Two New Cytotoxic Maytansinoids Targeting Tubulin from Trewia nudiflora

Planta Medica ◽  
2021 ◽  
Author(s):  
Chun Lei ◽  
Ya-Nan Li ◽  
Jia-Nan Li ◽  
Yu-Bo Zhou ◽  
Ming-Jun Cui ◽  
...  
Keyword(s):  
Human Tumor ◽  
Crystallographic Analysis ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
X Ray ◽  
Trewia Nudiflora ◽  
Ic50 Values ◽  
Mcf 7

AbstractTwo new maytansinoids, N-methyltreflorine (1) and methyltrewiasine (2), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3 – 5). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 and 2 was determined by X-ray crystallographic analysis. Compounds 1 – 5 exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 – 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1 and 4 also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1 and 2 significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.

Reactions of 2-cyano-3-ferrocenylacrylonitrile with malononitrile: formation of 4-ferrocenylpyridine-3,5-dicarbonitrile derivatives and sodium polymeric complexes containing carbanionic ligands

2014 ◽  
Vol 86 (11) ◽  
pp. 1839-1852 ◽  
Author(s):  
Elena Ivanovna Klimova ◽  
Marcos Martínez García ◽  
Jessica Jazmin Sánchez García ◽  
Teresa Ramírez Apan ◽  
Andrei V. Churakov ◽  
...  
Keyword(s):  
Human Tumor ◽  
Tumor Cell Lines ◽  
X Ray Diffraction ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
X Ray ◽  
Biological Specificity ◽  
Polymeric Complexes ◽  
Mcf 7

Abstract The reactions of 2-cyano-3-ferrocenylacrylonitrile with malononitrile in a EtOH/H2O or MeOH/H2O medium in the presence of Na2CO3 afforded 6-alkoxy-2-amino-4-ferrocenylpyridine-3,5-dicarbonitriles 3a,b (multi-component condensation), 6-alkoxy-2-amino-4-ferrocenyl-3-ferrocenylmethyl-3,4-dihydropyridine-3,5-dicarbonitriles 4a,b (multi-component cyclodimerization) and Na+ polymeric complexes: {[Na+(2-ferrocenyl(tetracyano)propenyl)–L]∞5a,b and [Na+(2-amino-3,5-dicyano-4-ferrocenyl-6-pyridyl-dicyanomethyl)–L]∞6a,b, where L = ethanol, methanol. Complexes with L = acetonitrile, dimethylformamide, acetone, ethyl acetate were prepared by recrystallization. The structures of the compounds 3b, 4b and Na+ polymeric complexes were established by the spectroscopic data and X-ray diffraction analysis. Two compounds 3a and 4a were tested in vitro against six human tumor cell lines U-251, PC-3, K-562, HCT-15, MCF-7 and SKLU-1 to assess their in vitro antitumor activity. The results suggest biological specificity towards PC-3, K-562 and HCT-15 cells for compound 3a, and towards PC-3 cell for compound 4a at doses of 50 μM, which are lower than cis-platin.

scholarly journals Bioactivities of essential oils from different parts of Spiranthera odoratissima (Rutaceae)

Rodriguésia ◽  
2020 ◽  
Vol 71 ◽  
Author(s):  
Fernando Duarte Cabral ◽  
Cassia Cristina Fernandes ◽  
Arthur Barcelos Ribeiro ◽  
Iara Squarisi Squarisi ◽  
Denise Crispim Tavares ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Normal Cell ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Mcf 7

Abstract This paper aims to investigate, for the first time, in vitro antitubercular, antileishmanial and antiproliferative activities of essential oils (EOs) from S. odoratissima leaves and flowers - grown in midwestern Brazil - against Mycobacterium tuberculosis, promastigote forms of Leishmania amazonensis and human tumor cell lines. Antimycobacterial activity of EOs was evaluated in terms of the minimal inhibitory concentration (MIC). EOs from leaves and flowers showed to be active antimicrobials against M. tuberculosis, since MIC values were 150 µg/mL and 162.5 µg/mL, respectively. Both EOs exhibited significant activity against promastigote forms of L. amazonensis; IC50 values (50% growth inhibition) were 14.36 ± 2.02 (EOs from leaves) and 19.89 ± 2.66 µg/mL (EOs from flowers). Antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor (MCF-7, HeLa and M059J) cell lines was performed by the XTT assay; results were expressed as IC50 (50% cell growth inhibition) and the selective index was calculated. IC50 values of EOs from leaves and flowers obtained in normal cell lines for were 502.97 ± 40.33 µg/mL and 370.60 ± 2.01 µg/mL, respectively. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were significantly lower than those obtained in normal cell lines of MCF-7 cells (367.57 ± 4.46 µg/mL-EOs from leaves and 357.70 ± 1.85 µg/mL-EOs from flowers) and M059J cells (492.53 ± 56.67 µg/mL-EOs from leaves and 324.90 ± 6.72 µg/mL-EOs from flowers), thus, indicating selectivity. These in vitro results showed that EOs from S. odoratissima may be an antimycobacterial, antiparasitic and antitumor agent.

scholarly journals In Vitro Antitumor Activity of Endophytic Fungi Isolated From the Mexican Cactus Pachycereus Marginatus (DC.) Britton & Ros

2021 ◽  
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Endophytic Fungi ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Normal Cells ◽  
Human Tumor Cell Lines ◽  
Ht 29 ◽  
Mcf 7

Abstract Background: Arid zone plants such as cacti are known to harbor diverse groups of endophytic fungi, which represent potential sources of new compounds with anticancer properties. In the present study we isolated, identified, and characterized Pachycereus marginatus (DC.) Britton & Ros endophytic fungi with cytotoxic activity against murine and human tumor cell lines.Methods: Endophytic fungi were isolated from P. marginatus stems. Methanol extracts were then obtained from fungi liquid cultures and their cytotoxic activity at concentrations ranging from 31 µg/ml to 250 µg/ml against murine L5178Y-R lymphoma, human colorectal adenocarcinoma HT-29, and human breast cancer MCF-7 was evaluated by the colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay, using the normal cells Macacus rhesus monkey epitelial kidney MA-104 and human peripheral blood mononuclear cells (PBMC) as controls. IC50 values were obtained and the selectivity index (SI) was calculated from the IC50 ratio of cancer cells and normal cells. Furthermore, molecular identification of fungi showing cytotoxic activity was determined by the internal transcribed spacer molecular marker.Results: The Cladosporium sp. PME-H008 strain showed significant (P < 0.01) 94.3% and 36.8% cytotoxicity against L5178Y-R and HT-29 cells, respectively. The highest SI was observed by L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMC respectively. In addition, the Metarhizium anisopliae PME-H007 strain was more effective against MCF-7 with 55.8% cytotoxicity. The lowest IC50 was obtained with the Aspergillus sp. PME-H005 strain at 95.21 µg/ml against the MCF-7 cell line, followed by PME-H008 strain at 101 µg/ml against L5178Y-R cells.Conclusion: P. marginatus endophytic fungi showed in vitro cytotoxic activity against murine and human tumor cell lines, without affecting normal cells.

scholarly journals Five New Meroterpenoids from the Fruiting Bodies of the Basidiomycete Clitocybe clavipes with Cytotoxic Activity

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4015 ◽  
Author(s):  
Zhaocui ◽  
Xudong ◽  
Hanqiao ◽  
Xinyi ◽  
Guoxu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Fruiting Bodies ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Ic50 Values

Five new meroterpenoids, clavipols A–B (1–2) with a 12-membered ether ring and clavilactones G–I (3–5) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the basidiomycete Clitocybe clavipes. Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds (1–5) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound 4 exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC50 values of 23.5 and 14.5 µM, respectively.

scholarly journals New Cytotoxic Cycloartane Triterpenes from the Aerial Parts of Actaea heracleifolia (syn. Cimicifuga heracleifolia)

Planta Medica ◽  
2018 ◽  
Vol 85 (02) ◽  
pp. 154-159
Author(s):  
Qiang-Qiang Shi ◽  
Wei-Hua Wang ◽  
Jing Lu ◽  
Da-Shan Li ◽  
Lin Zhou ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Tumor ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Chemical Structures ◽  
Aerial Parts ◽  
Ic50 Values ◽  
Weak Activity ◽  
Mcf 7

AbstractOne new 15,16-seco-cycloartane triterpene (1), three new cycloartane triterpene glycosides (2–4), and five known compounds (5–9) were isolated from the aerial parts of Actaea heracleifolia. The chemical structures of these compounds were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other spectroscopic methods. Selected compounds were evaluated for their cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in vitro. Compounds 3 and 4 showed weak activity against the HL-60, A-549, and MCF-7 cell lines with IC50 values ranging from 21.34 to 36.98 µM.

scholarly journals Cytotoxic and Antileishmanial Components from the Bark Extract of Ruyschia phylladenia from Monteverde, Costa Rica

2017 ◽  
Vol 12 (1) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Kelly Marie Steinberg ◽  
Samon Shrestha ◽  
Noura S. Dosoky ◽  
Lianet Monzote ◽  
Abel Piñón ◽  
...  
Keyword(s):  
Costa Rica ◽  
Betulinic Acid ◽  
Human Tumor ◽  
Bark Extract ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Isolation And Identification ◽  
Human Tumor Cell Lines ◽  
Mcf 7

The bark of Ruyschia phylladenia was collected from Monteverde, Costa Rica, and extracted with acetone. Bioactivity-directed chromatographic separation of the crude acetone bark extract of R. phylladenia led to isolation and identification of lupeol, betulinic acid, and isofraxidin. Lupeol and betulinic acid showed in-vitro cytotoxic activity to MCF-7, MDA-MB-231, and 5637 human tumor cell lines. Isofraxidin was not cytotoxic, but did show antileishmanial activity to Leishmania amazonensis promastigotes.

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

scholarly journals Setosphlides A–D, New Isocoumarin Derivatives from the Entomogenous Fungus Setosphaeria rostrate LGWB-10

2021 ◽  
Author(s):  
Wenbin Gao ◽  
Xiaoxia Wang ◽  
Fengli Chen ◽  
Chunqing Li ◽  
Fei Cao ◽  
...  
Keyword(s):  
Harmonia Axyridis ◽  
Chemical Shifts ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Entomogenous Fungus ◽  
Planar Structures ◽  
Mcf 7 ◽  
C Nmr

Abstract Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives, setosphlides A–D (1–4), and four known analogues (5–8). Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods. The absolute configurations of isocoumarin nucleus for 1–4 were elucidated by their ECD spectra. The C-10 relative configurations for the pair of C-10 epimers (1 and 2) were established by comparing the magnitude of the computed 13C NMR chemical shifts (Δδcalcd.) with the experimental 13C NMR values (Δδexp.) for the epimers. All of the isolated compounds (1–8) were evaluated for their cytotoxicities against four human tumor cell lines MCF-7, MGC-803, HeLa, and Huh-7. Graphic Abstract

scholarly journals Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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