New tetracyclic analogues of photochemotherapeutic drugs 5-MOP and 8-MOP: synthesis, DNA interaction, and antiproliferative activity.

The synthesis of new tetrahydrobenzo- and benzopsoralen derivatives carrying at position 5 or 8 of the furocoumarin moiety a methoxy, hydroxy, or dimethylaminopropoxy side chain is reported. The study of their photoantiproliferative activity and ability to induce erythema on guinea pig skin allows us to state that the derivatives carrying the dimethylaminopropoxy side chain exhibit a very interesting photobiological pattern. Indeed, if compared with the lead compounds 5-MOP and 8-MOP, they exert a higher cytotoxic activity devoid of significant skin phototoxicity.

Synthesis and biological evaluation of 1,2-disubstituted carbonucleosides of 6-substituted purine and 8-azapurine.

A series of new one two substituted carbonucleoside analogues (OTC), with the purine and 8-azapurine base linked through a methylene group at the cyclopentane ring, were synthesized and evaluated for their activity against a number of viruses and tumor cells in vitro.

Photobiological studies of new cyclopentene-psoralens.

Psoralen analogues bearing a cyclopentane ring fused to either the 4',5' double bond (compound 4) or the 3,4 double bond (compound 7) of the tricyclic furocoumarin structure were prepared. AM1 theoretical calculations performed for these compounds indicated that the electronic properties of their reactive double bonds were very similar to those of psoralen and its derivative 8-methoxypsoralen (8-MOP), though the overall molecular geometries were clearly different, particularly as regards the change in molecular curvature produced by the introduction of the cyclopentane ring. Compound 4 showed a capacity similar to that of 8-MOP to inhibit the growth of human cervix adenocarcinoma cells (HeLa) and to induce mutagenic effects, but it was definitely less phototoxic to skin than 8-MOP.

Phenylpiperazine derivatives with strong affinity for 5HT1A, D2A and D3 receptors.

Four 7-[3-(4-phenyl-1-piperazinyl)propoxy]coumarins were synthesized. The affinities of these compounds for DA (D2A, D3) and 5HT1A receptors were evaluated for their ability to displace [3H]-raclopride and [3H]-8-OH-DPAT respectively from their specific binding sites. The affinities of the target compounds were all in the nanomolar range and followed the order 5-HT1A > D2 > D3.

Synthesis and biological evaluation of 1,2-disubstituted carbonucleosides of 2-amino-6-substituted purine and 8-azapurine.

One, two-disubstituted carbocyclic nucleoside analogues bearing a 2-amino-6-substituted (chloro, hydroxy or amino) purine or 8-azapurine base were prepared by constructing the base about (+/-)-2-aminocyclopentane methanol, and their activities against a selection of viruses and tumor cells were determined in vitro.

AM1 theoretical study, synthesis and biological evaluation of some benzofuran analogues of anti-inflammatory arylalkanoic acids.

Using the semi-empirical quantum-mechanical method AM1, the molecular geometries of the arylalkanoic acids, indomethacin, naproxen and ibuprofen, were optimized and their frontier orbital charge distributions evaluated. Then, these molecular parameters were compared in order to identify structure-activity relationships and, on the basis of these, four benzofuran-3-acetic acids were designed as potential non-steroidal anti-inflammatory agents, and rapidly synthesized by a novel and easily generalized route. Notwithstanding the structural similarities between the synthesized compounds and the anti-inflammatory arylalkanoic acids, these compounds did not appreciably inhibit human platelet cyclooxygenase in vitro.

[Risk of the development of dementia after interruption of zidovudine treatment].

Background: Epidemiologic data suggest that zidovudine (ZDV) could prevent the AIDS dementia complex (ADC), but this hypothesis has been specifically studied.

Patients And Methods: We have reviewed the medical records of all patients with human immunodeficiency virus (HIV) infection admitted to our section between January 1990 and December 1993 who were diagnosed with ADC, and we have compared them to those of a control group with regard to the interruption of ZDV at least 3 months before. Controls were selected from the remaining HIV-related admissions, matched by calendar year, CD4-cell count and previous HIV-disease stage.

Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment.

Objective: To assess the features and therapeutic response of visual manifestations and cerebrovascular accidents (CVA) in giant cell (temporal) arteritis (GCA) and to identify the predictors for permanent visual loss (VL) and CVA in GCA.

Methods: Two hundred thirty-nine patients with biopsy-proven GCA were included in a retrospective multicenter study. Data on demographic, clinical, and laboratory features were collected.

Preliminary study of the potential vasodilator effects on rat aorta of centaurein and centaureidin, two flavonoids from Centaurea corcubionensis.

In this work, the potential vasorelaxant activity of centaurein and centaureidin, two flavonoids from Centaurea corcubionensis, were studied for the first time in rat aorta. Centaureidin (10 microM-0.1 mM) totally relaxed, in a concentration-dependent manner and with almost equal effectiveness, the contractions induced by NA (IC50 = 16.

Some new methyl-8-methoxypsoralens: synthesis, photobinding to DNA, photobiological properties and molecular modelling.

The tricyclic structure of known natural photochemotherapeutic drugs such as 8-methoxypsoralen and 5-methoxypsoralen is often taken as a model in the search of new photosensitizer agents with less phototoxic and mutagenic effects. This paper describes the synthesis, characterization, photobinding to DNA, photobiological properties and computational chemistry of some 8-methoxypsoralen derivatives bearing two or three methyl groups at the key positions of the two photoactive double bonds. Results showed that photoreactivity and photobiological behaviour depend on the pattern of methyl substitutions.

Amido analogs of mitoxantrone: physico-chemical properties, molecular modeling, cellular effects and antineoplastic potential.

To assess the effects of amido substitution in the side-chains of the anticancer drug mitoxantrone (MX) two analogs were synthesized, having hydroxyethylaminoacetyl- and hydroxyethylaminopropionyl- substituents at the nitrogens located at positions 1, 4 of the anthracenedione ring system. The novel derivatives exhibit DNA-affinity and redox properties similar to the parent drug. However, unlike MX, they are not able to stimulate DNA cleavage, as shown by alkaline elution experiments.

Synthesis and mass spectrometric behavior of some new nucleosides as potential anti-HIV agents.

The electron-impact (EI) mass spectrometric behaviour of a series of 8-aza-purines derivatized with hydroxymethylcyclopentane and exhibiting cis-trans isomerization in the cyclopentane ring has been studied in detail with the aid of metastable-ion data. Specific fragmentation processes, present in both EI and mass analysed ion kinetic energy spectra of molecular species, allow characterization of the different pairs of stereoisomers. Contrary to what is observed in the case of purine analogs, the presence of a nitrogen atom in position 8 strongly inhibits fragmentation processes related to the heterocycle.

4'-Methyl derivatives of 5-MOP and 5-MOA: synthesis, photoreactivity, and photobiological activity.

The synthesis and photobiological activity of four new 4'-methyl derivatives of 5-MOP (5-methoxypsoralen) and 5-MOA (5-methoxyangelicin), i.e., 4,4'-dimethyl-5-methoxypsoralen, 3,4'-dimethyl-5-methoxypsoralen, 4,4'-dimethyl-5-methoxyangelicin, and 3,4'-dimethyl-5-methoxyangelicin, are described.

Peptidyl anthraquinones as potential antineoplastic drugs: synthesis, DNA binding, redox cycling, and biological activity.

A series of new compounds containing a 9,10-anthracenedione moiety and one or two peptide chains at position 1 and/or 4 have been synthesized. The amino acid residues introduced are glycine (Gly), lysine (Lys), and tryptophan (Trp), the latter two in both the L- and D-configurations. The peptidyl anthraquinones maintain the ability of intercalating efficiently into DNA, even though the orientation within the base-pair pocket may change somewhat with reference to the parent drugs mitoxantrone (MX) and ametantrone (AM).

[Chronic monoarthritis caused by osteoid osteoma].

Osteoid osteoma is a nonmalignant tumour that rarely localizes intraarticularly. When this happens, the tumour provokes arthritis and its recognition is delayed from months to years. We report the case of a 34 year old man with a previously known HIV infection, but no evidence of immunosuppression.

Mixed sclerosing bone dystrophy. Report of a case and review of the literature.

A 63-year old woman was admitted because of hip pain. Radiographs showed multiple round and oval sclerotic lesions involving humeral heads, pelvis, vertebral bodies and both femoral bones. Diaphyseal periosteal proliferation was found in metatarsal bones.

Synthesis and cytostatic activity of some sulfamido-anthraquinones.

N-1- or 2-anthraquinonyl derivatives of p-methyl-, p-methoxy- and p-aminobenzenesulfonamides were synthesized and evaluated in vitro as antitumour agents. Only N-(1-anthraquinonyl)-p-methylbenzenesulfonamide (1) and -p-methoxy benzene sulfonamide derivatives 3 and 4 showed slight antitumour activity.

Primary tuberculous muscle abscess in a patient with systemic lupus erythematosus.

Infectious complications are a very common and prominent cause of both morbidity and mortality in patients with systemic lupus erythematosus. We present a patient who developed a paravertebral primary tuberculous muscle abscess after aggressive treatment with corticosteroids and immunosuppressive agents.

Synthesis and characterization of new methylpsoralens as potential photochemotherapeutic agents.

Three new psoralens with methyl groups on carbons involved in their reactive double bonds (compounds 9-11 in Scheme 1) were synthesized from the corresponding 7-hydroxycoumarins by cyclization of acetonyl derivatives of the latter in an alkaline medium. In preliminary tests, the new methyl-substituted psoralens exhibited considerable interaction in the dark with DNA, good photoreactivity against the macromolecule, and also interesting antiproliferative activity.

Synthesis and photobiological properties of 4-hydroxymethyl-4'-methylpsoralen derivatives.

The synthesis and the photobiological activity of two new hydroxymethyl derivatives of psoralen namely 4-hydroxymethyl-4'-methyl- and 4-hydroxymethyl-4'-methyl-8-methoxypsoralen are described. Both compounds exhibited efficient photobinding to DNA and RNA. The DNA-photobinding process was investigated using different nucleic acid structures such as double-helical DNA, ribosomal RNA, bacterial DNA and DNA organized in the nucleosomal arrangement.

Synthesis and photobiological activity of new methylpsoralen derivatives.

The synthesis and the photobiological activity of two new derivatives of psoralen (3,4'-dimethylpsoralen and 3,4',8-trimethylpsoralen) has been described. They are congeners of the monofunctional linear furocoumarin 3,4'-dimethyl-8-methoxypsoralen. Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8.