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Biomedical subjects

M Rambaldi

Publications and source records attributed to M Rambaldi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Thienylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase.

The synthesis of 6-substituted 5-(thienylvinyl)imidazo[2,1-b]thiazoles and 6-thienylimidazo[2,1-b]thiazoles is reported. These compounds were tested as specific inhibitors of the NADH: ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. The 6-thienylimidazo[2,1-b]thiazoles were more potent in mammalian than in nematode mitochondria and had an average titer of 0.11 mM for 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole (10). This compound is noncompetitive with the ubiquinone substrate and interacts with a site which is mutually exclusive with that of rotenone but nonexclusive with that of piericidin and several other inhibitors of NADH dehydrogenase. In the series of 5-(thienylvinyl)imidazothiazoles, the hydrobromide of (E)-6-chloro-5-(2-thienylvinyl)imidazo[2,1-b]thiazole (E-5.HBr) was found to be more potent as an inhibitor of the NADH:UBQ activity (IC50 = 15-17 microM) than the 6-thienylimidazoles such as 10. The inhibitory action of E-5.HBr and its analogs is different from that of compound 10 as indicated by the mutual exclusivity with other inhibitors and the relative inhibition of the activity with various electron acceptors.

Animals↗
PubMed1994

Thienylvinylindoles as inhibitors of mitochondrial NADH dehydrogenase.

In connection with a previous study, new phenylindoles bearing a 2- or 3-thienyl group were synthesized and tested as specific inhibitors of mitochondrial NADH dehydrogenase. The position of the phenyl ring and the geometrical configuration play an important role in the activity and specificity of these derivatives. In order to study the mechanism of action of these thienylvinylindoles, their activity was compared with that of known inhibitors in a new test employing exogenous quinones.

Animals↗
PubMed1993

Potential antitumor agents. XX (1). 6-Anilinoimidazo[2,1-b]thiazoles.

The synthesis of 6-anilinoimidazo[2,1-b]thiazoles, related to the well-known antitumor agent amsacrine, is reported. The cytotoxic activity of the new compounds was evaluated on HeLa cells. Compound 3a, the most closely related to amsacrine, was significantly active.

Antineoplastic Agents↗
PubMed1993

Translation of the placenta growth factor mRNA is severely affected by a small open reading frame localized in the 5' untranslated region.

The recently identified placenta growth factor gene (PIGF) code for a protein related to the vascular permeability factor (VPF). We present evidence indicating that expressing of this gene could be regulated at the post-transcriptional level. The region upstream to the coding region of PIGF mRNA contains a small open reading frame (ORF), potentially coding for a peptide of 15 amino acids. The translation of different constructs in reticulocyte and wheat germ lysates as well as in COS-1 and CV-1 cells indicates that this short region is a translational inhibitory element since mutations in its two potential initiator codons increase PIGF synthesis in vivo. Using RNAse protection assay, we demonstrate that the PIGF mRNAs obtained from human term placenta and JEG choriocarcinoma cell line have a complete 5' untranslated region and, consequently, also the above mentioned small ORF. Finally, the analysis of a bovine PIGF genomic clone reveals that this small ORF is strongly conserved with respect to both putative peptide sequences and distance from the PIGF coding region.

Amino Acid Sequence↗
PubMed1993

Potential antitumor agents. 23.(1) Cytotoxic and differentiating activity of compounds related to hexamethylenebisacetamide.

The synthesis of potential differentiating agents related to hexamethylenebisacetamide (HMBA) is reported. 1,6-Bis(3,3-dimethyl-2-oxo-2,3-dihydroindol-1-yl)hexane (4) and 1,6-bis(4-carbamoyl-thiazol-2-yl)hexane (9) were not soluble enough to allow biological testing. For this reason the dipotassium salt (10) of 1,6-bis(4-carboxy-thiazol-2-yl)hexane (11) was prepared. The salt 10, tested in the human rhabdomyosarcoma cell line (RMZ) and in the murine Friend erythroleukemia cells (MEL), proved more cytotoxic than HMBA, but was devoid of differentiating activity. Compounds 4, 9, 10 and 11, tested on HeLa cells (in vitro) and on Ehrlich ascites (in vivo) did not show antitumor activity.

Acetamides↗
PubMed1992

Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex.

We cloned two homeobox genes, Emx1 and Emx2, related to empty spiracles, a gene expressed in very anterior body regions during early Drosophila embryogenesis, and studied their expression in mouse embryos. Emx1 expression is detectable from day 9.5 of gestation whereas Emx2 appears to be already expressed in 8.5 day embryos. Both genes are expressed in the presumptive cerebral cortex and olfactory bulbs. Emx1 is expressed exclusively there, whereas Emx2 is also expressed in some neuroectodermal areas in embryonic head including olfactory placodes in earlier stages and olfactory epithelia later in development.

Amino Acid Sequence↗
PubMed1991

Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5' end of HOX1 locus on chromosome 7.

We isolated and mapped the human homeobox gene EVX1. This gene encodes a protein of 407 amino acid residues containing a homeodomain closely related to the Drosophila even-skipped (eve) segmentation gene of the pair-rule class. EVX1 belongs to a small family of vertebrate eve-related homeobox genes including human EVX1 and EVX2 genes, their murine homologs, Evx 1 and Evx 2, and the frog Xhox-3 gene. We previously reported that EVX2 is localized at the 5' end of the HOX4 locus on chromosome 2. We show here that EVX1 is localized at the 5' end of the HOX1 locus on chromosome 7, 48 kb upstream from the most 5' of the eleven HOX1 genes, namely HOX1J. Both EVX genes are transcribed in an opposite orientation as compared to that of adjacent HOX genes. Human HOX1 and HOX4 complex loci appear to be both closely linked to a homeobox gene of the EVX family.

Amino Acid Sequence↗
PubMed1991

A case of portal thrombosis arisen after treatment with dihydroergotamine.

We describe the case of a 42 year old woman with abdominal pain, ascites, and splenomegaly after having taken dihydroergotamine continuously for three months due to frequent hemicranic episodes. The celiac-mesenteric angiography demonstrated diffuse thrombosis of splenic, superior mesenteric and portal veins. No surgical intervention was possible. We believe that it is possible that dihydroerogotamine, a hydrogenated derivative of ergotamine, inasmuch as it is capable of causing peripheral vasoconstriction, intimal lesions, arterial and venous thrombi, was also the cause of our patient's portal thrombosis. We therefore suggest the minimum effective amount of the drug be utilized to achieve the relief of cephalalgia.

Adult↗
PubMed1991

Synthesis and analgesic activity of 1-(N-methylanilinoethyl)indoles.

The synthesis of two series of 1-(N-methylanilinoethyl)indoles is reported. The first arises from the N-alkylation of indole-3-acetic acid or its methylester, while the second was prepared by means of the Witting reaction on the appropriate aldehyde. The compounds were tested in mice (hot plate test and phenyl-p-benzoquinone induced writhing test) for their analgesic activity. None of the compounds was significantly active in the hot plate test. However, N-methylanilinoethyl 1-(N-methylanilinoethyl)-3-indolylacetate (7) was the most active one in the phenyl-p-benzoquinone induced writhing test, which indicates that 7 has a peripheral analgesic effect.

Analgesics↗