Search results for " Antitumor"

Rational design of allosteric modulators of the aromatase enzyme: An unprecedented therapeutic strategy to fight breast cancer.

2019

Estrogens play a key role in cellular proliferation of estrogen-receptor-positive (ER+) breast cancers (BCs). Suppression of estrogen production by competitive inhibitors of the enzyme aromatase (AIs) is currently one of the most effective therapies against ER + BC. Yet, the development of acquired resistance, after prolonged treatments with AIs, represents a clinical major concern. Serendipitous findings indicate that aromatase may be non-competitively inhibited by clinically employed drugs and/or industrial chemicals. Here, by performing in silico screening on two putative allosteric sites, molecular dynamics and free energy simulations, supported by enzymatic and cell-based assays, we id…

SYNTHESIS AND ANTITUMOR ACTIVITY OF 3-[2-PHENYL-1,3-THIAZOL-4-YL]-1H-7-AZAINDOLES

2010

Pyrrolo[2,1-d][1,2,3,5]tetrazine-4(3H)-ones, a new class of azolotetrazines with potent antitumor activity.

2003

Pyrrolo[2,1-d][1,2,3,5]tetrazinones 10a-o, compounds that hold the deaza skeleton of the antitumor drug temozolomide, were prepared by reaction of 2-diazopyrroles 9 and isocyanates. Such a synthetic route represents, among those leading to azolotetrazinones reported so far, the only possible one since attempts to cyclize to the title ring system 2-amino-1-carbamoylpyrroles 11 or the mono substituted 2-triazenopyrrole 12 failed. Compounds 10 were screened at the National Cancer Institute (NCI) for their activity against a panel of about 60 human tumor cell lines. Most of them possess remarkable antineoplastic activity having GI(50) values in the low micromolar or sub-micromolar range and rea…

Synthesis of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one

2011

Derivatives of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one were prepared in four steps starting from substituted benzonitriles bearing a functionalized amino group in the adjacent position. The unsubstituted- and the dimethoxy-pyrrolizinoindolones 5a and 5b exhibited modest activity against the HL-60(TB) human leukemia cell line, whereas the N-methylated dimethoxy-pyrrolizinoindolone 6b showed to be selective against MOLT-4 leukemia, A549/ATCC, HOP-92, and NCI-H460 non-small cell lung cancer, and CAKI-1 renal cancer cell lines.

A computational study to explore the molecular mechanisms behind the antiproliferative activity of Nortopsentin derivatives

2018

Saponins from the Roots of Nylandtia spinosa

2007

From the roots of Nylandtia spinosa, four new triterpene saponins, 3- O-beta- d-glucopyranosylpresenegenin 28- O-beta- d-galactopyranosyl-(1-->4)-[alpha- l-arabinopyranosyl-(1-->3)]-beta- d-xylopyranosyl-(1-->4)-[beta- d-apiofuranosyl-(1-->3)]-alpha- l-rhamnopyranosyl-(1-->2)-beta- d-fucopyranosyl ester ( 1), 3- O-beta- d-glucopyranosylpresenegenin 28- O-beta- d-galactopyranosyl-(1-->4)-[alpha- l-arabinopyranosyl-(1-->3)]-beta- d-xylopyranosyl-(1-->4)-alpha- l-rhamnopyranosyl-(1-->2)-beta- d-fucopyranosyl ester ( 2), 3- O-beta- d-glucopyranosylpresenegenin 28- O-beta- d-apiofuranosyl-(1-->4)-[beta- d-galactopyranosyl-(1-->2)]-beta- d-xylopyranosyl-(1-->4)-alpha- l-rhamnopyranosyl-(1-->2)-be…

Tumorigenic and metastatic activity of human thyroid cancer stem cells

2010

Abstract Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. We show that the tumorigenic capacity in thyroid cancer is confined in a small subpopulation of stem-like cells with high aldehyde dehydrogenase (ALDHhigh) activity and unlimited replication potential. ALDHhigh cells can be expanded indefinitely in vitro as tumor spheres, which retain the tumorigenic potential upon delivery in immunocompromised mice. Orthotopic injection of minute numbers of thyroid cancer stem cells recapitulates the behavior of the parental tumor, including the aggressive metastatic features of undifferentiated thyroid carcinomas, which are sustained by…

Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.

2015

Background Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting. Methods Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents. Results Cancer stem cells were extracted from liver metas…

Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease

2014

Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe. In the last decade, compelling evidence for the nutritional and health benefit potential of this cactus has been provided by academic scientists and private companies. Notably, its rich composition in polyphenols, vitamins, polyunsaturated fatty acids and amino acids has been highlighted through the use of a large panel of extraction methods. The identified natural cactus compounds and derivatives were shown to be e…

cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro

2013

A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.