Xeronine structure and function: computational comparative mastery of its mystery

Abstract

Morinda citrifolia (Noni) fruit has a long history of dietary use in tropical regions of the world. Pharmacological properties that have been attributed to the fruit include anti-inflammatory, anti-cancer, and antioxidant properties. Xeronine, a small alkaloid which has been patented (US4543212) is one of the bioactive compounds of Noni fruit, which is believed to be capable of modifying the molecular structure of specific inactive proteins thereby regulating proper folding to active enzymes. Despite reports of the potential of Xeronine as therapeutic agent, its presence is controversial and its structure has not been explored. In this study, standard chemoinformatics tools and servers such as ChemSketch, ChemMine, Swisstargetprediction, SwissADME and Swisssimilarity have been employed to predict its possible structure. In addition, synthetic xeronine structures based on the known bioactive components of Noni fruit were designed. Results showed that the hypothetical structure of xeronine provided by the patent inventor is a mystery based on its <5% probable protein targets and no similarity match to the US Food and Drug Administration (FDA) approved drugs and experimental compounds by in silico evaluation. By constrast, final designed xeronine structure possess all the features that were described in the patent document, and has >40% probable protein targets related to neurodegenerative diseases such as Alzheimer's disease (AD), which possibly justifies the key function stated in the patent.

Keywords: Cheminformatics; De novo drug design; Morinda citrifolia; Noni fruit; Xeronine.

Fig. 1

Hypothetical structure of xeronine

Fig. 2

a Xeronine structure C1. b Xeronine structure C2

Fig. 3

MDS clustering with correlation (similarity cutoff 0.5, dimensions 2D)

Fig. 4

Designed structure of synthetic xeronine