Development of a rapid and reliable assay for in vitro determination of compound cidality against the asexual stages of Plasmodium falciparum.

The pace of anti-malarial drug discovery is often impeded due to the lack of tools to determine the cidality of compounds in vitro. An anti-malarial compound must have a cidal mode of action, i.e.

Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.

The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (TAPs), which emerged from a phenotypic screen against the blood stages of Pf. The clinical candidate (compound 12) is efficacious in a mouse model of Pf malaria with an ED99 <30 mg kg(-1) and displays good in vivo safety margins in guinea pigs and rats.

Prevalence of risk factors for coronary artery disease in an urban Indian population.

Objective: The objective of this study was to assess the prevalence of risk factors for coronary artery disease (CAD) in government employees across India.

Methods: The study population consisted of government employees in different parts of India ({n=10,642 men and n=1966 women; age 20-60 years}) and comprised various ethnic groups living in different environmental conditions. Recruitment was carried out in 20 cities across 14 states, and in one union territory.

N-aryl-2-aminobenzimidazoles: novel, efficacious, antimalarial lead compounds.

From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P.