6543-34-6Relevant articles and documents
A synthetic approach to kingianin A based on biosynthetic speculation
Sharma, Pallavi,Ritson, Dougal J.,Burnley, James,Moses, John E.
, p. 10605 - 10607 (2011)
A synthetic approach towards the structurally complex dimer, kingianin A is reported. The strategy involved a cascade of complexity generating reactions, inspired through biosynthetic speculation. A concise protecting group free synthesis of the proposed monomeric precursor pre-kingianin A has been achieved using a tandem Stille cross-coupling reaction and electrocyclisation process. However, preliminary studies of the key dimerisation reaction have been conducted, which indicate that the process is not spontaneous, raising questions as to the origin of this complex natural product.
Structural elucidation, bio-inspired synthesis, and biological activities of cyclic diarylpropanes from Horsfieldia kingii
Chen, Lei,Chen, Ye-Gao,Li, Dashan,Liu, Yuan-Lie,Shao, Li-Dong,Wang, Wen-Jing,Xie, Xiao-Yan,Zhan, Rui
, (2020/09/02)
Bioactivity-guided phytochemical investigation on 70% aqueous acetone extracts of the twigs and leaves of Horsfieldia kingii led to the isolation of two novel cyclic diarylpropanes (1 and 2) bearing a 2,3-dihydro-1H-indene core, one new diarylpropane (3), six known diarylpropanes (4–9), one flavanol (10), and seven lignans (11–17). Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculations, and X-ray diffraction crystallography. Moreover, a biomimetic synthesis of 1 and 2 were accomplished in four steps. The in vitro nitric oxide production inhibition tests of these compounds revealed that compounds (±)-2, (+)-2, (?)-2, and 10 were potential with IC50 values lower than 10 μM. Compound 2 could inhibit iNOS expression in LPS-induced RAW264.7 cells at a series of non-cytotoxic concentrations (20 μM). Furthermore, the bioassay results also suggested the primary SARs of 1-phenyl-2,3-dihydro-1H-indene based scaffold.
Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy
An, Hongchan,Lee, Seungbeom,Lee, Jung Min,Jo, Dong Hyun,Kim, Joohwan,Jeong, Yoo-Seong,Heo, Mi Jeong,Cho, Chang Sik,Choi, Hoon,Seo, Ji Hae,Hwang, Seyeon,Lim, Jihye,Kim, Taewoo,Jun, Hyoung Oh,Sim, Jaehoon,Lim, Changjin,Hur, Joonseong,Ahn, Jungmin,Kim, Hyun Su,Seo, Seung-Yong,Na, Younghwa,Kim, Seok-Ho,Lee, Jeewoo,Lee, Jeeyeon,Chung, Suk-Jae,Kim, Young-Myeong,Kim, Kyu-Won,Kim, Sang Geon,Kim, Jeong Hun,Suh, Young-Ger
, p. 9266 - 9286 (2018/10/24)
Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1α, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1α inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1α inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-1α inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1α inhibitors that can be used in lieu of a chromene ring.
