scholarly journals Synthesis and antiproliferative activity of some A- and B modified D-homo lactone androstane derivatives

2013 ◽  
pp. 289-300
Author(s):  
Marina Savic ◽  
Katarina Penov-Gasi ◽  
Marija Sakac ◽  
Dimitar Jakimov ◽  
Evgenija Djurendic
Keyword(s):  
Antiproliferative Activity ◽  
Malignant Cell ◽  
Chromium Vi ◽  
Oppenauer Oxidation ◽  
Hydrolysis Of ◽  
Androstane Derivatives ◽  
Ht 29 ◽  
Unstable Intermediate ◽  
Mcf 7

An efficient synthesis of several A- and B-modified D-homo lactone androstane derivatives from 3?-hydroxy-17-oxa-D-homoandrost-5-en-16-one (1) is reported. 17-Oxa-Dhomoandrost- 4-ene-3,16-dione (2), obtained by the Oppenauer oxidation of compound 1, was converted via the unstable intermediate 3,16-dioxo-4,17-dioxa-D-homoandrostane- 5?-carboxaldehyde (3) to 17-oxa-D-homo-3,5-seco-4-norandrostan-5-one-3-carboxylic acid (4), which was also obtained directly from compound 2. Compound 1 was acetylated to give 17-oxa-D-homoandrost-5-en-16-on-3?-yl acetate (5) which was then oxidized with chromium(VI)-oxide in 50% acetic acid or with meta-chlorperbenzoic acid and chromium(VI)-oxide to yield compounds 6-8 and 5?-hydroxy-17-oxa-D-homoandrostane- 6,16-dion-3?-yl acetate (9), respectively. The oximination of compound 9 gave a mixture of 6(E)-hydroximino-5?-hydroxy-17-oxa-D-homoandrostan-16-on-3?-yl acetate (10) and 6(Z)-hydroximino-5?-hydroxy-17-oxa-D-homoandrostan-16-on-3?-yl acetate (11), the hydrolysis of which gave 6(E)-hydroximino-3?,5?-dihydroxy-17-oxa-D-homoandrostan- 16-one (12) and 6(Z)-hydroximino-3?,5?-dihydroxy-17-oxa-D-homoandrostan-16-one (13). 6-Nitrile-17-oxa-5,6-seco-D-homoandrostane-5,16-dion-3?-yl acetate (14) was obtained under the Beckmann fragmentation of compounds 10 and 11. Only pure and stable compounds (1, 2, 4, 5, 9 and 14) were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562) and one non-tumor MRC-5 cell line. Significant antiproliferative activity against MDA-MB-231 cells showed compounds 1, 5 and 9, while compound 2 exhibited a strong antiproliferative activity. Only compound 14 showed weak antiproliferative activity against MCF-7 cells. All tested compounds were not toxic on MRC-5 cells, whereas Doxorubicin was highly toxic on these cells.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

2020 ◽  
Vol 20 ◽  
Author(s):  
Ya-Nan Li ◽  
Ni Ning ◽  
Lei Song ◽  
Yun Geng ◽  
Jun-Ting Fan ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtt Method ◽  
Anthriscus Sylvestris ◽  
Anti Tumor Activity ◽  
Derivatives Of ◽  
Toxicity In Vitro ◽  
Ht 29 ◽  
Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

scholarly journals Synthesis, Structure and In Vitro Anticancer Activity of Pd(II) Complex of Pyrazolyl-s-Triazine Ligand; A New Example of Metal-Mediated Hydrolysis of s-Triazine Pincer Ligand

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 119
Author(s):  
Jamal Lasri ◽  
Matti Haukka ◽  
Hessa H. Al-Rasheed ◽  
Nael Abutaha ◽  
Ayman El-Faham ◽  
...  
Keyword(s):  
Thermal Conditions ◽  
Molar Ratio ◽  
Chloride Salt ◽  
Pincer Ligand ◽  
Hydrogen Bonding Interactions ◽  
Square Planar ◽  
Hirshfeld Analysis ◽  
Hydrolysis Of ◽  
Mcf 7

The square planar complex [Pd(PT)Cl(H2O)]*H2O (HPT: 6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4(1H,3H)-dione) was obtained by the reaction of 2-methoxy-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine (MBPT) pincer ligand with PdCl2 in a molar ratio (1:1) under thermal conditions and using acetone as a solvent. The reaction proceeded via C-N cleavage of one C-N moiety that connects the pyrazole and s-triazine combined with the hydrolysis of the O-CH3 group. The reaction of the chloride salt of its higher congener (PtCl2) gave [Pt(3,5-dimethyl-1H-pyrazole)2Cl2]. The crystal structure of [Pd(PT)Cl(H2O)]*H2O complex is stabilized by inter- and intra-molecular hydrogen bonding interactions. Hirshfeld analysis revealed that the H...H (34.6%), O...H (23.6%), and Cl...H (7.8%) interactions are the major contacts in the crystal. The charges at Pd, H2O, Cl and PT are changed to 0.4995, 0.2216, −0.4294 and −0.2917 instead of +2, 0, −1 and −1, respectively, using the MPW1PW91 method. [Pd(PT)Cl(H2O)]*H2O complex has almost equal activities against MDA-MB-231 and MCF-7 cell lines with IC50 of 38.3 µg/mL.

scholarly journals Model Amphipathic Peptide Coupled with Tacrine to Improve Its Antiproliferative Activity

2020 ◽  
Vol 22 (1) ◽  
pp. 242
Author(s):  
Sara Silva ◽  
Cláudia Alves ◽  
Diana Duarte ◽  
Ana Costa ◽  
Bruno Sarmento ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Drug Repurposing ◽  
Parent Drug ◽  
Ache Inhibitor ◽  
Amphipathic Peptide ◽  
Reference Drug ◽  
Mcf 7

Drug repurposing and drug combination are two strategies that have been widely used to overcome the traditional development of new anticancer drugs. Several FDA-approved drugs for other indications have been tested and have demonstrated beneficial anticancer effects. In this connection, our research group recently reported that Tacrine, used to treat Alzheimer’s Disease, inhibits the growth of breast cancer MCF-7 cells both alone and in combination with a reference drug. In this view, we have now coupled Tacrine with the model amphipathic cell-penetrating peptide (CPP) MAP, to ascertain whether coupling of the CPP might enhance the drug’s antiproliferative properties. To this end, we synthesized MAP through solid-phase peptide synthesis, coupled it with Tacrine, and made a comparative evaluation of the parent drug, peptide, and the conjugate regarding their permeability across the blood-brain barrier (BBB), ability to inhibit acetylcholinesterase (AChE) in vitro, and antiproliferative activity on cancer cells. Both MAP and its Tacrine conjugate were highly toxic to MCF-7 and SH-SY5Y cells. In turn, BBB-permeability studies were inconclusive, and conjugation to the CPP led to a considerable loss of Tacrine function as an AChE inhibitor. Nonetheless, this work reinforces the potential of repurposing Tacrine for cancer and enhances the antiproliferative activity of this drug through its conjugation to a CPP.

scholarly journals Monocyte Infiltration and Differentiation in 3D Multicellular Spheroid Cancer Models

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 969
Author(s):  
Natasha Helleberg Madsen ◽  
Boye Schnack Nielsen ◽  
Son Ly Nhat ◽  
Søren Skov ◽  
Monika Gad ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Multicellular Spheroid ◽  
Tumor Associated Macrophages ◽  
Cancer Models ◽  
Ht 29 ◽  
Mcf 7

Tumor-associated macrophages often correlate with tumor progression, and therapies targeting immune cells in tumors have emerged as promising treatments. To select effective therapies, we established an in vitro 3D multicellular spheroid model including cancer cells, fibroblasts, and monocytes. We analyzed monocyte infiltration and differentiation in spheroids generated from fibroblasts and either of the cancer cell lines MCF-7, HT-29, PANC-1, or MIA PaCa-2. Monocytes rapidly infiltrated spheroids and differentiated into mature macrophages with diverse phenotypes in a cancer cell line-dependent manner. MIA PaCa-2 spheroids polarized infiltrating monocytes to M2-like macrophages with high CD206 and CD14 expression, whereas monocytes polarized by MCF-7 spheroids displayed an M1-like phenotype. Monocytes in HT-29 and PANC-1 primarily obtained an M2-like phenotype but also showed upregulation of M1 markers. Analysis of the secretion of 43 soluble factors demonstrated that the cytokine profile between spheroid cultures differed considerably depending on the cancer cell line. Secretion of most of the cytokines increased upon the addition of monocytes resulting in a more inflammatory and pro-tumorigenic environment. These multicellular spheroids can be used to recapitulate the tumor microenvironment and the phenotype of tumor-associated macrophages in vitro and provide more realistic 3D cancer models allowing the in vitro screening of immunotherapeutic compounds.

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.

Evaluation of Benzamide-chalcone Derivatives as EGFR/CDK2 inhibitor: Synthesis, in-vitro Inhibition, and Molecular Modeling Studies

2021 ◽  
Vol 21 ◽  
Author(s):  
Akshada Joshi ◽  
Heena Bhojwani ◽  
Ojas Wagal ◽  
Khushboo Begwani ◽  
Urmila Joshi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Wild Type ◽  
Chalcone Derivatives ◽  
Ht 29 ◽  
Egfr Kinase ◽  
Mcf 7 ◽  
Mutant Egfr

Background: EGFR (Epidermal Growth Factor Receptor) and CDK2 (Cyclin Dependent Kinase 2) are important targets in the treatment of many solid tumors and different ligands of these receptors share many common structural features. Objective: The study involved synthesis of benzamide-substituted chalcones and determination of their antiproliferative activity as well as preliminary evaluation of EGFR and CDK2 inhibitory potential using both receptor binding and computational methods. Methods: We synthesized 13 benzamide-substituted chalcone derivatives and tested their antiproliferative activity against MCF-7, HT-29 and U373MG cell-lines using Sulforhodamine B Assay. Four compounds were examined for activity against EGFR and CDK2 kinase. The compounds were docked into both EGFR and CDK2 using Glide software. The stability of the interactions for most active compound was evaluated by Molecular Dynamics Simulation using Desmond software. Molecular Docking studies on mutant EGFR (T790M, T790M/L858R, and T790M/C797S) were also carried out. Results: From the SRB assay, we concluded that compounds 1g, and 1k were effective in inhibiting the growth of MCF-7 cell line whereas the other compounds were moderately active. Most compounds were either moderately active or inactive on U373 MG and HT-29 cell line. Compounds 1g and 1k showed good inhibitory activity against CDK2 kinase while 1d and 1f were moderately active. Compounds 1d, 1f, 1g, and 1k were moderately active against EGFR kinase. Molecular docking reveals involvement of one hydrogen bond with Met793 in binding with EGFR however; it was not stable during simulation and these compounds bind to the receptor mainly via hydrophobic contacts. This fact also points towards a different orientation of the inhibitor within the active site of EGFR kinase. Binding mode analysis for CDK2 inhibition studies indicate that hydrogen bonding interaction with Lys 33 and Leu83 are important for the activity. These interactions were found to be stable throughout the simulation. Considering the results for wild-type EGFR inhibition, the docking studies on mutants were performed and which indicate that the compounds bind to the mutant EGFR but the amino acid residues involved are similar to the wild-type EGFR and therefore, the selectivity seems to be limited. Conclusion: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.

scholarly journals Extraction, Chemical Composition, and Anticancer Potential of Origanum onites L. Essential Oil

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2612 ◽  
Author(s):  
Katerina Spyridopoulou ◽  
Eleni Fitsiou ◽  
Eleni Bouloukosta ◽  
Angeliki Tiptiri-Kourpeti ◽  
Manolis Vamvakias ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Essential Oil ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Biological Activities ◽  
Colorectal Cancer Cell Line ◽  
Ht 29 ◽  
Origanum Onites

Origanum species are plants rich in volatile oils that are mainly used for culinary purposes. In recent years, there has been a growing interest in the biological activities of their essential oils. Origanum onites L. is a plant mainly found in Greece, Turkey, and Sicily, whose oil is rich in carvacrol, a highly bioactive phytochemical. The aim of this study was to analyze the chemical composition of Origanum onites essential oil (OOEO), and investigate its potential anticancer effects in vitro and in vivo. GC/MS analysis identified carvacrol as OOEO’s main constituent. In vitro antiproliferative activity was assayed with the sulforhodamine B (SRB) assay against human cancer cell lines from four tumor types. HT-29, a colorectal cancer cell line, was the most sensitive to the antiproliferative activity of OOEO. Wound-healing assay and Annexin V-PI staining were employed to investigate the antimigratory and the pro-apoptotic potential of OOEO, respectively, against human (HT-29) and murine (CT26) colon cancer cells. Notably, OOEO attenuated migration and induced apoptosis-related morphological changes in both cell lines. Prophylactic oral administration of the oil in a BALB/c experimental mouse model inhibited the growth of syngeneic CT26 colon tumors. As far as we know, this is the first report on the antitumor potential of orally administered OOEO.

New binuclear Ni(ii) metallates containing ONS chelators: synthesis, characterisation, DNA binding, DNA cleavage, protein binding, antioxidant activity, antimicrobial and in vitro cytotoxicity

2017 ◽  
Vol 41 (7) ◽  
pp. 2543-2560 ◽  
Author(s):  
G. Kalaiarasi ◽  
Ruchi Jain ◽  
H. Puschman ◽  
S. Poorna Chandrika ◽  
K. Preethi ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Dna Binding ◽  
Protein Binding ◽  
Hela Cell ◽  
Antiproliferative Activity ◽  
Dna Cleavage ◽  
In Vitro Cytotoxicity ◽  
Hela Cell Lines ◽  
Mcf 7

Four new binuclear nickel(ii) metallates showed promising antiproliferative activity against MCF-7 and HeLa cell lines and were much less toxic against HaCaT.

scholarly journals Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion

2010 ◽  
Vol 151 (36) ◽  
pp. 1455-1460 ◽  
Author(s):  
Gábor Somlyai ◽  
Miklós Molnár ◽  
Gábor Laskay ◽  
Mariann Szabó ◽  
Tamás Berkényi ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Biological Significance ◽  
Human Melanoma ◽  
Naturally Occurring ◽  
Ht 29 ◽  
Mcf 7

A felszíni vizekben a deutérium (D) koncentrációja több mint 16 mmol/l (150 ppm), az élő szervezetekben 10 mmol/l fölötti. A csökkentett deutériumtartalmú (30±5 ppm) vízzel folyó kutatások során korábban azt tapasztalták, hogy a deutériummegvonás gátolta a sejtosztódást in vitro különböző tumoros sejtvonalakban (PC-3, humán prosztatatumor; MDA, humán emlőtumor; HT-29, humán vastagbéltumor; M14, humán melanoma). A csökkentett deutériumtartalmú víz tumorregressziót idézett elő humán eredetű tumorral xenotranszplantált, immunszuppresszált egerekben (MDA és MCF-7 humán emlőtumor, PC-3 prosztatatumor), és apoptózist indukált in vitro és in vivo . A csökkentett deutériumtartalmú víz (25±5 ppm) részleges vagy teljes tumorregressziót idézett elő spontán tumoros kutyákban és macskákban. A készítményt 1999-ben daganatellenes állatgyógyszerként törzskönyvezték (Vetera-DDW-25 A.U.V., 13/99 FVM). Injekciós változatát klinikai vizsgálatban sikeresen tesztelték. Az Országos Gyógyszerészeti Intézet 5621/40/95 számú engedélye alapján, a GCP-elvek betartásával lefolytatott randomizált, kettős vak elrendezésű humán fázis II klinikai vizsgálat szignifikáns különbséget igazolt a kontroll- és a kezelt csoport között a vizsgált paraméterek vonatkozásában. Egyéves utánkövetés során a csökkentett deutériumtartalmú víz szignifikánsan csökkentette a prosztatatumoros betegek halálozási arányát, miközben a túlélés hosszát szignifikánsan növelte. Az eredmények azt igazolják, hogy a sejtek képesek szabályozni a deutérium/hidrogén (D/H) arányát és ennek változtatásával elindítani bizonyos molekuláris folyamatokat, amelyeknek kulcsszerepük van a sejtciklus szabályozásában. Feltételezzük, hogy nem az intracelluláris pH változása, hanem az azt kísérő D/H arány változása adja meg a sejteknek a jelet az S-fázisba lépéshez. A D-koncentráció csökkenése beavatkozik a szignáltranszdukciós folyamatokba, így idézve elő a tumor regresszióját. A D szerepének felismerése a sejtosztódás szabályozásában új lehetőségeket nyit meg a daganatterápia és a megelőzés területén, hozzájárulva ezzel a jelenlegi daganatellenes terápiák hatékonyságának növeléséhez.

scholarly journals THE CYTOTOXIC EFFECT OF CHELIDONIUM MAJUS IN VITRO

2015 ◽  
Vol 8 (2) ◽  
Author(s):  
Vladimíra Tomečková ◽  
Veronika Tkáčová ◽  
Peter Urban ◽  
Marek Stupák
Keyword(s):  
Tumor Cells ◽  
Hela Cells ◽  
Antiproliferative Activity ◽  
Cytotoxic Effect ◽  
Lymphoblastic Leukemia ◽  
Mammary Adenocarcinoma ◽  
Chelidonium Majus ◽  
Mcf 7 ◽  
Lipophilic Substances

The effect of aqueous and ether Chelidonium majus haulms extract on cervical HeLa tumor cells, mammary adenocarcinoma MCF 7 tumor cells and acute lymphoblastic leukemia CEM tumor cells in vitro have been studied. The purpose of this research was to compare the effect of aqueous and ether Chelidonium majus haulms extract on selected tumor cells. Colorimetric MTT assay have been used for the study of the antiproliferative effect of aqueous and ether haulms extract of Chelidonium majus on cell viability in vitro. The results of the experiments have shown the cytotoxic effect of the aqueous and the ether Chelidonium majus haulms extract on the individual tumor cells. The aqueous Chelidonium majus haulms extract was the most effective on CEM cells, it was less effective on MCF 7 cells and it was the least effective on HeLa cells. The ether haulms extract of Chelidonium majus was the most effective at all of studied concentrations on CEM cells and MCF 7 cells in comparison with HeLa cells, where it was significantly effective only at the highest concentration. Aqueous and ether haulms extract of Chelidonium majus tested in vitro indicated their cytotoxic activity. Both haulms extract of Chelidonium majus were more efficient on CEM cells. It is assumed that higher antiproliferative activity of ether haulms extract of Chelidonium majus is the result of higher antiproliferative activity of lipophilic substances. The lipophilic substances pass through membrane and bind to various proteins and change their biological activity.

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