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Home / Archives for Anticancer Research

Possible Biological and Clinical Applications of Phenothiazines

  • Authors: Amaral L, Csonka Á, Molnar J, Spengler G, Varga B
  • Publication Year: 2017
  • Journal: Anticancer Research
  • Link: https://www.ncbi.nlm.nih.gov/pubmed/29061777

Phenothiazines have been used in many areas of medicine, mainly in psychopharmacology. These compounds are able to effectively inhibit dopamine, histamine, serotonin, acetylcholine, and α-adrenergic receptors; thus, their effect and side-effect profiles are extremely diverse. Besides their antipsychotic activity, phenothiazines have a significant antimicrobial effect as well, since they can enhance the bactericidal function of macrophages and inhibit efflux pumps. They are also able to eliminate bacterial resistance plasmids and destroy bacteria by their membrane-destabilizing effect. Their antiviral, antiprotozoal, antifungal, and antiprion activities have also been described. Phenothiazines have also been proven to destroy cancer cells and sensitize them to chemotherapy. Anti-angiogenesis and anticancer stem cell activities have also been reported, and they might be applied as adjuvants in the treatment of infections and tumors in the future. Finally, phenothiazines can also be effective in the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.
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Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein.

  • Authors: Amaral L, Molnar J, Spengler G, Viveiros M
  • Journal: Anticancer Research
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Thioridazine+induces+apoptosis+of+multidrug-resistant+mouse+lymphoma+cells+transfected+with+the+human+ABCB1+and+inhibits+the+expression+of+P-glycoprotein

AIM:
Chlorpromazine has activity against a large variety of cancer types. However, this phenothiazine produces a plethora of serious side-effects. We have studied thioridazine (TZ), a phenothiazine neuroleptic that is much milder, for activity against multidrug-resistant (MDR) cancer cells, as well as against the overexpressed ABCB1 transporter (P-glycoprotein) that is the cause for the MDR phenotype of these cancer cells.
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Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis.

  • Authors: Amaral L, Handzlik J, Kiec-Kononowicz K, Molnar J, Ocsovszki I, Spengler G, Viveiros M
  • Journal: Anticancer Research
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Modulation+of+multidrug+efflux+pump+activity+by+new+hydantoin+derivatives+on+colon+adenocarcinoma+cells+without+inducing+apoptosis

BACKGROUND:
Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin.
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Rapid, laser-induced conversion of 20-hydroxyecdysone and its diacetonide — experimental set-up of a system for photochemical transformation of bioactive substances.

  • Authors: Alexandru T, Amaral L, Andrei IR, Boni M, Danko B, Hunyadi A, Militaru A, Nastasa V, Pascu ML
  • Journal: Anticancer Research
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/22493361

BACKGROUND:
Photochemical transformation of certain bioactive compounds for the purpose of obtaining derivatives with increased bioactivity is a prospective area of synthetic chemistry. Ecdysteroids, analogs of the insect molting hormone, which can also exert several beneficial effects in mammals including humans, contain an enone moiety in their B ring, and, as such, are good candidates for photochemical transformations.
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In vitro cytotoxic activity of novel protoflavone analogs – selectivity towards a multidrug resistant cancer cell line.

  • Authors: Amaral L, Chang FR, Chuang DW, Danko B, Hunyadi A, Martins A, Molnar J, Wang HC, Wu YC
  • Journal: Anticancer Research
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=In+vitro+cytotoxic+activity+of+novel+protoflavone+analogs+%E2%80%93selectivity+towards+a+multidrug+resistant+cancer+cell+line

BACKGROUND:
Protoapigenone (PA), a natural flavonoid possessing an unusual p-quinol moiety on its B ring, is a prospective novel lead compound against cancer currently in development, together with WYC0209, a potent synthetic PA analog. Structure activity relationships (SAR) concerning different 1′-O-alkyl side-chains were also studied on two sets of derivatives.
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About GHTM

GHTM is a R&D Unit that brings together researchers with a track record in Tropical Medicine and International & Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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