Synthesis of 1-O-acetylbritannilactone analogues from Inula britannica and in vitro evaluation of their anticancer potential

Abstract

A series of novel ABL analogues was synthesized by N/O-atom installing and aromatic ring esterifying, and 4a showed in vitro markedly anticancer activities against HeLa cells associated with induction of apoptosis, activation of caspase-3 and G2/M cell arrest.

Diversity Modification and Structure-Activity Relationships of Two Natural Products 1β-hydroxy Alantolactone and Ivangustin as Potent Cytotoxic Agents

“…Their esterified derivatives 1a – h and 2a – c containing introduction of aliphatic chain (acetyl and carboxypropionyl) or aromatic groups (benzoyl and cinnamoyl) at C1-OH position exhibited weaker cytotoxic activity than 1 and 2 against these cancer cell lines. It is different from previous reports about another STLs 1- O -acetylbritannilactone (ABL) 18 , 19 by us and others 31 , 32 , where ABL esterified derivatives have shown stronger suppression against cancer cells than ABL. These results indicated that C1-OH is important for activity in the two natural molecules 1 and 2 .…”

“…Since the α-methylene-γ-lactone moiety in the STLs skeleton is one of major active sites, modifications of this moiety were being conducted 18 , 30 , 36 . It was reported that natural products bearing spirobicyclic moiety usually exhibited high biological activity 17 , 37 – 40 , such as inducing autophagy activity by clionamine D 40 .…”

Exploring Diverse-Ring Analogues on Combretastatin A4 (CA-4) Olefin as Microtubule-Targeting Agents

“…The apoptosis in HepG2 cells was detected with a propidium iodide (PI)/Annexin V-FITC apoptosis detection kit (KeyGEN Biotech, Nanjing, China) as described previously [42]. After the treatment of 6b-(Z), 6b-(E) and CA-4 at the indicated concentrations for 48 h, HepG-2 cells were stained with PI and Annexin V-FITC and then were resuspended in 400 µL of binding buffer.…”

(S)-4-[(3aR,4S,7aR)-4-Methoxy-6-methyl-3-methylene-2-oxo-2,3,3a,4,7,7a-hexahydrobenzofuran-5-yl]pentyl Acetate

“…Therefore, structure modifications for improving ABL bioactivity at both positions of ABL have been conducted by many medicinal chemists. Structural modifications of ABL have focused mainly on alterations at 6-OH moiety such as oxidation and acylation by Liu [12][13][14] and us [11,15]. However, etherified ABL analogues have not been synthesized so far, perhaps due to the complexity of its structure (sensitive to strong acid or base) and larger steric hindrance.…”