Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and benzofuroxan) were synthesized and characterized as potential antiplatelet/antithrombotic compounds. All compounds (3a,b, 4a,b, 8a,b, 9a,b, 13a,b and 14a,b) inhibited platelet aggregation induced by adenosine-5-diphosphate, collagen, and arachidonic acid. All compounds protected mice from pulmonary thromboembolism induced by a mixture of collagen and epinephrine; however, benzofuroxan derivatives (13a,b and 14a,b) were the most active compounds, reducing thromboembolic events by up to 80%. N-oxide derivative 14a did not induce genotoxicity in vivo. In conclusion, 14a has emerged as a new antiplatelet/antithrombotic prototype useful for the prevention of atherothrombotic events.
Tuberculosis is one of the leading causes of morbidity and mortality worldwide. Current treatment has several challenges, such as multi-drug resistance, extensively drug-resistance and HIV co-infection. Problems related to patients, treatment and health care system also contribute negatively to this panel. This review summarizes the main obstacles causing in the treatment of tuberculosis and discusses several strategies to improve the treatment.
Sickle cell disease (SCD) is one of the most common genetic disorders worldwide. It is caused by a point mutation that changes glutamic acid (Glu6) to valine (Val6) in the β chain of hemoglobin. Vaso-occlusion is the most well-known problem associated with SCD. Despite recent advances in understanding the disease at the molecular level, few therapeutic strategies are available. Hydroxyurea is the only drug currently approved by the U.S. Food and Drug Administration for the disease, and it has serious adverse effects and lack of efficacy in some patients. However, new therapeutic approaches are under investigation in the hope of discovering new drugs to treat SCD.These include agents that: a) increase nitric oxide bioavailability; b) modify the rheological properties of the blood; c) bind covalently to hemoglobin; d) prevent hemoglobin dehydration; e) reduce iron overload; and f) induce the expression of gamma globin and fetal hemoglobin. In this chapter, we discuss the current treatment of SCD and the advances made in medicinal chemistry to find new drugs to treat this neglected hematological disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.