Chemical and biological studies on sesterterpenes from Salvia dominica

Plants belonging to the genus Salvia show high diversity in their secondary metabolites as well as in pharmacological effects [1], and several species of Salvia are included in many pharmacopeias. Twenty species of Salvia grow wildly in Jordan, a country dominated by arid climate but with high biodiversity. As a part of our project on the study of plants belonging to the Jordanian flora, we performed phytochemical investigations of S. dominica [2]. Twenty new sesterterpenes were isolated from the apolar extract of aereal parts of the plant, and underwent a complete structural characterization by NMR, mass spectrometry and chemical approaches. Moreover, preliminary tests on the biological activity indicated that the apolar extract of aereal parts of S. dominica posses moderate antiproliferative activity. On the basis of these evidences, we developed an activity based proteomic approach [3] to identifiy protein(s) in human cancers cell able to interact with our compounds, whose inactivation could be responsible for the observed biological activity. This strategy allowed us to individuate Tubulin Tyrosine Ligase 1 (TTL1), a protein involved in microtubule formation during the cell division process [4], as a specific target of S. dominica sesterterpens. Besides, evaluating the thermodynamic and kinetic parameters of their interaction with (TTL1) by Surface Plasmon Resonance [5], a structure-activity relationship analysis was performed on all the isolated compounds, leading to the identification of the structural features playing a key role in the interaction.