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Two new cis-clerodane-type furanoditerpenes, crispenes F and G (1 and 2), together with seven known compounds, were isolated from the stems of Tinospora crispa. Crispenes F and G (1 and 2) inhibited STAT3 dimerization in a cell-free fluorescent polarization assay and were found to have significant cytotoxicity against a STAT3-dependent MDA-MB 231 breast cancer cell line, while being inactive in a STAT3-null A4 cell line. These two compounds share structural similarities with a previously reported STAT3 inhibitor, crispene E, isolated from the same plant. Molecular docking studies suggested that the molecules inhibit STAT3 by interacting with its SH2 domain.

Crispenes F and G, cis-Clerodane Furanoditerpenoids from Tinospora crispa, Inhibit STAT3 Dimerization