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Biomedical subjects

M Rambaldi

Publications and source records attributed to M Rambaldi.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones.

The synthesis of 3-(5-imidazo]2,1-blthiazolylmethylene)-2-indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-1(2,6-dimethylimidazo[2,1-bJ-thiazol-5-yl)methylenel-5-methoxy-2-indolinone was the most active of the whole series.

Animals↗
PubMedDate not supplied

Reduction of adriamycin cardiotoxicity by a new cardiotonic agent.

Recently several non catecholamine, non glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate anthracycline toxicity, we have previously reported that these compounds reduced the negative inotropic effect of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent synthesized and studied by us: 2,3-Dihydro-6- (2,5-dimethoxyphenyl) imidazo [2,1-b]thiazole (VA-5), the most active of a series of 32 compounds with imidazo [2,1-b] thiazole and thiazoline moiety. Exposure for 60 to adriamycin (100 micrograms/ml) of electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions, caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of adriamycin are antagonized by VA-5 (100 micrograms/ml).

Animals↗
PubMedDate not supplied

Synthesis and cytotoxic activity of a new alkylating derivative of dipyridamole.

Synthesis of 2,6-Bis[bis(2-chloroethyl) amino]-4,8-dipiperidinopyrimido[5,4-d] pyrimidine, a derivative of dipyridamole, was carried out by treating dipyridamole with thionyl chloride. Cytotoxic activity of this compound was assessed using cultured P388 leukaemia cells and HeLa cells. The compound inhibited the colony-forming ability of HeLa cells and showed a cytotoxicity on P388 cells comparable to that of other alkylating drugs (chlorambucil and CCNU).

Alkylating Agents↗
PubMedDate not supplied

New alkylating agents: butyrophenone derivatives.

The antimitotic properties associated with the bis (2-chloroethyl) amino group are well known, a number of compounds bearing this group being of therapeutic interest. The choice of a suitable supporting moiety for this group is important. Our experiments on a butyrophenone derivative, ketocaine, which possesses local anesthetic activity, showed that this drug is able to modify the oxygen consumption by tissues with prevailing anaerobic metabolism and to inhibit the mitotic activity of human lymphocytes in culture stimulated by phytohemagglutinin. These observations prompted us to prepare compounds by the general formula reported in Tables I and II. All compounds were tested in mice implanted i.p. with 10(6) Ehrlich ascites tumour cells. After 24 h the animals were treated with a single dose of the compound. The antitumor activity was correlated with: position (2, 4) and length (n = 0-2) of the chain with carbonyl group; presence (R' = H, ND2) and position (2, 4) of nitro group; monofunzional or bifunzional compound. Some of these show a potent antitumor activity.

Alkylating Agents↗