Bis-pyridoquinolines as new bifunctional intercalators for DNA.

With the aim of obtaining new bifunctional intercalators for DNA, a new series of bis-pyridoquinolines were synthesized by joining two tricyclic planar moieties through a flexible chain. For preparing the corresponding potential monofunctional intercalators also a series of mono-pyridoquinolines were prepared by chemical synthesis by joining the same chromophore with a flexible side-chain. The melting profiles of the complexes between two bis-pyridoquinolines and DNA showed two different thermal transitions supporting the bis-intercalation of the ligand with the macromolecule. On the other hand, two mono-pyridoquinolines showed only one transition in the melting profile indicating a behaviour consistent with a mono-intercalation. The antiproliferative activity was tested in terms of DNA synthesis inhibition in Ehrlich ascite tumor cells; the examined bis-intercalating agent showed to be much more active than the tested mono-intercalating compound.

Substituted 4,7-dihydroxyindoles and related quinonoid derivatives as potential antimicrobial agents.

The antimicrobial activity of some 4,7-dihydroxyindole derivatives and indole-4,7-quinones was examined by determining the MIC against selected typical microorganisms (bacteria and fungi). A few of the compounds examined showed only a feeble inhibitory effect against some Gram-positive strains. Activity seems to be correlated with the lipophilic character of the molecules; in fact, all compounds containing a strong hydrophilic group, like a carboxyl, proved completely inactive.

Deep controlled hypotension with sodium nitroprusside in the surgical treatment of intracranial arterial aneurysms.

The authors report 73 cases of intracranial arterial aneurysms operated on under deep controlled hypotension--i.e. hypotension below 60 mmHg of systolic arterial pressure (s.a.p.)--. Deep hypotension was induced by Sodium Nitroprusside (SNP). No problems were encountered in order to reach or to maintain deep hypotension. SNP showed to be an easy hypotensive agent, without toxicity at the recommended dosage. Fifty-nine patients were operated on between 40 and 25 mmHg of s.a.p. In 55 patients deep hypotension lasted for 30 minutes or more, reaching 2 hours in 3 patients. Surgical results were excellent, in regard either to the control of bleeding, either to the dissection of the aneurysm. Clinical results were evaluated by comparison with 146 patients operated on under normal pressure (group of control); no complications were clearly related to deep hypotension per se. However, the authors stress the risks of deep hypotension in early surgery, due to the possible association to vascular spasm.

Antimicrobial properties of some 3-acyl-4,7-disubstituted indoles.

In continuation of research on indole derivatives as potential chemotherapeutic agents, the antimicrobial properties of some 4,7-disubstituted 3-acylindoles were studied; the derivatives tested were 4,7-dimethoxy-, 4-hydroxy-7-methoxy-, 4,7-dihydroxyindoles and indole 4,7-quinones. Only the dihydroxy compounds (V a-c) proved active against certain bacterial strains. In order to test whether the action mechanism was analogous to that of mitomycin, a series of experiments was carried out to study the formation of complexes with DNA. It was found that only the substances with antimicrobial activity can form complexes, and it is therefore suggested that the action mechanism involves interference with cellular DNA.