Why are there virtually no antibiotics in clinical use based on bioactive compounds from plants?

Infections are often treated with (medicinal) plants by traditional healers. Extracts from these (as well as many other) plants often exhibit antimicrobial activity in vitro. In fact, numerous bioactive compounds with antimicrobial activity have been isolated and identified from such extracts. However, very few of these compounds have been developed into clinically used antibiotics. This contrasts strongly with antimicrobial compounds from microorganisms.

Various reasons for this apparent paradox have been proposed. These include (1) insufficient potency of most antimicrobial natural products, (2) synergy required with other plant secondary metabolites for full efficacy, (3) insufficiently chemical or in vivo stability, (4) low oral bioavailability, (5) unfavorable pharmacokinetics, (6) toxicity or small therapeutic window, (7) narrow antimicrobial spectrum, (8) rapid development of resistance, (9) difficult to patent, (10) no economically viable production possible (by full synthesis, semi-synthesis, bioproduction, etc. ). In this talk, I will review and evaluate each of these, and draw some conclusions that may guide future research in this area.