The screening strategy is essentially a numbers game. Given structural diversity, the more compounds screened the better the chance of finding biological activity and generating a lead area. The limitation of this approach is that the synthesis of novel chemicals is labour intensive and relatively slow. This also requires the preparation of a large number of compounds and indeed it is not possible to synthesise all of the possible analogs of a given, promising lead by traditional methods. Combinatorial chemistry attempts to address this limitation by adopting an alternative to the traditional chemistry paradigm of producing a single, well-characterised product.
Combinatorial chemistry employs two alternative strategies.
One is to simultaneously create a plethora of compounds and screen the mixture for activity. The active component, if one exists, is then identified and prepared by standard methodology. In principal, a greater number of compounds can be quickly prepared and screened in this way. The attraction of the combinatorial approach is the speed and cost effectiveness of generating molecular diversity - the challenge is to develop methods to readily identify the active component in a complex mixture either through labelling or statistical methods. Crucial to this effort is a basic understanding of the biochemical pathways of a target organism.