Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds.

INTRODUCTION: Over the past 5 years, we have witnessed intense research activity about the biological potential of natural products (NPs) as human monoamine oxidase B (hMAO-B) inhibitors. Despite the promising inhibitory activity, natural compounds often suffer from pharmacokinetic lissues, such as poor aqueous solubility, extensive metabolism, and low bioavailability. AREAS COVERED: This review provides an overview of the current landscape NPs as selective hMAO-B inhibitors and highlights their use as a starting scaffold to design (semi)synthetic derivatives to overcome the therapeutic (pharmacodynamic and pharmacokinetic) limitations of NPs and to obtain more robust structure-activity relationships (SARs) for each scaffold. EXPERT OPINION: All the natural scaffolds herein presented displayed a broad chemical diversity. The knowledge of their biological activity as inhibitors of hMAO-B enzyme allows the positive correlations associated with the consumption of specific food or the possible herb-drug interactions and suggests to the Medicinal Chemists how to address chemical functionalization to obtain more potent and selective compounds.

Antimicrobial and Antibiofilm Activities of Carvacrol, Amoxicillin and Salicylhydroxamic Acid Alone and in Combination vs. Helicobacter pylori: Towards a New Multi-Targeted Therapy.

The World Health Organization has indicated Helicobacter pylori as a high-priority pathogen whose infections urgently require an update of the antibacterial treatments pipeline. Recently, bacterial ureases and carbonic anhydrases (CAs) were found to represent valuable pharmacological targets to inhibit bacterial growth. Hence, we explored the underexploited possibility of developing a multiple-targeted anti-H. pylori therapy by assessing the antimicrobial and antibiofilm activities of a CA inhibitor, carvacrol (CAR), amoxicillin (AMX) and a urease inhibitor (SHA), alone and in combination. Minimal Inhibitory (MIC) and Minimal Bactericidal (MBC) Concentrations of their different combinations were evaluated by checkerboard assay and three different methods were employed to assess their capability to eradicate H. pylori biofilm. Through Transmission Electron Microscopy (TEM) analysis, the mechanism of action of the three compounds alone and together was determined. Interestingly, most combinations were found to strongly inhibit H. pylori growth, resulting in an additive FIC index for both CAR-AMX and CAR-SHA associations, while an indifferent value was recorded for the AMX-SHA association. Greater antimicrobial and antibiofilm efficacy of the combinations CAR-AMX, SHA-AMX and CAR-SHA against H. pylori were found with respect to the same compounds used alone, thereby representing an innovative and promising strategy to counteract H. pylori infections.