Four diterpenes identified in silico were isolated from Hyptidinae and demonstrated in vitro activity against Mycobacterium tuberculosis

Abstract

Plants of Hyptidinae subtribe (Lamiaceae – family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis.

Graphical Abstract

Keywords:

• Hyptidinae
• diterpenes
• Mesosphaerum sidifolium
• in silico model
• Mycobacterium tuberculosis

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq), grant numbers 309648/2019-0, 431254/2018-4, and 404440/2016-9 and by the Coordination of Improvement of Higher Education Personnel – Brazil (CAPES) – Financing Code 001.