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Home / Archives for Molnar J

Molnar J

Why and how thioridazine in combination with antibiotics to which the infective strain is resistant will cure totally drug-resistant tuberculosis.

  • Autores: Amaral L, Molnar J
  • Ano de Publicação: 2012
  • Journal: Expert Review of Anti-infective Therapy
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Why+and+How+Thioridazine+in+combination+with+antibiotics+to+which+the+infective+strain+is+resistant+will+cure+totally+drug+resistant+tuberculosis+(TDR+TB)

Over a period of 14 years, the authors have studied thioridazine, an old neuroleptic, that has been shown to have in vitro activity against intracellular Mycobacterium tuberculosis, regardless of its antibiotic resistance status, thioridazine cures infected mice of antibiotic-susceptible and multidrug-resistant tuberculosis (TB) infections and, when used in combination with antibiotics used for therapy of TB, renders the organism significantly more susceptible.
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Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

  • Autores: Amaral L, Dasgupta A, Dastidar SG, Jeyaseeli L, Molnar J
  • Ano de Publicação: 2012
  • Journal: European Journal of Clinical Microbiology & Infectious Diseases
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Evidences+of+Significant+Synergism+between+Antibiotics+and+the+Antipsychotic+Antimicrobial+Drug+Flupenthixol.

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella.
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The in vitro activity of products formed from exposure of chlorpromazine to a 266nm laser beam against species of mycobacteria of human interest

  • Autores: Alexandru T, Amaral L, Armada AM, Boni M, Danko B, Dinache A, Hunyadi A, Machado D, Molnar J, Nastasa V, Pascu ML, Ramos J, Viveiros M
  • Ano de Publicação: 2013
  • Journal: In vivo
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/23988894

Chlorpromazine (CPZ) was exposed to a 266 nm laser beam for different periods of time ranging from minutes to 24 h. At intervals, the products from irradiation were evaluated by thin-layer chromatography (TLC) and evaluated for their activity against mycobacteria of human interest (Mycobacterium tuberculosis, M. avium, M. intracellulare and their corresponding reference strains or clinical isolates).
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Quorum Sensing Inhibition by Phenothiazines and Related Compounds.

  • Autores: Amaral L, Molnar J, Schelz Z, Szabó MA, Szegedi E, Varga ZG
  • Ano de Publicação: 2011
  • Journal: Letters in Drug Design & Discovery
  • Link: https://apps.webofknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=22&SID=Y2ytOr2frNCuRlReLtM&page=1&doc=1

A quorum is the smallest number of people able to organize the decisions concerning functional activity. Similarly microbes use chemical signal molecules to make population size-dependent “decisions” by changing their gene regulations.
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Biological activity of twenty-three hydantoin derivatives on intrinsic efflux pump system of Salmonella enterica serovar Enteritidis NCTC 13349.

  • Autores: Amaral L, Evaristo M, Handzlik J, Kiec-Kononowicz K, Machado L, Molnar J, Spengler G, Viveiros M
  • Ano de Publicação: 2011
  • Journal: In vivo
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Biological+activity+of+twenty-three+hydantoin+derivatives+on+intrinsic+efflux+pump+system+of+Salmonella+enterica+serovar+Enteritidis+NCTC+13349.

BACKGROUND:
Hydantoin derivatives have important biochemical and pharmacological properties. In the present study, 23 hydantoin compounds were evaluated for their efflux-modulating effects in Salmonella enterica serovar Enteritidis NCTC 13349 using real-time fluorimetry based on the intracellular accumulation of ethidium bromide (EB), a universal substrate of efflux pumps.
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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.

  • Autores: Amaral L, Molnar J, Spengler G, Viveiros M
  • Ano de Publicação: 2011
  • 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.

  • Autores: Amaral L, Handzlik J, Kiec-Kononowicz K, Molnar J, Ocsovszki I, Spengler G, Viveiros M
  • Ano de Publicação: 2011
  • 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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Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators.

  • Autores: Amaral L, Bombicz P, Egyed O, Hajos G, Jemnitz K, Molnar J, Nagy I, Riedl Z, Takács D
  • Ano de Publicação: 2012
  • Journal: Bioorganic & Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Selective+hydroboration+of+dieneamines.+Formation+of+hydroxyalkylphenothiazines+as+MDR+modulators

N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH(3) × Me(2)S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors.
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Karavilagenin C derivatives as antimalarials.

  • Autores: Ferreira MJ, Lopes D, Molnar J, Mulhovo S, Ramalhete C, Rosário VE
  • Ano de Publicação: 2011
  • Journal: Bioorganic & Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Karavilagenin+C+derivatives+as+antimalarials

Karavilagenin C (1), a cucurbitane-type triterpenoid, previously isolated from the aerial parts of Momordica balsamina, was acylated with different alkanoyl, aroyl and cinnamoyl chlorides/anydrides, yielding ten new mono or diesters, karavoates F (7) and H-P (8-16).
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In vitro cytotoxic activity of novel protoflavone analogs – selectivity towards a multidrug resistant cancer cell line.

  • Autores: Amaral L, Chang FR, Chuang DW, Danko B, Hunyadi A, Martins A, Molnar J, Wang HC, Wu YC
  • Ano de Publicação: 2012
  • 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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