Novel 2-arylazoimidazole derivatives as inhibitors of Trypanosoma cruzi proliferation: Synthesis and evaluation of their biological activity.

In this work, the synthesis of a series of 2-arylazoimidazole derivatives 6-20 has been achieved through the reaction of imidazole with aryldiazonium salts, followed by ultrasound-assisted alkylation. This approach has important advantages including higher yield, shorter reaction times and milder reaction conditions. The structures of the compounds obtained were determined by MS, IR; and H and C NMR.

Bis-naphthylureas and related compounds: synthesis, chemical properties, DNA affinity and antineoplastic activity.

A series of bis-naphthalene derivatives in which these moieties are linked by a symmetric bis-urea functionalized chain or by an asymmetric amide and urea or amino and urea functionalized chain, were synthesized. The tentative synthesis of other types of related compounds did not give the products expected. The compounds were assayed as antineoplastics on human tumor cell lines at the National Cancer Institute (USA).

Human DNA topoisomerase I poisoning activity of bis-1-aminomethylnaphtalenes. A correlation with their cytotoxic activity.

Symmetrical bis-1-aminmoethylnaphtalenes, a group of compounds that demonstrated cytotoxicity towards human tumor cell lines, showed human topoisomerase I poisoning activity. The compounds tested were: N,N'-bis-1-naphthylmethyl-1,6-hexanediamine (1a), N,N'-bis-1-naphthylmethyl-1,8-octanediamine (1b), N,N'-bis-1-naphthylmethyl-1,12-dodecanediamine (1c), N,N'-bis-1-naphthylmethyl-4,4-bipiperidine (2) and N-(1-naphthylmethyl)-N'-dimethyl-1,3-diaminepropane dichlorhydrate (3). All showed human topoisomerase I inhibition by producing protein-linked DNA breaks.

Diarylsemicarbazones: synthesis, antineoplastic activity and topoisomerase I inhibition assay.

A series of diarylsemicarbazones was synthesized and tested against human neoplastic cell lines. The more active members have a l-naphthyl ring at the carbamidic nitrogen, and chloro, dimethylamino or nitro group substituents at the benzylidene moiety. None of these showed affinity to DNA.

DNA interaction and electrochemical properties of bis-1-aminomethylnaphthalenes and related compounds. A correlation with their antineoplastic activity.

Bis-1-aminomethylnaphthalenes constitute a new type of molecule with antineoplastic activity. As a first approach to determine the action mechanism, the interaction degree of these compounds and some less active analogous, with calf thymus DNA, by UV spectrophotometry, and the redox performance by cyclic voltammetry was correlated with their activity on neoplastic cell lines. It suggests that the most active members interact closely with DNA but do not show any redox process at biological potentials.

Synthesis, DNA interaction and antineoplastic activity of semicarbazone derivatives.

A number of antineoplastic agents including procarbazine and bisantrene derive from hydrazine, but so far none have been developed from semicarbazide. In order to assay active minimal structures, thirteen new compounds were prepared by replacing hydrogen atoms in semicarbazone amine group by alkylamine moieties, employing an improved procedure. DNA binding was evaluated by treatment of a drug solution with DNA-cellulose complex and further measurement of remaining drug by UV spectroscopy and the affinity observed to range from medium to weak.