Cytotoxic and alpha amylase-inhibitory metabolites from Tagetes minuta: In vitro evaluation and docking studies

Abstract

Purpose: To investigate the cytotoxic and alpha-amylase inhibitory (AAI) potential of methanol (MeOH) extract of T. minuta and its isolated metabolites. 
 Methods: Phytochemical investigation of MeOH extract of the aerial parts of T. minuta was accomplished using SiO2 and Rp-18 column chromatography (CC). The structures of the isolated metabolites were determined and verified based on various data, in addition to comparison with literature data. The metabolites were assessed for cytotoxic potential against HepG2, MCF-7, and HCT116 cell lines utilizing sulphur rhodamine B (SRB) assay. The in vitro AAI potential of the metabolites were also assayed, and the findings were confirmed using results from molecular docking studies. 
 Results: One thiophene (compound 1), one coumarin (compound 2), and three phenolic compounds (compounds 3-5) were isolated and characterized. Compound 1 exhibited a marked cytotoxic effect (IC50 values: 2.7 – 7.3 μM) on HepG2, MCF-7, and HCT116 cell lines, relative to doxorubicin (IC50 values: 0.18 - 0.60 μM), whereas compound 2 had a moderate cytotoxic effect on MCF-7 (IC50 17.7 μM). Besides, compounds 4 and 5 produced potent AAI effects, with IC50 values of 12.3 and 9.2 μM, respectively, and 91.8 and 94.7 % inhibition, respectively), when compared to acarbose (94.7 % inhibition and IC50 of 7.1 μM). Interestingly, the in vitro AAI and in silico results were in agreement with each other. Compounds 5 and 4 had more negative docking scores (-13.655 and -12.135 kcal/mol, respectively) than the native inhibitors, myricetin (-12.155 kcal/mol) and acarbose (-15.105 kcal/mol). 
 Conclusion: These results suggest that T. minuta is a valuable source of anti-diabetic and cytotoxic metabolites. However, there is a need to validate these results through additional in vivo and in vitro investigations.