scholarly journals 3-Aryl-4-nitrobenzothiochromans S,S-dioxide: From Calcium-Channel Modulators Properties to Multidrug-Resistance Reverting Activity

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1056 ◽  
Author(s):  
Matteo Micucci ◽  
Maurizio Viale ◽  
Alberto Chiarini ◽  
Domenico Spinelli ◽  
Maria Frosini ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Tumor Cell ◽  
Organic Compounds ◽  
Ex Vivo ◽  
Pharmacological Properties ◽  
Tumor Cell Lines ◽  
Research Groups ◽  
Biological Profile ◽  
Biological Interest

Our research groups have been involved for many years in studies aimed at identifying new active organic compounds endowed with pharmacological properties. In this work, we focused our attention on the evaluation of cardiovascular and molecular drug resistance (MDR) reverting activities of some nitrosubstituted sulphur-containing heterocycles. Firstly, we have examined the effects of 4-nitro-3-(4-methylphenyl)-3,6-dihydro-2H-thiopyran S,S-dioxide 5, and have observed no activity. Then we have extended our investigation to the 3-aryl-4-nitrobenzothiochromans S,S-dioxide 6 and 7, and have observed an interesting biological profile. Cardiovascular activities were assessed for all compounds using ex vivo studies, while the MDR reverting effect was evaluated only for selected compounds using tumor cell lines. All compounds were shown to affect cardiovascular parameters. Compound 7i exerted the most effect on negative inotropic activity, while 6d and 6f could be interesting molecules for the development of more active ABCB1 inhibitors. Both 6 and 7 represent structures of large possible biological interest, providing a scaffold for the identification of new ABCB1 inhibitors.

Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo

1999 ◽  
Vol 139 (1) ◽  
pp. 115-119 ◽  
Author(s):  
Diána Szabó ◽  
Gábor Szabó ◽  
Imre Ocsovszki ◽  
Adorján Aszalos ◽  
József Molnár
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cell ◽  
Cell Lines ◽  
Ex Vivo ◽  
Tumor Cell Lines ◽  
Anti Psychotic

scholarly journals Characterization and Drug Resistance Patterns of Ewing's Sarcoma Family Tumor Cell Lines

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80060 ◽  
Author(s):  
William A. May ◽  
Rita S. Grigoryan ◽  
Nino Keshelava ◽  
Daniel J. Cabral ◽  
Laura L. Christensen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Cell ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Tumor Cell Lines ◽  
Resistance Patterns

Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cell lines characterized for EGFR expression and K-ras mutation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14583-e14583 ◽  
Author(s):  
J. Barriere ◽  
J. Fischel ◽  
P. Formento ◽  
N. Renée ◽  
M. Francoual ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Human Cancer ◽  
Tumor Cell Lines ◽  
Ras Mutation ◽  
Egfr Expression ◽  
Mutational Status

e14583 Background: Mutated K-ras protein is a strong predictive factor of cetuximab resistance, bypassing the classical direct inhibitory effect on epidermal growth factor receptor (EGFR) signaling. However, cetuximab is also able to mediate ADCC, which may be part of the clinical response. The aim of this ex-vivo study was to quantify cetuximab-mediated ADCC on various human cancer cell lines characterized for EGFR-expression and K-ras mutation. Methods: Two K-ras mutated cell lines over-expressing EGFR and resistant to anti-EGFR tyrosine kinase inhibitor were tested (Capan-1 and Capan-2, pancreatic), along with 2 K-ras wild-type cell lines over- expressing EGFR (CAL166, head and neck; A431, epidermoid carcinoma) and an EGFR-negative cell line (OCM1, uveal melanoma). The tested monoclonal antibodies (mAbs) were: cetuximab (Merck, anti-EGFR IgG1 mAb), panitumumab (Amgen, anti-EGFR IgG2 mAb), and as a negative control, rituximab (Roche, IgG1 anti-CD20 mAb). ADCC (51Cr release assay) was performed using freshly- isolated peripheral blood mononuclear cells from a healthy donor. Results were expressed as % of potentially maximum 51Cr release. Results: Cetuximab mediates ADCC against EGFR-over-expressing cell lines CAL166 (38.4 ± 3.1 %), A431 (13.5 ± 1.7 %), Capan-1 (31.2 ± 0.8 %) and Capan-2 (27.8 ± 8.6 %) irrespective of the K-ras mutational status, but not against EGFR-negative OCM-1 (6.2 ± 1 %). Conversely, unlike IgG1 cetuximab, the anti-EGFR IgG2 panitumumab and the irrelevant antibody rituximab were both unable to induce significant ADCC (< 10 % on all tested cell lines). Conclusions: Cetuximab-mediated ADCC is independent of the K-ras mutational status of the tumor cell lines. Present data suggest that cetuximab may remain of clinical interest in K-ras-mutated patients. Immunostimulation, as well as new generation anti-EGFR mAbs with improved ability to induce ADCC, may be promising in the management of K-ras-mutated patients. No significant financial relationships to disclose.

scholarly journals The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings.

2002 ◽  
Vol 49 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Maria M Bontemps-Gracz ◽  
Agnieszka Kupiec ◽  
Ippolito Antonini ◽  
Edward Borowski
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cell ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Heterocyclic Ring ◽  
Tumor Cell Lines ◽  
Human Tumor Cell Lines

Two recently synthesized groups of acridine cytostatics containing fused heterocyclic ring(s): pyrazoloacridines (PAC) and pyrazolopyrimidoacridines (PPAC) were tested in regard to their in vitro cytotoxic activity towards a panel of sensitive and resistant human tumor cell lines. The obtained results corroborate our earlier hypothesis on the essential role of heterocyclic ring fused to the acridine moiety in the ability of acridine cytostatics to overcome multidrug resistance of tumor cells. The presence, location and kind of substituents considerably influenced both the cytotoxic activity of the derivatives and their ability to overcome multidrug resistance. The same factors also affected the cytostatics ability to differentiate between tumor cell lines with various types of drug exporting pumps.

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