We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2...We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.展开更多
Tricyclic and tetracyclic terpanes are important constituents of crude oil and source rock extracts.However,they have not been reported in the Offshore Niger Delta Basin,Nigeria.Thus,the present study investigated the...Tricyclic and tetracyclic terpanes are important constituents of crude oil and source rock extracts.However,they have not been reported in the Offshore Niger Delta Basin,Nigeria.Thus,the present study investigated the geochemical significance of tricyclic and tetracyclic terpanes in source rock extracts from the Offshore Niger Delta Bain,Nigeria with gas chromatography-mass spectrometry(GC-MS).The total relative abundances of tricyclic terpanes,C_(19)TT-C_(21)TT,and C_(23) TT in the rock samples ranged from 82.50 to 96.37%,50.08 to 74.17%,and 25.83 to 49.92%,respectively.These values showed the source rocks were formed from a mixed origin(terrestrial and marine).Among the tricyclic and tetracyclic terpanes identified in the rock extracts,the conventional(C_(20)TT,C_(23)TT,C_(24)TT,C_(24)TeT)and recent(Y1,X1,Z1)were more prominent than all others,indicating mixed input of terrigenous and marine organic matter.The C_(24)TT/C_(23)TT,C_(24)TeT/(C_(24)TeT+C_(26)TT),C_(19)TT/C_(23)TT,C_(20)TT/C_(23)TT,C_(25)TT/C_(24)TeT,C_(25)TT/C_(26)TT,C_(19)TT/C_(20)TT,C_(24)TeT/C_(26)TT,Z1/(Z1+C_(24)TT),and Y1/(Y1+C_(24)TT)in the rock samples range from 0.33 to 1.30,0.76 to 0.90,0.18 to 0.73,0.34 to 1.05,0.33 to 1.74,0.30 to 1.39,0.31 to0.89,1.66 to 4.33,0.36 to 0.83,and 0.34 to 0.79,respectively.These values further showed that the rock samples were formed from mixed input of terrigenous and marine organic matter and deposited under oxic to suboxic conditions in lacustrine-fluvial/deltaic environments.Also,the C_(24)TeT/C_(20)-26TT,C_(24)TeT/C_(30)HOP,and C_(23)TT/C_(30)HOP ranged from 0.16 to 0.45,0.02 to 0.42,and 0.01 to 0.48,respectively.This range of values suggests that source rocks were within immature to early mature stage.Thus,this study showed that tricyclic and tetracyclic terpanes were effective in determining the origin,depositional environments,and thermal maturity of source rocks in the Niger Delta Basin,Nigeria.展开更多
The tricyclic compound 1, a key intermediate of the pentacyclic core of Et 743 and its analogues, was synthesized. Its 11-epimer was found as the product of racemization when BOP was used as the coupling agent, but no...The tricyclic compound 1, a key intermediate of the pentacyclic core of Et 743 and its analogues, was synthesized. Its 11-epimer was found as the product of racemization when BOP was used as the coupling agent, but not when BOP-C1 used in the same reaction. The stereochemistry of both isomers was confirmed on basis of the 1H NMR and NOE-difference spectra.展开更多
Novel ethyl 7-chloro-6-fluoro-l-methyl-4-oxo-1, 4-dihydro-[1, 3]thiazeto[3, 2-a]quino- line-3-carboxylate 2 was prepared from 3-chloro-4-fluoroaniline in eight steps. It can be used as a new intermediate for the synth...Novel ethyl 7-chloro-6-fluoro-l-methyl-4-oxo-1, 4-dihydro-[1, 3]thiazeto[3, 2-a]quino- line-3-carboxylate 2 was prepared from 3-chloro-4-fluoroaniline in eight steps. It can be used as a new intermediate for the synthesis of tricyclic fluoroquinolones.展开更多
Tricyclic compounds (4b-endo) and (4b-exo) are synthesized as the plausible intermediates of the total synhthesis of hainanolide by Lewis acid catalyzed intramolecular DielsAlder (IMDA) reaction.
The tricyclic compoun d (2) C20H28O6 has been synthesized through thereaction of IMDA. The crystals of the title compound(2A) were crystallized from etherin monoclinic space group C2 with a unit cell: a = 11. 301 (2),...The tricyclic compoun d (2) C20H28O6 has been synthesized through thereaction of IMDA. The crystals of the title compound(2A) were crystallized from etherin monoclinic space group C2 with a unit cell: a = 11. 301 (2), b=11-.863 (3 ), c =29. 59 (1) , β= 101. 02(5)°, V=3894. 246, Dc=1.2413 g/cm3, Z=8, F(000)=1568, Mr= 364. 00 R=0.055, R2=0. 055, μ= 535 cm-1, S(GOF) =0. 571. Theconfiguration of C2a-H in the title compound was found to be contrary to what wasexpected and a possible mechanism of reaction was proposed.展开更多
An unexpected compound, hydroperoxide (4) formed from (3), the exo-cycloaddition product, which was synthesized through the Lewis acid catlyzed intramolecular Diels-Alder (IMDA) reaction. Its structure was confirmed b...An unexpected compound, hydroperoxide (4) formed from (3), the exo-cycloaddition product, which was synthesized through the Lewis acid catlyzed intramolecular Diels-Alder (IMDA) reaction. Its structure was confirmed by spectra and X-Ray diffraction analysis, An 1O2oxidation mechanism was proposed.展开更多
Let G be a graph and A=(aij)n×n be the adjacency matrix of G, the eigenvalues of A are said to be the eigenvalues of the graph G, and to form the spectrum of this graph. The numbers of positive, negative and zero...Let G be a graph and A=(aij)n×n be the adjacency matrix of G, the eigenvalues of A are said to be the eigenvalues of the graph G, and to form the spectrum of this graph. The numbers of positive, negative and zero eigenvalues in the spectrum of the graph G are called positive and negative inertia indexes and nullity of the graph G, are denoted by p(G), n(G), η(G), respectively, and are collectively called inertia indexes of the graph G. The inertia indexes have many important applications in chemistry and mathematics. The purpose of the research of this paper is to calculate the inertia indexes of one special kind of tricyclic graphs. A new calculation method of the inertia indexes of this tricyclic graphs with large vertices is given, and the inertia indexes of this tricyclic graphs with fewer vertices can be calculated by Matlab.展开更多
Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sourc...Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and Clinicaltrials.gov.Method:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional studies.Results:The literature search yielded 23 results,which were screened by three independent reviewers.Seventeen studies and three duplicates were excluded.An examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately included.Four studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment baseline.Three studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or TCAs.One study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment baseline.Conclusions:Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome reporting.There remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common MD symptoms.展开更多
Photo-induced electron transfer (PET) of silyl enol ethers has been employed to synthesize several fused ring systems. However, the method has limited applicability due to its narrow substrate scope, low product yield...Photo-induced electron transfer (PET) of silyl enol ethers has been employed to synthesize several fused ring systems. However, the method has limited applicability due to its narrow substrate scope, low product yields, unsatisfactory stereo- and regioselectivity. Herein, we report a PET-triggered cascade reaction of silyl enolates that leads to the formation of angularly fused tricyclic scaffolds. The reaction exhibits broad substrate scope and excellent stereoselectivity. The regio- and stereoselectivity of this cascade reaction is elucidated via DFT calculation and conformational analysis.展开更多
We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane(1)was a potent anti-diabetic agent.Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose c...We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane(1)was a potent anti-diabetic agent.Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose consumption in L6 myotubes,taking 1 as the lead.In high-fat diet(HFD)and STZ induced diabetic mice,9a significantly lowers blood glucose,improves glucose tolerance,and especially alleviates diabetic nephropathy and islet damage.Mechanism study indicates that 9a simultaneously targets mitochondrial complex I to increase AMP/ATP ratio,as well as liver kinase B1(LKB1)and calcium/calmodulindependent protein kinase(Ca MKK),which synergistically activates AMPKαand then stimulates glucose transporter 4(GLUT4)membrane translocation and 2-deoxyglucose(2-DG)uptake to exert anti-diabetic efficacy.Therefore,compound 9a with a novel structure is a promising anti-diabetic candidate with the advantage of multiple-target mechanism,worthy of further investigation.展开更多
The stereoselective syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reactio...The stereoselective syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reaction of chiral tricyclic iminolactone and aldehyde.展开更多
Natural products and their derivatives repre- sent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have bee...Natural products and their derivatives repre- sent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have been shown to be effective agents in the clinic or in preclinical settings. In the present review, we present a story of discovery, synthesis and evaluation of three synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs as cancer therapeutic agents. Chemical synthesis of these compounds (BA-TPQ, TBA-TPQ, and TCBA-TPQ) has been accomplished and the mechanisms of action (MOA) and structure-activity relationships (SAR) have been investigated. In the past, the complexity of chemical synthesis and the lack of well-defined MOA have dampened the enthusiasm for the development of some makaluvamines. Recent discovery of novel molecular targets for these alkaloids (unrelated to inhibition of Topoisomerase II) warrant further consideration as clinical candidates in the future. In addition to the establishment of novel synthetic approaches and demonstration of in vitro and in vivo anticancer activities, we have successfully demonstrated that these makaluvamines attack several key molecular targets, including the MDM2-p53 pathway, providing ample opportunities of modulating the compound structure based on SAR and the use of such compounds in combination therapy in the future.展开更多
One monoaromatic tricyclic diterpane and two aromatic tricyclic diterpanes were found in three low-maturity source rocks and five crude oils of the Tertiary Shahejie Formation in Shengli Oil Field. The compounds found...One monoaromatic tricyclic diterpane and two aromatic tricyclic diterpanes were found in three low-maturity source rocks and five crude oils of the Tertiary Shahejie Formation in Shengli Oil Field. The compounds found include C19H28 (m/z 145, M+ 256) ring-C monoaromatic tricyclic terpane, C17H20 (m/z 209, M+ 224) and C18H22 (m/z 223,M+ 238) rings-B,C diaromatic diterpanes. The results show that these compounds are biomarkers of immature organic matter with a stability sequence of C18H22 】 C17H20 】 C19H28. The cleavage of ring-D of pentacyclic triterpanoids, such as oleanene, hopene, fernene, ursene, in the early stage of diagenesis may be one of the origin pathways of rings-B, C diaromatic tricyclic diterpanes.展开更多
One-electron oxidation of N-4-desmethylwyosine (dYt), a derivative of rare tricyclic nucleoside wyosine with several oxidative radicals, has been studied by using pulse radiolysis. The transient spectra of the radical...One-electron oxidation of N-4-desmethylwyosine (dYt), a derivative of rare tricyclic nucleoside wyosine with several oxidative radicals, has been studied by using pulse radiolysis. The transient spectra of the radicals dYt˙+ and dYt(-H)˙ and the pK a of the radical cation were measured. The rate constants of reactions of dYt with SO 4 ˙? and CO 3 ˙? radicals have been determined and related reaction mechanisms were discussed.展开更多
Efficient synthetic routs for the direct and rapid construction of[5-6-6]ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully developed.For the daphmanidin A-type,the ...Efficient synthetic routs for the direct and rapid construction of[5-6-6]ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully developed.For the daphmanidin A-type,the synthesis of[5-6-6]tricyclic framework utilize a HCl-mediated intramolecular Aldol reaction to construct the bicyclo[2.2.2]octane core and a thermal condensation to afford the ABC ring system.In addition,for the calyciphylline A-type,an improved synthesis of ABC[5-6-6]tricyclic system was developed,featuring an introduction of methyl ester group at C2 before the Pd-catalyzed intramolecular oxidative alkylation to construct the desired bowl-shape tricyclic core with stereochemical control.展开更多
The synthesis of the ACE tricyclic system of daphnicyclidin A and dehydroxymacropodumine A are developed.The key reactions include an efficient aldol reaction to introduce chiral fragment 33 for further construction o...The synthesis of the ACE tricyclic system of daphnicyclidin A and dehydroxymacropodumine A are developed.The key reactions include an efficient aldol reaction to introduce chiral fragment 33 for further construction of piperidine ring B and seven-membered ring C, a nucleophilic addition of lithium pentene to aldehyde for installation of ring E,and a photocatalytic decarboxylation conjugate addition to construct ring C.展开更多
Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in viv...Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues re- ported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.展开更多
The spectral moments are the important algebraic invariants of graphs.In this paper,on the basis of definitions of tricyclic graphs,base and the sequence of spectral moments,respectively,we study tricyclic graphs with...The spectral moments are the important algebraic invariants of graphs.In this paper,on the basis of definitions of tricyclic graphs,base and the sequence of spectral moments,respectively,we study tricyclic graphs with given bases on the lexicographical order of the spectral moments sequence,and find the last and the first graphs.The results is very helpful for studying all tricyclic graphs ordering by spectral moments.展开更多
基金Supported by National Science Foundation, Tehran
文摘We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.
文摘Tricyclic and tetracyclic terpanes are important constituents of crude oil and source rock extracts.However,they have not been reported in the Offshore Niger Delta Basin,Nigeria.Thus,the present study investigated the geochemical significance of tricyclic and tetracyclic terpanes in source rock extracts from the Offshore Niger Delta Bain,Nigeria with gas chromatography-mass spectrometry(GC-MS).The total relative abundances of tricyclic terpanes,C_(19)TT-C_(21)TT,and C_(23) TT in the rock samples ranged from 82.50 to 96.37%,50.08 to 74.17%,and 25.83 to 49.92%,respectively.These values showed the source rocks were formed from a mixed origin(terrestrial and marine).Among the tricyclic and tetracyclic terpanes identified in the rock extracts,the conventional(C_(20)TT,C_(23)TT,C_(24)TT,C_(24)TeT)and recent(Y1,X1,Z1)were more prominent than all others,indicating mixed input of terrigenous and marine organic matter.The C_(24)TT/C_(23)TT,C_(24)TeT/(C_(24)TeT+C_(26)TT),C_(19)TT/C_(23)TT,C_(20)TT/C_(23)TT,C_(25)TT/C_(24)TeT,C_(25)TT/C_(26)TT,C_(19)TT/C_(20)TT,C_(24)TeT/C_(26)TT,Z1/(Z1+C_(24)TT),and Y1/(Y1+C_(24)TT)in the rock samples range from 0.33 to 1.30,0.76 to 0.90,0.18 to 0.73,0.34 to 1.05,0.33 to 1.74,0.30 to 1.39,0.31 to0.89,1.66 to 4.33,0.36 to 0.83,and 0.34 to 0.79,respectively.These values further showed that the rock samples were formed from mixed input of terrigenous and marine organic matter and deposited under oxic to suboxic conditions in lacustrine-fluvial/deltaic environments.Also,the C_(24)TeT/C_(20)-26TT,C_(24)TeT/C_(30)HOP,and C_(23)TT/C_(30)HOP ranged from 0.16 to 0.45,0.02 to 0.42,and 0.01 to 0.48,respectively.This range of values suggests that source rocks were within immature to early mature stage.Thus,this study showed that tricyclic and tetracyclic terpanes were effective in determining the origin,depositional environments,and thermal maturity of source rocks in the Niger Delta Basin,Nigeria.
文摘The tricyclic compound 1, a key intermediate of the pentacyclic core of Et 743 and its analogues, was synthesized. Its 11-epimer was found as the product of racemization when BOP was used as the coupling agent, but not when BOP-C1 used in the same reaction. The stereochemistry of both isomers was confirmed on basis of the 1H NMR and NOE-difference spectra.
基金we are grateful to the National Natural Science Foundation of China(No.20372043)for flnancial support for this Work.
文摘Novel ethyl 7-chloro-6-fluoro-l-methyl-4-oxo-1, 4-dihydro-[1, 3]thiazeto[3, 2-a]quino- line-3-carboxylate 2 was prepared from 3-chloro-4-fluoroaniline in eight steps. It can be used as a new intermediate for the synthesis of tricyclic fluoroquinolones.
文摘Tricyclic compounds (4b-endo) and (4b-exo) are synthesized as the plausible intermediates of the total synhthesis of hainanolide by Lewis acid catalyzed intramolecular DielsAlder (IMDA) reaction.
文摘The tricyclic compoun d (2) C20H28O6 has been synthesized through thereaction of IMDA. The crystals of the title compound(2A) were crystallized from etherin monoclinic space group C2 with a unit cell: a = 11. 301 (2), b=11-.863 (3 ), c =29. 59 (1) , β= 101. 02(5)°, V=3894. 246, Dc=1.2413 g/cm3, Z=8, F(000)=1568, Mr= 364. 00 R=0.055, R2=0. 055, μ= 535 cm-1, S(GOF) =0. 571. Theconfiguration of C2a-H in the title compound was found to be contrary to what wasexpected and a possible mechanism of reaction was proposed.
文摘An unexpected compound, hydroperoxide (4) formed from (3), the exo-cycloaddition product, which was synthesized through the Lewis acid catlyzed intramolecular Diels-Alder (IMDA) reaction. Its structure was confirmed by spectra and X-Ray diffraction analysis, An 1O2oxidation mechanism was proposed.
文摘Let G be a graph and A=(aij)n×n be the adjacency matrix of G, the eigenvalues of A are said to be the eigenvalues of the graph G, and to form the spectrum of this graph. The numbers of positive, negative and zero eigenvalues in the spectrum of the graph G are called positive and negative inertia indexes and nullity of the graph G, are denoted by p(G), n(G), η(G), respectively, and are collectively called inertia indexes of the graph G. The inertia indexes have many important applications in chemistry and mathematics. The purpose of the research of this paper is to calculate the inertia indexes of one special kind of tricyclic graphs. A new calculation method of the inertia indexes of this tricyclic graphs with large vertices is given, and the inertia indexes of this tricyclic graphs with fewer vertices can be calculated by Matlab.
文摘Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and Clinicaltrials.gov.Method:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional studies.Results:The literature search yielded 23 results,which were screened by three independent reviewers.Seventeen studies and three duplicates were excluded.An examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately included.Four studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment baseline.Three studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or TCAs.One study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment baseline.Conclusions:Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome reporting.There remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common MD symptoms.
基金supported by NSFC(21925106,U19A2014)Si-chuan University(2020SCUNL204)Department of Science and Technology of Sichuan Province(2023NSFSC0105).
文摘Photo-induced electron transfer (PET) of silyl enol ethers has been employed to synthesize several fused ring systems. However, the method has limited applicability due to its narrow substrate scope, low product yields, unsatisfactory stereo- and regioselectivity. Herein, we report a PET-triggered cascade reaction of silyl enolates that leads to the formation of angularly fused tricyclic scaffolds. The reaction exhibits broad substrate scope and excellent stereoselectivity. The regio- and stereoselectivity of this cascade reaction is elucidated via DFT calculation and conformational analysis.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-12M-1-030)the Natural Science Foundation of Beijing Municipality(No.7202131)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(No.GL-1-B04-20190397)。
文摘We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane(1)was a potent anti-diabetic agent.Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose consumption in L6 myotubes,taking 1 as the lead.In high-fat diet(HFD)and STZ induced diabetic mice,9a significantly lowers blood glucose,improves glucose tolerance,and especially alleviates diabetic nephropathy and islet damage.Mechanism study indicates that 9a simultaneously targets mitochondrial complex I to increase AMP/ATP ratio,as well as liver kinase B1(LKB1)and calcium/calmodulindependent protein kinase(Ca MKK),which synergistically activates AMPKαand then stimulates glucose transporter 4(GLUT4)membrane translocation and 2-deoxyglucose(2-DG)uptake to exert anti-diabetic efficacy.Therefore,compound 9a with a novel structure is a promising anti-diabetic candidate with the advantage of multiple-target mechanism,worthy of further investigation.
基金Acknowledgement We are grateful for the National Basic Research Program of China (No. 2011CB833200), the National Natural Science Foundation of China (Nos. 20772051, 20972058), the "111" Program from MOE of P. R. China and the Fundamental Research Funds for the Central Universities (lzujbky-2012-90).
文摘The stereoselective syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reaction of chiral tricyclic iminolactone and aldehyde.
文摘Natural products and their derivatives repre- sent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have been shown to be effective agents in the clinic or in preclinical settings. In the present review, we present a story of discovery, synthesis and evaluation of three synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs as cancer therapeutic agents. Chemical synthesis of these compounds (BA-TPQ, TBA-TPQ, and TCBA-TPQ) has been accomplished and the mechanisms of action (MOA) and structure-activity relationships (SAR) have been investigated. In the past, the complexity of chemical synthesis and the lack of well-defined MOA have dampened the enthusiasm for the development of some makaluvamines. Recent discovery of novel molecular targets for these alkaloids (unrelated to inhibition of Topoisomerase II) warrant further consideration as clinical candidates in the future. In addition to the establishment of novel synthetic approaches and demonstration of in vitro and in vivo anticancer activities, we have successfully demonstrated that these makaluvamines attack several key molecular targets, including the MDM2-p53 pathway, providing ample opportunities of modulating the compound structure based on SAR and the use of such compounds in combination therapy in the future.
文摘One monoaromatic tricyclic diterpane and two aromatic tricyclic diterpanes were found in three low-maturity source rocks and five crude oils of the Tertiary Shahejie Formation in Shengli Oil Field. The compounds found include C19H28 (m/z 145, M+ 256) ring-C monoaromatic tricyclic terpane, C17H20 (m/z 209, M+ 224) and C18H22 (m/z 223,M+ 238) rings-B,C diaromatic diterpanes. The results show that these compounds are biomarkers of immature organic matter with a stability sequence of C18H22 】 C17H20 】 C19H28. The cleavage of ring-D of pentacyclic triterpanoids, such as oleanene, hopene, fernene, ursene, in the early stage of diagenesis may be one of the origin pathways of rings-B, C diaromatic tricyclic diterpanes.
基金supported by the National Natural Science Foundation of China(Grant No.20072025)Promoted Research Programs of Chinese Academy of Sciences.
文摘One-electron oxidation of N-4-desmethylwyosine (dYt), a derivative of rare tricyclic nucleoside wyosine with several oxidative radicals, has been studied by using pulse radiolysis. The transient spectra of the radicals dYt˙+ and dYt(-H)˙ and the pK a of the radical cation were measured. The rate constants of reactions of dYt with SO 4 ˙? and CO 3 ˙? radicals have been determined and related reaction mechanisms were discussed.
基金supported by the National Natural Science Foundation of China(No.21502011)the Fundamental Research Funds for the Central Universitiesthe Chongqing Science&Technology Commission Project(No.cstc2016jcyjA0168)。
文摘Efficient synthetic routs for the direct and rapid construction of[5-6-6]ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully developed.For the daphmanidin A-type,the synthesis of[5-6-6]tricyclic framework utilize a HCl-mediated intramolecular Aldol reaction to construct the bicyclo[2.2.2]octane core and a thermal condensation to afford the ABC ring system.In addition,for the calyciphylline A-type,an improved synthesis of ABC[5-6-6]tricyclic system was developed,featuring an introduction of methyl ester group at C2 before the Pd-catalyzed intramolecular oxidative alkylation to construct the desired bowl-shape tricyclic core with stereochemical control.
基金the National Natural Science Foundation of China(Nos.21372149,21572125)the Fundamental Research Funds for the Central Universities of China(No.GK201703023)Shaanxi Normal University。
文摘The synthesis of the ACE tricyclic system of daphnicyclidin A and dehydroxymacropodumine A are developed.The key reactions include an efficient aldol reaction to introduce chiral fragment 33 for further construction of piperidine ring B and seven-membered ring C, a nucleophilic addition of lithium pentene to aldehyde for installation of ring E,and a photocatalytic decarboxylation conjugate addition to construct ring C.
文摘Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues re- ported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.
基金Supported by the Wuhan Science and Technology Projec(201250499145-20)Hubei Construction Science and Technology Projec(2011)
文摘The spectral moments are the important algebraic invariants of graphs.In this paper,on the basis of definitions of tricyclic graphs,base and the sequence of spectral moments,respectively,we study tricyclic graphs with given bases on the lexicographical order of the spectral moments sequence,and find the last and the first graphs.The results is very helpful for studying all tricyclic graphs ordering by spectral moments.