Preferred, Novel and Neglected Scaffolds: Natural Products in a Drug Discovery Program

Over the past few years, Sequoia Sciences has identified preferred, neglected, and novel drug-like scaffolds from its extensively purified library of plant compounds. Some of these scaffolds have more chiral centers and non-aromatic rings than synthetically inspired compounds. Since the majority of known scaffolds have been neglected in drug discovery [1] can neglected and novel plant scaffolds inspire the drugs of 2020? Certain representative scaffolds will be presented and compared to known drugs and published synthetic scaffolds that have undergone lead optimization.

Payne [2] stated „Right now, there are no novel mechanism-of-action antibacterials in Phase I, nor are there even good preclinical leads with promising Gram-negative activity.“ Is this an accurate assessment of antibacterial discovery programs foretelling more doom in the hospitals? If so, can antibacterial therapeutics that improve the effectiveness of existing antibiotics satisfy demand until 2030? Sequoia will present data demonstrating a plant-inspired compound that increases the effectiveness of gram-negative antibiotics. The story starts from a plant and evolves to a semisynthetically produced novel scaffold that inhibits the expansion of gram-negative biofilms and potentiates the activities of antibiotics.

References: [1] Lipkus, A.H. et al. (2008)J. Org. Chem. 73:4443–4451.

[2] Payne, D.J. et al. (2007) in Nat. Rev. Drug Discov. 6:29–40.