Design and Optimization of Quinazoline Derivatives: New Non-nucleoside Inhibitors of Bovine Viral Diarrhea Virus.

Bovine viral diarrhea virus (BVDV) belongs to the genus (). In spite of the availability of vaccines, the virus is still causing substantial financial losses to the livestock industry. In this context, the use of antiviral agents could be an alternative strategy to control and reduce viral infections.

Identification of potent bovine viral diarrhea virus inhibitors by a structure-based virtual screening approach.

Bovine viral diarrhea virus (BVDV) is a pestivirus whose infection in cattle is globally distributed. The use of antivirals could complement vaccination as a tool of control and reduce economic losses. The RNA-dependent RNA polymerase (RdRp) of the virus is essential for its genome replication and constitutes an attractive target for the identification of antivirals.

Synthesis, 2D-QSAR Studies and Biological Evaluation of Quinazoline Derivatives as Potent Anti-Trypanosoma cruzi Agents.

Background: Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease.

Thalidomide analogues: Tumor necrosis factor-alpha inhibitors and their evaluation as anti-inflammatory agents.

A series of related thalidomide derivatives (2-9) were synthesized by microwave irradiation and evaluated for anti-inflammatory activity. Such activity was assessed in vivo and ex vivo. Compounds 2, 8 and 9 showed the highest levels of inhibition of TNF-α production.

Trypanocidal activity of thioamide-substituted imidazoquinolinone: electrochemical properties and biological effects.

Three thioamide-substituted imidazoquinolinone, which possess a heterocyclic center similar to tryptanthrin and are named C1, C2, and C3, were studied regarding (a) their in vitro anti-Trypanosoma cruzi activity, (b) their cytotoxicity and electrochemical behaviour, and (c) their effect on cell viability, redox state, and mitochondrial function. The assayed compounds showed a significant activity against the proliferative forms, but only C1 showed activity on the trypomastigote form (for C1, IC50  epi = 1.49 μM; IC50  amas = 1.

Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation.

Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia.

New potent imidazoisoquinolinone derivatives as anti-Trypanosoma cruzi agents: biological evaluation and structure-activity relationships.

A series of novel benzoimidazo and N-aryl-5-oxo-imidazo[1,2-b]isoquinoline-10-carbothioamides was developed. All the compounds were evaluated for their in vitro action against the epimastigote form of Trypanosoma cruzi. Four of them showed higher activity than Nifurtimox.

Design, synthesis, and antitumor activity of new bis-aminomethylnaphthalenes.

A new series of bis-aminomethylnaphthalenes were synthesized in satisfactory overall yield, through a simple synthetic strategy using reductive amination. The DNA binding properties of these compounds have been examined and compared to those of reference drugs using an UV spectroscopy method. The compounds were evaluated for their in vitro anticancer activity and some of them were studied in vivo.

Design, synthesis, and biological evaluation of alcyopterosin A and illudalane derivatives as anticancer agents.

The synthesis of alcyopterosin A and a series of new derivatives possessing an illudalane skeleton is described. The DNA binding properties of these compounds have been examined and compared to those of reference drugs using a UV spectroscopy technique. The antitumor activity of selected compounds against a panel of 60 human tumor cell lines was tested in the in vitro anticancer screening of the National Cancer Institute.

1, 2, 4-Triazine N-oxide derivatives: studies as potential hypoxic cytotoxins. Part III.

New 5-(2-arylethenyl)-1, 2, 4-triazine N-oxide and N, N'-dioxide derivatives were synthesized in order to obtain compounds as selective hypoxic cell cytotoxins. The desired products were obtained when the 5-methyl heterocycle reacted with the corresponding iminium electrophiles. The new compounds were tested for their cytotoxicity in oxia and hypoxia.

Benzothiadiazine dioxide human cytomegalovirus inhibitors: synthesis and antiviral evaluation of main heterocycle modified derivatives.

The benzothiadiazine dioxide derivatives are potent non-nucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship (SAR) study of these compounds, we have now proposed structural modifications on the heterocyclic moiety both on the number and the nature of the fused heterocycle and on the kind of heteroatoms present on it. Synthesis of these new compounds (benzyl derivatives of thiadiazines, thienothiadiazines, benzothienothiadiazines and quinazolines) and the antiviral evaluation against HCMV has been performed.