Fifty years of chemical research at Farmitalia.

This review contains a brief description of the chemistry developed in Farmitalia and, after 1978, Farmitalia-Carlo Erba Research Laboratories, during the second half of the last century. It gives an overview of work that represents a significant part of the chemistry carried out in Italy during this period in the field of medicinal and natural product chemistry. This is particularly true when we consider in addition to the work done intramurally in the said laboratories, the work done by academic scientists in the frame of the various extramural collaborations.

In vitro antiviral activity of distamycin A against clinical isolates of herpes simplex virus 1 and 2 from transplanted patients.

Objective(s): Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs.

Sabarubicin.

Disaccharide derivatives in the daunorubicin and in the 4-demethoxy (idarubicin) series in whichthe first sugar moiety linked to the aglycone is a non-aminated sugar, namely 2-deoxy-L-rhamnose or 2-deoxy-L-fucose andthe second moiety is daunosamine, have been obtained upon synthesis of the appropriate activated sugarintermediate and glycosylation of the corresponding aglycones. The compounds containing 2-deoxy-L-fucose exhibit superior pharmacological properties with respect to thestereoisomers containing 2-deoxy-L-rhamnose. The doxorubicinanalog 7-O-(α-L-daunosaminyl-α(1-4)-2-deoxy-L-fucosyl)-4-demethoxy-adriamycinone (sabarubicin) was prepared startingfrom 14-acetoxyidarubicinone.

Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells.

Covalent attachment of intercalating agents to triplex-forming oligonucleotides (TFOs) is a promising strategy to enhance triplex stability and biological activity. We have explored the possibility to use the anticancer drug daunomycin as triplex stabilizing agent. Daunomycin-conjugated TFOs (dauno-TFOs) bind with high affinity and maintain the sequence-specificity required for targeting individual genes in the human genome.

Improved synthesis of daunomycin conjugates with triplex-forming oligonucleotides. The polypurine tract of HIV-1 as a target.

Triple helix-forming oligonucleotides (TFOs) are promising agents for the control of gene expression, as they can selectively bind to a chosen oligopyrimidine.oligopurine region of a gene of interest thus interfering with its expression. The stability of the triplex formed by the TFO and the duplex is often too poor for successful applications of TFOs in vivo and the conjugation of a DNA intercalating moiety to the TFO is a common way to enhance the TFO affinity for its target.