Cytotoxic Guaianolide Sesquiterpenoids from Ainsliaea fragrans

Abstract

Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of Ainsliaea fragrans, including a novel trimer (1) and two new dimers (2, 3). The chemical structures of the new compounds were elucidated through spectroscopic data interpretation and computational calculations. Ainsfragolide ( 1) is an unusual guaianolide sesquiterpene trimer generated with a novel C−C linkage at C 2' −C 15″ , which may be biosynthesized prospectively through a further Michael addition. Cytotoxicity results showed that ainsfragolide (1) was the most potent compound against five cancer cell lines with IC 50 values in the range of 0.4−8.3 μM.

Structurally Diverse Sesquiterpenoids from the Genus of Ainsliaea

“…[46,53] Among them, ainsliatriolide B (170) contains a rare spiro-ketal functionality possibly formed as shown in Scheme 4. Ainsfragolide and macrocephatriolide A were reported from two different species at almost same time, [14,47] but they indeed share the same structure (171). Macrocephatriolide B (172) from A. macrocephala might be derived from a Michael addition reaction of dehydrozaluzanin C (38) and ainsliadimer J (160), two cooccurring sesquiterpenoids.…”

“…[46] However, the same trivial name was also used to name structurally different disesquiterpenoid from A. fragrans. [47] To distinguish them, the one from A. fragrans [47] was renamed as gochnatiolide E' (150) in this review. Ainsliadimer D was firstly reported from A. macrocephala along with ainsliadimer C (153), [24] later its structure was revised as ainsliadimer B (152).…”

“…A large number of Ainsliaea sesquiterpenoids have been screened for cytotoxic effects, and some sesquiterpenoids, especially those bearing an α,β-unsaturated ketone moiety, exerted promising anti-proliferative activities against a panel of cancer cells. [13,38,46,47,51,53] The underlying reason may be that α,βunsaturated ketone can spontaneously react with thiols in protein by nucleophilic addition to produce certain cytotoxicity. [57,58] For example, mononeric sesquiterpenoids, zaluzanin C (34) and alantolactone (120), exhibited significant and non-specific inhibition against several cancer cell lines.…”

Huoshanmycins A‒C, New Polyketide Dimers Produced by Endophytic Streptomyces sp. HS-3-L-1 From Dendrobium huoshanense

“…Since the discovery of taxol and taxane produced by an endophytic fungus from the phloem (inner bark) of Pacific yew in 1993 ( Stierle et al, 1993 ), endophytes have become an important resource in the field of bioactive natural products discovery ( Newman and Cragg, 2015 ; Gómez and Luiz, 2018 ), as they can produce analogs or bioactivity-related compounds as their hosts did ( Cui et al, 2012 ; Zhao et al, 2020c ). As part of an effort to characterize novel natural products from medicinal plants ( Wang et al, 2009 ; Ding et al, 2021 ; Hu et al, 2021 ) and their endophytes ( Zhao et al, 2020b ; Zhao et al, 2020a ; Zhu et al, 2021 ), herein we report the isolation and characterization of three new polyketide dimers from an endophyte Streptomyces sp. HS-3-L-1 of the D. huoshanense leaf.…”

Biomimetic Synthesis of Lavandiolides H, I, and K and Artematrolide F via Diels–Alder Reaction

“…Dimethylaminomicheliolide and thapsigargin prodrug G-202 are undergoing clinical trials for the treatment of cancers. , Oligomeric guaianolides make up a unique group of terpenoids biogenetically assembled by at least two monomeric guaianolide units via diverse biosynthesis pathways. To date, hundreds of dimeric guaianolides, seven trimeric guaianolides, and two tetrameric guaianolides have been isolated from natural sources.…”