-hydroxy-3β-[β-D-glucopyranosyl-(1→4)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (2) and hellebrigenin-3-O-β-D-glucosyl-(1→4)-β-D-glucoside (3), together with eight known bufadienolides (4–11) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by extensive spectroscopic methods and acid hydrolysis. Compounds 1–7 were evaluated for their cytotoxic activity against HCT116, A549 and HepG2 tumor cell lines. Compound 1 exhibited moderate cytotoxicity against HepG2 cells with IC₅₀ value of 15.1?±?1.72?μM. Compounds 5 and 6 exhibited moderate cytotoxicity against HCT116 cells with IC₅₀ values of 15.12?±?0.58?μM and 13.17?±?2.34?μM, respectively.     

Design,synthesis, in vitro and in silico studies of naproxen derivatives as dual lipoxygenase and α-glucosidase inhibitors

A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC₅₀ 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC₅₀ 36.53 ± 0.51 µM) and 4d (IC₅₀ 49.62 ± 0.12 µM) against standard drug baicalein (IC₅₀ 22.46 ± 1.32 µM) and quercetin (IC₅₀ 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC₅₀ 1.13 ± 0.62 µM ?123.47 ± 0.37 µM. Among these compounds, 4e (IC₅₀ 1.13 ± 0.62 µM), 5b (IC₅₀ 1.19 ± 0.43 µM), 8c (IC₅₀ 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC₅₀ 4.86 ± 0.14 µM), and baicalein (IC₅₀ 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC₅₀ 1.0 ± 1.13 µM ? 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC₅₀ 375.82 ± 1.76 µM), while compound 6c (IC₅₀ 1.0 ± 1.13 µM) and 7c (IC₅₀ 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.     

Neoclerodane diterpenoids from Scutellaria barbata with cytotoxic activities

Abstract

Two new neoclerodane diterpenoids, barbatin F (1), barbatin G (2) together with four known compounds, scutebata A (3), scutebata B (4), scutebata C (5) and scutebata P (6) were isolated from the whole plant of Scutellaria barbata D.Don. Their structures were elucidated on the basis of spectroscopic studies. In vitro cytotoxicity of selected compounds against cancer cell lines LoVo, SMMC-7721, HCT-116, and MCF-7 were evaluated, compound 1 and 2 showed weak cytotoxic activities against HCT-116 colon cancer cell lines with IC₅₀ value of 44.3, 32.3?μM, respectively, while compound 3 and 4 exhibited moderate cytotoxic activities against four tested human cancer cell lines with IC₅₀ values of 5.31～28.5?μM.     

The new ether derivative of phenylpropanoid and bioactivity was investigated from the leaves of Piper betle L.

Abstract

A new ether derivative of phenylpropanoid compound, γ-(γ′-isohydroxychavicol)-chavicol octanyl ether (K1) along with one known phenylpropanoid named allyl-pyrocatechol or hydroxychavicol (2) were isolated from Piper betle var. kali collected from Tumluk district, West Bengal India. We first report the presence of compound K1 in the genus Piper. Their structures were established on the basis of various spectroscopic analyses. Compounds K1 and 2 showed excellent antioxidant DPPH free radical scavenging activity with IC₅₀ values of 4.61 and 4.12?µg/mL compared to ascorbic acid as a standard antioxidant drug with IC₅₀ value of 3.42?µg/mL, respectively. Evaluation of in vitro cytotoxic activities of compounds K1 and 2 showed significant effects against human oral cancer cell lines (AW13516 and AW8507), human hepatoma cell lines (HEPG2 and PLC-PRF-5) and a human pancreatic cell line (MIA-PA-CA-2), compared to Doxorubicin^® as a standard cytotoxic drug with GI₅₀ values of <10 and 18.18?µg/mL.     

Two new bioactive triterpenoids from the roots of Colubrina asiatica

Abstract

Two new ceanothane triterpenes, 3,7-O,O-dibenzoyl ceanothic acid methylester (1) and 3-O-acetyl-7-O-benzoyl ceanothic acid methylester (2), along with nine known compounds (3–11), were isolated from the roots of Colubrina asiatica. The isolated compounds were identified by spectroscopic evidence. Compounds 1 and 2 showed antimalarial activity against Plasmodium falciparum with IC₅₀ values of 4.67 and 3.07?µg/mL, respectively. Compound 2 also showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 6.25?µg/mL). In addition, compounds 1, 2, 10 and 11 showed cytotoxicity against three cancer cell lines (KB, NCI-H187 and MCF-7) with IC₅₀ values ranging from 8.32 to 46.72?µg/mL.     

Chemical investigation of Cannabis sativa leading to the discovery of a prenylspirodinone with anti-microbial potential

The discovery of a new spiran based natural product, prenylspirodinone (1), together with six known cannabinoids (2–7) from the leaves of Cannabis sativa (Marijuana) is reported. All compounds were screened for antifungal and antibacterial activity against a panel of microbial pathogens and exhibited antimicrobial activities with IC₅₀ values ranging from 2.6 to 49.6?µM. Compound 2, a propyl substituted cannabidiol, was determined to be a specific inhibitor against C. albicans (IC₅₀ 11.9?µM) and can be considered as a new lead against Candidiasis.