Diterpenoids from Roots of Salvia lachnocalyx; In-silico and In-vitro Toxicity against Human Cancer Cell Lines

Document Type: Research article

Authors

1 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Department of Molecular Physiology, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Abstract

Further investigations on phytochemical constituents of dichloromethane extract from
roots of Salvia lachnocalyx (S. lachnocalyx) led to the isolation and identification of eight
known diterpenoids from this plant for the first time. The chemical structures of the purified
compounds were elucidated using spectroscopic analyses including EI-MS, 1H and 13C NMR and
by comparison of the resulting spectra with those reported in the literature. Then, the cytotoxic
activity of identified compounds was examined against two human cancer cell lines MCF-7
(human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia). Molecular
docking of promising cytotoxic compounds were performed by AutoDock Tools 1.5.4 program
in the active site of Topoisomerase I. Eight known diterpenoids; 12-hydroxysapriparaquinone
(1), 15-deoxyfuerstione (2), horminon (3), 7α-acetoxyroyleanone (4), 11β-hydroxymanoyl
oxide (5), microstegiol (6), 1-keto-aethiopinone (7) and 14-deoxycoleon U (8) were isolated of
dichloromethane extract from roots of salvia lachnocalyx. Compounds 2, 3, 6, and 8 showed
cytotoxic activity against MCF-7 (human breast adenocarcinoma) and K562 (human chronic
myelogenous leukemia) cell lines with IC50 values in the range of 2.63-11.83 μg/mL. The inhibition
of” topoisomerase I” was suggested by molecular docking calculations as the mechanism of
cytotoxicity of the tested compounds. According to cytotoxic assay and docking results, it is
suggested that compounds 2, 3, 6, and 8 have good potential as anticancer agents.

Graphical Abstract

Diterpenoids from Roots of Salvia lachnocalyx; In-silico and In-vitro Toxicity against Human Cancer Cell Lines

Keywords