In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 ∼ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure–activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.

Parasitic and bacterial infections affecting the gastrointestinal tract represent a significant cause of morbidity and mortality worldwide. Nitroheterocyclic drugs have been available since the early 1960s for the treatment of anaerobic protozoa. The application of these drugs has widened and they are presently used to treat anaerobic pathogenic bacteria and protozoa. 5-nitroimidazoles are a well-established group of antiprotozoal and antibacterial agents that inhibit the growth of both anaerobic bacteria and certain anaerobic protozoa, such as Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia. The important antibacterial and antiprotozoal activities of nitroimidazoles are associated with reductive metabolism that has led to considerable interest in nitroimidazole reduction chemistry and the synthesis of new, highly effective drugs. The present review provides a brief account of various biological activities exhibited by synthetic nitroimidazole derivatives as well as their structure-mutagenicity relationships.

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Malaria is one of the most severe tropical parasitic disease causing 1-3 million deaths annually. In the last 25 years very few new antimalarial molecules have been developed and only a limited number of them are currently in various stages of clinical development. The presently available antimalarial drugs include artemisinin analogs, quinoline derivatives and antifolates. This review summarizes recent advances in antimalarial drug development and world patents published between 2000-2006 claiming new synthetic antimalarial compounds and their activities. The most over-represented classes of compounds in malaria patent literature in order of frequency are artemisinin analogs, quinoline derivatives, DOXP reductoisomerase inhibitors, antifolates and febrifugine analogues. Many of these patents describe the novelty and potential of these synthetic derivatives with an attempt to identify the next generation antimalarials that may have potential commercial advantages.

In the present study, a series of 1,4-naphthoquinone derivatives were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H 37 Rv strain by the broth microdilution assay method. The in vitro antitubercular activity data of the tested compounds against M. tuberculosis strain H 37 Rv showed moderate to good activity against bacteria compared to reference drugs. The most effective compounds of the series are 26, 28, 29, 34 and 36 with IC 50 values ranging from 3.9 -0.3 µg/mL. The objective of our study is to generate new leads that operate through a different mode of action and to optimize their structure to display potent efficacy.