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.
Synthesis of Either C2- or C4′-Alkylated Derivatives of Honokiol and Their Biological Evaluation for Anti-inflammatory Activity
Lee, San-Ha,Fei, Xiang,Lee, Chaelin,Do, Hien Thi Thu,Rhee, Inmoo,Seo, Seung-Yong
, p. 966 - 976 (2019/09/07)
Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4′-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4′-alkylated derivative.
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.
Structural modification of honokiol, a biphenyl occurring in magnolia officinalis: The evaluation of honokiol analogues as inhibitors of angiogenesis and for their cytotoxicity and structure-activity relationship
Ma, Liang,Chen, Jinying,Wang, Xuewei,Liang, Xiaolin,Luo, Youfu,Zhu, Wei,Wang, Tianen,Peng, Ming,Li, Shucai,Jie, Shi,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
experimental part, p. 6469 - 6481 (2011/12/01)
Honokiol, widely known as an antitumor agent, has been used as an antiangiogenesis drug lead. In this paper, 47 honokiol analogues and derivatives were investigated for their antiangiogenic activity by application of the transgenic zebrafish screening model, antiproliferative and cytotoxic activity against HUVECs, and three tumor cell lines by MTT assay. 3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde (8c) was found to suppress the newly grown segmental vessels from the dorsal aorta of zebrafish and prevent inappropriate vascularization as well as exhibit more potent inhibitory effects on the proliferation of HUVECs, A549, HepG2, and LL/2 cells (IC50 = 15.1, 30.2, 10.7, and 21.7 μM, respectively) than honokiol (IC50 = 52.6, 35.0, 16.5, and 65.4 μM, respectively). Analogue 8c also effectively inhibited the migration and capillary-like tube formation of HUVECs in vitro. The antiangiogenic effect and antiproliferative activity of these structurally modified honokiol analogues and derivatives have led to the establishment of a structure-activity relationship.
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.
NEUROTROPHIC SESQUITERPENE-NEOLIGNANS FROM MAGNOLIA OBOVATA: STRUCTURE AND NEUROTROPHIC ACTIVITY
Fukuyama, Yoshiyasu,Otoshi, Yukio,Miyoshi, Kumi,Nakamura, Kazuhiko,Kodama, Mitsuaki,et al.
, p. 377 - 392 (2007/10/02)
Novel sesquiterpene-neolignans, eudesobovatols A (1) and B (2), eudesmagnolol (3), eudeshonokiols A (4) and B (5), clovanemagnolol (6), and caryolanemagnolol (7), have been isolated from the bark of Magnolia obovata.Their structures were elucidated to be sesquiterpenes (eudesmol, 4,4,8-trimethyltricyclo2,5>dodecane-1,9-diol, and clovanediol) combined through ether bond with neolignans such as obovatol, honokiol, and magnolol on the basis of spectral data, degradation, and/or synthesis.Compounds 1, 6, and 7 were found to exhibit interesting neurotrophic activity on a neuronal cell culture system derived from fetal rat hemisphere.
Structures of Eudesmagnolol and Eudeshonokiol, Novel Sesquiterpene-Neolignans Isolated from Magnolia obovata
Fukuyama, Yoshiyasu,Otoshi, Yukio,Nakamura, Kazuhiko,Kodama, Mitsuaki,Sugawara, Michiharu,Nagaswa, Masakazu
, p. 295 - 296 (2007/10/02)
Eudesmagnolol and eudeshonokiol, isolated from the bark of Magnolia obovata, have been assigned to unprecedented structures linked via an ether bond between sesquiterpene, eudesmol, and neolignans, magnolol and honokiol, respectively.
