Cytotoxic Clerodane Diterpenes from Zuelania guidonia

Abstract

The leaves of Zuelania guidonia yielded eight new clerodane diterpenes, namely, zuelaguidins A-H (1-8), and the known clerodane diterpene esculentin A (9). Some of these structures contained a 3,6-dihydro-1,2-dioxin moiety. The new compounds were isolated and identified using 1D- and 2D-NMR experiments. All compounds were evaluated for cytotoxicity against the CCRF-CEM (human acute lymphocytic leukemia), CEM-ADR5000 (human acute lymphocytic leukemia resistant to doxorubicin), and MIA-PaCa-2 (human pancreatic carcinoma) cell lines as well as for their selectivity against peripheral blood mononuclear cells from healthy human subjects. Zuelaguidins B, C, and E were the most potent compounds against the CCRF-CEM cell line, with IC50 values ranging from 1.6 to 2.5 μM.

Clerodane diterpenes: sources, structures, and biological activities

“…The structures of zuelaguidins A–D ( 17–20 ) from Z. guidonia are typical of this subtype. 16 Corymbulosins A–C ( 25–27 ) from Laetia corymbulosa were elucidated as clerodane diterpenes unsaturated at C-3, C-13(16), and C-14. 18 Corymbulosin A ( 25 ) has a decadienoate ester at C-2, while corymbulosins B and C ( 26–27 ) have a saturated decanoate ester at C-6.…”

“…For example, esculentin A ( 76 ) has been reported in both ent–neo 16 and neo 32 configurations. In addition, while caseargrewiin A ( 74 ) was shown as a neo -clerodane, caseargrewiins B–D ( 1256–1258 , structures in Section 3.5) co-isolated from C. grewiifolia were shown as ent-neo -clerodanes.…”

“…This endoperoxide may result from a Diels–Alder reaction between zuelaguidin A ( 17 , see Section 2.1.1.1), also found in Z. guidonia , and molecular oxygen. 16 Compounds 153–155 are 5 : 10 cis and 17 : 20 trans . The remaining compounds in type I subtype Ic are 5 : 10 trans and 17 : 20 cis , as typical of clerodanes isolated from the family Asteraceae.…”

The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling

“…Casearin J (CJ; Figure 1a ) is a tricyclic clerodane diterpene found in Casearia sylvestris , a plant from the Salicaceae family. We have previously reported that representatives of this class of secondary plant metabolites are preferentially cytotoxic to leukemia cells 16 and that they directly inhibit the SERCA pump. 17 However, the exact mechanism of cytotoxicity and the reason for their preference toward leukemia cells remain poorly understood.…”

An Erratum

“…The leaves of Zuelania guidonia yielded clerodane DE called zuelaguidins E (92) and G (93). [106] Tigliane-type diterpenoid called crotusin C (94) was isolated from the methanolic extract of the twigs and leaves of Croton caudatus. [107] The data on the biological activity of DEs are given in table 4.…”