Neglected Aspects of Drug Discovery - Microbiological Aspects

Jacob      Golenser; Nicholas      Hunt

doi:10.2174/1574884711308010010

Abstract

Developing new, efficient drugs is a long and costly process. However, although a failure to establish new drugs can in part be related to lack of funding, often it is also associated with various deficiencies in current approaches to drug development. Chemical and genetic validation, in addition to estimating future drug resistance, are considered critical for predicting the therapeutic efficacy of a compound. However, such approaches, when employed to decide upon further investigation or rejection of a candidate drug, often ignore several factors. These are: (i) the possibility of successful treatment by rejected drugs – compounds used in the past that individually are no longer effective because of resistance but are useful in combination; (ii) synergy between drugs that are not necessarily directed against the pathogen; (iii) drugs that can attenuate immune or inflammatory responses and consequently can alleviate clinical symptoms that are caused by host responses against the pathogen. High-throughput screening (HTS) could be adapted to accommodate these categories but, ultimately, only in vivo assessment would reveal really significant therapeutic effects. One group of investigators is unlikely to be able to complete the development of a drug, from idea to a successful product. However, individual efforts might contribute and be significant for the advance towards drug applicability.

Keywords: Drug combinations, drug resistance, high-throughput screening, infectious diseases, pathogens, drug development, Aspergillus fumigatus, Leishmania donovani, pharmacokinetics and pharmacodynamics, submicromolar concentrations