IHMT

Instituto de Higiene e Medicina Tropical

Home / Archives for Amaral L

Amaral L

Quorum Sensing Inhibition by Phenothiazines and Related Compounds.

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.
Ler mais

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.
Ler mais

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.
Ler mais

The added effect of thioridazine in the treatment of drug-resistant tuberculosis.

The review by Grosset et al. in a recent issue of the
Journal is highly interesting, and rightly pictures a
bright horizon for the improved treatment of tuberculosis. However, there are alternative compounds
that can already provide considerable relief in compassionate
application of treatment for multidrugr
esistant and extensively drug-resistant tuberculosis
(MDR/XDR-TB) in the short term, and may offer an
important additional effect in treatment regimens due
to a special working mechanism, such as effl ux pump
inhibition.
Ler mais

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.
Ler mais

Mechanisms of Antibiotic Resistance in Salmonella: Efflux Pumps, Genetics, Quorum Sensing and Biofilm Formation.

Multidrug resistance (MDR) to antibiotics presents a serious therapeutic problem in the treatment of bacterial infections. The importance of this mechanism of resistance in clinical settings is reflected in the increasing number of reports of multidrug resistant isolates. In Salmonella enterica, the most common etiological agent of food borne salmonellosis worldwide, MDR is becoming a major concern.
Ler mais

Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance.

BACKGROUND:
Active efflux systems and reduced cell-wall permeability are considered to be the main causes of mycobacterial intrinsic resistance to many antimicrobials. In this study, we have compared the Mycobacterium smegmatis wild-type strain mc2155 with knockout mutants for porins MspA (the main porin of M. smegmatis) and MspC, the efflux pump LfrA (the main efflux pump system of M. smegmatis) and its repressor LfrR for their ability to transport ethidium bromide (EtBr) on a real-time basis.
Ler mais

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.
Ler mais

Inhibition of drug efflux in mycobacteria with phenothiazines and other putative efflux inhibitors.

Mycobacteria are responsible for some of the oldest diseases known to man, usually associated with high morbility and mortality rates. An example is tuberculosis (TB), a major public health problem that accounts for eight million new cases each year.
Ler mais