Combination screening of synthetic drugs and plant derived natural products—Potential and challenges for drug development

SummaryPlants are a precious source for medicine and drug development. An estimated one third of our present medicines are derived from natural sources – either directly isolated, synthesized or semi-synthesized by structural modification of their natural compounds. Well known examples are colchicine, morphine, semi-synthetic aspirin, taxol or penicillin. However, drug development from natural sources as well as by synthesis is presently facing a set back. Most new drugs fail in the step from the preclinic to the clinic; equally a loss of activity is observed during the bioactivity screening of plant extracts for the identification of active single constituents. The source material has often a superior activity over the isolated single constituents which give reasons to doubt whether a single active principle is present. These developments are paralleled by deeper insights into the pathophysiology of chronic and/or severe diseases. They are usually multifactorial and require a multitarget treatment. Drug combinations have become routine in the treatment of cancer, HIV or cardiovascular diseases. The selected drug combinations are based on the known mode of actions of each single drug. Their combinations in vivo are mainly empirical. Systematic screening of combinations of already approved drugs has started only recently. The potential of combining phytomedicine or natural products with synthetic drugs or introducing these into conventional treatment regimes are not yet systematically explored. This review presents recent examples of combination screenings. The screening for synergetic effects of such combinations is technically demanding and complex, also in the context of drug–herb interactions, but likely to substantially advance pharmacotherapy and future medicine.