Alkaloids as drug leads – A predictive structural and biodiversity-based analysis

The process of drug discovery and development particularly that of natural products, has evolved markedly over the last 30 years into increasingly formulaic approaches. As a major class of natural products initially discovered and used as early as 4000 years ago, alkaloids and the species they are derived from have been used worldwide as a source of remedies to treat a wide variety of illnesses. Yet, a tremendously wide discrepancy between their historical significance and their occurrence in modern drug development exists. Are alkaloids underrepresented in modern medicine? The physicochemical features of 27,683 alkaloids from the Dictionary of Natural Products were cross-referenced to pharmacologically significant and other metrics from various databases including the European Bioinformatics Institute's ChEMBL and Global Biodiversity Information Facility's GBIF. For the first time we show that market/developmental performance of a class of compounds is linked to its biodiversity distributions, as defined by the GBIF dataset. The potential of such a large-scale data analysis is analyzed against both prevalent rules used to guide drug discovery processes and the larger context of natural product development.