68592-19-8Relevant articles and documents
Synthesis and in vitro antitumor evaluation of honokiol derivatives
Zhu, Meilin,Li, Bohan,Ma, Hui,Huang, Xuenan,Wang, Haotian,Dai, Yiqun,Li, Yu,Li, Hong-Mei,Wu, Cheng-Zhu
supporting information, (2019/12/25)
Honokiol is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC50 value of 10.41 μM. Transwell assays showed that 5a could significantly inhibit the invasion and migration of I-10 cells at 2.5 μM, which was further confirmed by the western blotting experiments with down-regulation of the HIF-1α and its associated downstream proteins MMP-2 and MMP-9. Overall, these results provided useful suggestion for further structural optimization of honokiol derivatives.
Nitrogenated honokiol derivatives allosterically modulate GABAA receptors and act as strong partial agonists
Bernaskova, Marketa,Schoeffmann, Angela,Schuehly, Wolfgang,Hufner, Antje,Baburin, Igor,Hering, Steffen
, p. 6757 - 6762 (2015/10/20)
In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignan honokiol together with its isomer magnolol are the main constituents of Magnolia bark extracts. We have previously identified a nitrogen-containing honokiol derivative (3-acetylamino-4′-O-methylhonokiol, AMH) as a high efficient modulator of GABAA receptors. Here we further elucidate the structure-activity relation of a series of nitrogenated biphenyl-neolignan derivatives by analysing allosteric modulation and agonistic effects on α1β2γ2S GABAA receptors. The strongest IGABA enhancement was induced by compound 5 (3-acetamido-4′-ethoxy-3′,5-dipropylbiphenyl-2-ol, Emax: 123.4 ± 9.4% of IGABA-max) and 6 (5′-amino-2-ethoxy-3′,5-dipropylbiphenyl-4′-ol, Emax: 117.7 ± 13.5% of IGABA-max). Compound 5 displayed, however, a significantly higher potency (EC50 = 1.8 ± 1.1 μM) than compound 6 (EC50 = 20.4 ± 4.3 μM). Honokiol, AMH and four of the derivatives induced significant inward currents in the absence of GABA. Strong partial agonists were honokiol (inducing 78 ± 6% of IGABA-max), AMH (63 ± 6%), 5′-amino-2-O-methylhonokiol (1) (59 ± 1%) and 2-methoxy-5′-nitro-3′,5-dipropylbiphenyl-4′-ol (3) (52 ± 1%). 3-N-Acetylamino-4′-ethoxy-3′,5-dipropyl-biphenyl-4′-ol (5) and 3-amino-4′-ethoxy-3′,5-dipropyl-biphenyl-4′-ol (7) were less efficacious but even more potent (5: EC50 = 6.9 ± 1.0 μM; 7: EC50 = 33.2 ± 5.1 μM) than the full agonist GABA.
Efficient synthesis and structure-activity relationship of honokiol, a neurotrophic biphenyl-type neolignan
Esumi, Tomoyuki,Makado, Gouki,Zhai, Haifeng,Shimizu, Yasuhiro,Mitsumoto, Yasuhide,Fukuyama, Yoshiyasu
, p. 2621 - 2625 (2007/10/03)
Honokiol, a biphenyl-type neolignan, which shows the remarkable neurotrophic effect in primary cultured rat cortical neurons, has been effectively synthesized in 21% yield over 14 steps starting from 5-bromosalicylic acid and p-hydroxybenzoic acid by utilizing Pd-catalyzed Suzuki-Miyaura coupling reaction as a key step. Additionally, the structure-activity relationship between neurite outgrowth-promoting activity and its O-methylated and/or its hydrogenated analogues was examined in the primary cultures of fetal rat cortical neurons, suggesting that 5-allyl and 4′-hydroxyl groups are essential for affecting the neurotrophic activity of honokiol.