36455-21-7Relevant articles and documents
Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D
Zheng, Liuliu,Gao, Tingting,Ge, Zhiwei,Ma, Zhongjun,Xu, Jinzhong,Ding, Wanjing,Shen, Li
, (2021)
Lamellarin D, a marine natural product, acts as a potent inhibitor of DNA topoisomerase I (Topo I). To modify its physicochemical property and biological activity, a series of mono- and di-glycosylated derivatives were designed and synthesized through 22–26 multi-steps. Their inhibition of human Topo I was evaluated, and most of the glycosylated derivatives exhibited high potency in inhibiting Topo I activity as well as lamellarin D. All the 15 target compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The typical lamellarin derivative ZL?3 exhibited the best activity with IC50 values of 3 nM, 10 nM, and 15 nM against human lung cancer A549 cells, human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells. Compound ZL?1 exhibited anti-cancer activity with IC50 of 14 nM and 24 nM against human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells, respectively. Cell cycle analysis in MDA-MB-231 suggested ZL?3 inhibited cell growth through arresting cells at the G2/M phase of the cell cycle. Further tests showed a significant improvement in aqueous solubility of ZL?1 and ZL?7. This study suggested that glycosylation could be utilized as a useful strategy to optimize lamellarin D derivatives as Topo I inhibitors and anticancer agents.
An Expeditious Modular Hybrid Strategy for the Diversity-Oriented Synthesis of Lamellarins/Azalamellarins with Anticancer Cytotoxicity
Klumthong, Kanawut,Chalermsub, Papornchanok,Sopha, Pattarawut,Ruchirawat, Somsak,Ploypradith, Poonsakdi
, p. 14883 - 14902 (2021/09/13)
A modular hybrid strategy has been developed for the diversity-oriented synthesis of lamellarins/azalamellarins. The common pentacyclic pyrrolodihydroisoquinoline lactone/lactam core was formed via the Michael addition/ring closure (Mi-RC) and the copper(I) thiophene-2-carboxylate (CuTC)-catalyzed C-O/C-N Ullmann coupling. Subsequent direct functionalization at C1, DDQ-mediated C5C6 oxidation, and global deprotection of all benzyl-type O- and N-protecting groups furnished the desired lamellarins/azalamellarins. The late-stage functionalization at C1 provided a handle to accommodate a wider scope of functional groups as they need to tolerate only the DDQ oxidation and global deprotection. Moreover, with the C1-H pyrrole as the late-stage common intermediate, it was also possible to divergently exploit not only its nucleophilic nature to react with some electrophilic species but also some transition-metal-catalyzed cross-coupling reactions (via the intermediacy of the C1-iodopyrrole) to incorporate diversity at this position. Overall, this strategy simplifies the preparation of lamellarins/azalamellarins; including the Mi-RC, these C1-structurally diverse analogues could be prepared efficiently in 6-7 steps from the easily accessed 1-acetoxymethyldihydroisoquinoline and β-nitrocinnamate. Some selected azalamellarins were evaluated for their inhibitory effect against HeLa cervical cancer cells. An acute induction of intrinsic apoptosis was detected and may lead to growth suppression of or cytotoxicity against cancer cells.
The synthesis of precursor of FP- (+) DTBZ
Wu, Caijiao,Li, Hui,Sun, Feiyang,Bao, Changshun,Bao, Xuefei,Chen, Guoliang
, p. 3218 - 3225 (2019/09/13)
A synthetic route to the precursor of FP- (+) DTBZ was disclosed, in which 3-hydroxy-4-methoxybenzaldehyde was employed as a starting material. In the method, the benzyl-protecting protocol and the in-situ Diels-Alder reaction made the procedure more practical because of the mild conditions for selectively deprotection and the accelerated reaction process.
Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors
Lee, David Y.W.,Liu, Jing,Zhang, Shuzhen,Huang, Peng,Liu-Chen, Lee-Yuan
, p. 1437 - 1440 (2017/03/08)
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. L-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites L-ICP, L-CD, and L-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
Colligs, Vanessa,Hansen, Steven Peter,Imbri, Dennis,Seo, Ean-Jeong,Kadioglu, Onat,Efferth, Thomas,Opatz, Till
, p. 6137 - 6148 (2017/09/30)
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
NOVEL ANTHRANILIC ACID DERIVATIVES
-
Paragraph 000118, (2016/07/20)
The present invention is directed to a novel compound of Formula 1 wherein the radiolabeled compound of Formula 1 is capable of being used as a radiotracer in PET imaging of a targeted localized tissue and targeted radionuclide therapy of one or more conditions that may be regulated or normalized via inhibition of transporter such as Pgp, BCRP or MRP I. The novel compounds of Formula 1 can also be used as substrates for binding with one or more ABC transporters. In particular, the present invention aids in diagnosis and therapeutic treatment of MDR disorders in all forms of cancers and neurological disorders of the central nervous system. The present invention further provides methods of preparation of compounds of Formula 1 and novel intermediates used in the preparation of compounds of Formula 1.
ANTI-HIV COMPOUNDS
-
Paragraph 0305, (2016/07/05)
This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.
PHENANTHRENE DERIVATIVES FOR USE AS MEDICAMENTS
-
Page/Page column 0056; 0057; 0058, (2016/08/07)
The present invention refers to phenanthrene derivatives for use as medicaments, mainly in the prevention and/or treatment of Myotonic Dystrophy Type 1, Huntington's Disease Like 2, Spinocerebellar Ataxia Type 8, Myotonic Dystrophy Type 2, Spinocerebellar Ataxia Type 3, Fragile-X-Associated Tremor/Ataxia Syndrome, Frontotemporal Degeneration/Amyotrophic Lateral Sclerosis and Spinocerebellar Ataxia Type 31. In a preferred embodiment, phenanthrene derivatives of the invention are also used as antimyotonic agents. Therefore, this invention may be included either in the whole pharmaceutical or medical field.
Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
, p. 925 - 937 (2015/03/31)
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
Facile and Divergent Synthesis of Lamellarins and Lactam-Containing Derivatives with Improved Drug Likeness and Biological Activities
Theppawong, Atiruj,Ploypradith, Poonsakdi,Chuawong, Pitak,Ruchirawat, Somsak,Chittchang, Montakarn
, p. 2631 - 2650 (2016/02/09)
With the goal to improve the aqueous solubility of lamellarins, the lactone ring in their skeleton was replaced with a lactam moiety in azalamellarins. However, the reported synthetic route produced such derivatives in very low yields. Hence, this study focused on developing an efficient simplified total synthetic scheme that could furnish both azalamellarins and the parent lamellarins from the same pyrrole ester intermediates. Subsequent comparative profiling revealed that the introduced lactone-to-lactam replacement rendered these molecules less lipophilic, whereas their cancer cytotoxicity remained equipotent to that of the parent compounds. Interestingly, their inhibitory activity was significantly enhanced towards the multifaceted GSK-3β enzyme. Our results clearly demonstrate the therapeutic potential of this promising class of marine-derived natural products and justify their further development, especially into anticancer agents.
