193551-50-7Relevant academic research and scientific papers
Fascaplysin Derivatives Are Potent Multitarget Agents against Alzheimer's Disease: In Vitro and in Vivo Evidence
Pan, Hanbo,Qiu, Hongda,Zhang, Ke,Zhang, Panpan,Liang, Weida,Yang, Mengxiang,Mou, Chenye,Lin, Miaoman,He, Ming,Xiao, Xiao,Zhang, Difan,Wang, Haixing,Liu, Fufeng,Li, Yongmei,Jin, Haixiao,Yan, Xiaojun,Liang, Hongze,Cui, Wei
, p. 4741 - 4756 (2019)
Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a β-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and β-amyloid (Aβ) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Aβ oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Aβ-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment.
Fascaplysin derivatives binding to DNA via unique cationic five-ring coplanar backbone showed potent antimicrobial/antibiofilm activity against MRSA in vitro and in vivo
Cui, Wei,Liang, Hongze,Liang, Weida,Lin, Jiayu,Qiu, Hongda,Tan, Xinyi,Teng, Da,Wang, Jianhua,Wang, Ning,Wang, Xiao,Xie, Haoji,Yang, Na,Zhou, Jiale,Zhou, Yuan,Zhu, Haifeng
, (2022/01/11)
Methicillin-resistant Staphylococcus aureus (MRSA) is considered as one of the most dangerous clinical pathogens. Biofilms forming ability of MRSA is also a major cause of drug resistance. Hence, it is in urgent need to develop novel antibacterial/antibiofilm drugs. Fascaplysin with a unique cationic five-ring coplanar backbone is emerging as a potential antibacterial compound. In this study, aiming at developing novel and more effective agents, a series of fascaplysin derivatives and their corresponding β-carboline precursors have been synthesized. Then their antibacterial/antibiofilm activity and mechanisms against MRSA were investigated for the first time. The results showed that most fascaplysins rather than β-carboline precursors exhibit superior antimicrobial activity against MRSA ATCC43300, demonstrating the important role of cationic five-ring coplanar backbone playing in antibacterial activity. Among them, 14 and 18 are the most potent compounds with MIC value of 0.098 μg/ml (10-fold lower than vancomycin), and 18 featuring the lowest toxicity. Subsequent mechanisms exploration indicates that 18 has relatively stronger ability to destroy bacterial cell wall and membrane, higher binding affinity to bacterial genomic DNA. Molecular docking study revealed that besides the key role of cationic five-ring coplanar backbone, introduction of N-aryl amide at 9-position of fascaplysin promoted the combination of compound 18 and DNA via additional π-π stacking and hydrogen bonding of the naphthyl group. Moreover, fascaplysins could inhibit MRSA biofilm formation in vitro and bacterial infection in vivo. All these results illustrate that fascaplysin derivative 18 is a strong and safe multi-target antibacterial agent, which makes it an attractive candidate for the treatment of MRSA and its biofilm infections.
Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship
Manda, Sudhakar,Sharma, Sadhana,Wani, Abubakar,Joshi, Prashant,Kumar, Vikas,Guru, Santosh K.,Bharate, Sonali S.,Bhushan, Shashi,Vishwakarma, Ram A.,Kumar, Ajay,Bharate, Sandip B.
, p. 1 - 11 (2015/11/17)
The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, rese
A cascade coupling strategy for one-pot total synthesis of β-carboline and isoquinoline-containing natural products and derivatives
Zhu, Yan-Ping,Liu, Mei-Cai,Cai, Qun,Jia, Feng-Cheng,Wu, An-Xin
supporting information, p. 10132 - 10137 (2013/09/02)
Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of β-carbolines. The method can direct the synthesis of β-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme). Copyright
Phosphane-free Pd0-catalyzed cycloamination and carbonylation with Pd(OAc)2 and Cu(OAc)2 in the presence of K 2CO3: Preparation of benzocyclic amines and benzolactams
Harada, Rika,Nishida, Naoto,Uchiito, Shiho,Onozaki, Yu,Kurono, Nobuhito,Senboku, Hisanori,Masao, Tokuda,Ohkuma, Takeshi,Orito, Kazuhiko
, p. 366 - 379 (2012/02/04)
Phosphane-free Pd0-catalyzed intramolecular aromatic amination was studied. o-Halophenethylamines and 3-(o-halophenyl)propylamines were found to be transformed into indolines and quinolines in a catalytic system based on Pd(OAc)2 and Cu(OAc)2 in the presence of K 2CO3. Application of the method to substrates containing isoquinoline rings- the 1-(o-bromobenzyl)-3,4-dihydroisoquinolines 6, the 1-(o-bromobenzyl)-1,2,3,4-tetrahydroisoquinolines 7, and the 1-(o-bromophenethyl)isoquinolines 9- provided the indolo[2,1-a]isoquinoline and dibenzo[a,f]quinolizine ring systems 8 and 10. Extension of the method to β-carbolines (compounds 11, 12, and 17) produced the benz[f]indolo[2,3-a] indolizine-13-ones 15 and the benz[f]indolo[2,3-a]quinolizine 18. The benzo[f]pyrido[3,4-a]indolizine and indolo[f]pyrido[3,4-a]indolizin-12-one ring systems 27 and 31 were built in a similar manner. It was also found that under an atmosphere of CO the same catalytic system produced the corresponding benzolactams, the isoquino[2,1-a][2,7]naphthyridine 34 and the indolo[2,3-a]pyrido[g]quinolizin-8-one 36 [(±)-dihydronauclefine] in good yields. Copyright
Synthesis, in vitro anti-inflammatory and cytotoxic evaluation, and mechanism of action studies of 1-benzoyl-β-carboline and 1-benzoyl-3-carboxy-β-carboline derivatives
Yang, Mei-Lin,Kuo, Ping-Chung,Hwang, Tsong-Long,Chiou, Wen-Fei,Qian, Keduo,Lai, Chin-Yu,Lee, Kuo-Hsiung,Wu, Tian-Shung
experimental part, p. 1674 - 1682 (2011/04/16)
In the present study, various 1-substituted and 1,3-disubstituted β-carboline derivatives were synthesized by a modified single-step Pictet-Spengler reaction. The compounds were examined for cytotoxicity and anti-inflammatory activity, as measured by the
Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-β-carbolines
Garcia, Marcos D.,Wilson, A. James,Emmerson, Daniel P. G.,Jenkins, Paul R.
, p. 2586 - 2588 (2008/03/31)
The synthesis of a series of β-carboline-based analogues of the natural product fascaplysin is presented; the compounds were produced using a novel photo-oxidation reaction of 1-benzyl-4,9-dihydro-3H-β-carbolines as the key step. The Royal Society of Chemistry 2006.
Synthesis, crystal structure and biological activity of β-carboline based selective CDK4-cyclin D1 inhibitors
Garcia, Marcos D.,Wilson, A. James,Emmerson, Daniel P.G.,Jenkins, Paul R.,Mahale, Sachin,Chaudhuri, Bhabatosh
, p. 4478 - 4484 (2008/09/19)
The design, synthesis and biological activity of a series of non-planar dihydro-β-carboline and β-carboline-based derivatives of the toxic anticancer agent fascaplysin is presented. We show these compounds to be selective inhibitors of CDK4 over CDK2 with an IC50 (CDK4-cyclin D1) = 11 mol for the best compound in the series 4d. The crystallographic analysis of some of the compounds synthesised (3b/d and 4a-d) was carried out, in an effort to estimate the structural similarities between the designed inhibitors and the model compound fascaplysin. The Royal Society of Chemistry.
A simple and practical approach to the synthesis of the marine sponge pigment fascaplysin and related compounds
Radchenko, Oleg S.,Novikov, Vyacheslav L.,Elyakov, George B.
, p. 5339 - 5342 (2007/10/03)
Fascaplysin 1, an antimicrobial and cytotoxic red pigment of the marine sponge Fascaphysinopsis sp., has been synthesized in five steps from tryptamine 2 in 44% overall yield. The key steps in the synthesis are: (a) dehydrogenation of the dihydro-β-carboline intermediate 4 simultaneously with its benzylic oxidation on treatment with MnO2 and (b) the thermal cyclization of the resulting β-carboline 7 into a quaternary salt 8. Similarly, indoloisoquinolines 15 and 16, the tetracyclic analogues of 1, were prepared in six steps from α-amino ketone 9 in 59 and 55% overall yields, respectively.
