22848-79-9

Usage

Uses

Used in Pharmaceutical Research:
(4beta,5beta,6beta,22S)-1,26-dioxo-5,6:22,26-diepoxyergosta-2,24-diene-4,27-diyl diacetate is used as a research compound for exploring its biological activities and potential therapeutic effects. Its unique structure allows scientists to investigate its interactions with various biological targets and pathways.
Used as a Precursor in Synthesis:
In the pharmaceutical industry, (4beta,5beta,6beta,22S)-1,26-dioxo-5,6:22,26-diepoxyergosta-2,24-diene-4,27-diyl diacetate serves as a valuable precursor for the synthesis of other bioactive compounds. Its versatile structure can be modified to create new molecules with potential medicinal properties.
Used in Organic Chemistry:
(4beta,5beta,6beta,22S)-1,26-dioxo-5,6:22,26-diepoxyergosta-2,24-diene-4,27-diyl diacetate is utilized in organic chemistry to study the reactions and transformations of complex steroidal structures. This helps chemists develop new synthetic methods and understand the reactivity of similar compounds.

Upstream product

• 108-24-7 acetic anhydride 
• 5119-48-2 withaferin-A 

Relevant academic research and scientific papers

Structure-based design, synthesis, and biological evaluation of withaferin A-analogues as potent apoptotic inducers

Apoptosis inducers represent an attractive approach for the discovery and development of anticancer agents. Herein, we report on the development by molecular fine tuning of a withaferin A-based library of 63 compounds (2–64), 53 of them reported for the first time. Their antiproliferative evaluation on HeLa, A-549 and MCF-7 human tumor cell lines identified fifteen analogues displaying higher activity (IC50 values ranging 0.3–4.8 μM) than the lead (IC50 values ranging 1.3–10.1 μM) either in lag or log growth phases. SAR analysis revealed that acylation enhances cytotoxicity, suggesting the hydrophobic moiety contributes to the activity, presumably by increasing affinity and/or cell membrane permeability. Further investigation clearly indicated that compounds 3, 11, 12, and 18 induce apoptosis evidenced by chromatin condensation, phosphatidylserine externalization, and caspase-3 activation effects on HeLa cells. The potent capacity to induce apoptosis with concomitant cell loss in G2/M highlights the potential of 27-benzyl analogue (18) as an apoptotic inducer drug candidate.

Structure-activity relationships for withanolides as inducers of the cellular heat-shock response

To understand the relationship between the structure and the remarkably diverse bioactivities reported for withanolides, we obtained withaferin A (WA; 1) and 36 analogues (2-37) and compared their cytotoxicity to cytoprotective heat-shock-inducing activity (HSA). By analyzing structure-activity relationships for the series, we found that the ring A enone is essential for both bioactivities. Acetylation of 27-OH of 4-epi-WA (28) to 33 enhanced both activities, whereas introduction of β-OH to WA at C-12 (29) and C-15 (30) decreased both activities. Introduction of β-OAc to 4,27-diacetyl-WA (16) at C-15 (37) decreased HSA without affecting cytotoxicity, but at C-12 (36), it had minimal effect. Importantly, acetylation of 27-OH, yielding 15 from 1, 16 from 14, and 35 from 34, enhanced HSA without increasing cytotoxicity. Our findings demonstrate that the withanolide scaffold can be modified to enhance HSA selectively, thereby assisting development of natural product-inspired drugs to combat protein aggregation-associated diseases by stimulating cellular defense mechanisms.