On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacologica...On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacological evaluation showed that the configuration and the substituents on the phenyl ring and the nitrogen of amides, and substituents on the double bond displayed an important effect on the anticonvulsant activity.For studying the effect of the modification of structure to anticonvulsant activity, Hansch approach was employed to study the QSAR among 38 cinnamamides, and Hopfinger' s MSA was employed to study the MSA-QSAR among 26 cinnamamides.展开更多
Two new cinnamamide derivatives designated as cimicifugamide((?))and isocimicifu- gamide((?)),have been isolated from the rhizomes of Cimicifuga dahurica(Turcz.)Maxim..Their structures were established based on spectr...Two new cinnamamide derivatives designated as cimicifugamide((?))and isocimicifu- gamide((?)),have been isolated from the rhizomes of Cimicifuga dahurica(Turcz.)Maxim..Their structures were established based on spectral evidence as N-(3'-methoxy-4'-hydroxyphenethyl)- 4-0-β-D-galactopyrano syl-ferulamide(E)and N-(3'-methoxy-4'-hydroxyphenetnyl)-4-0-β-D-ga- lactopyranosyl-isoferulamide(Z)respectively.展开更多
Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first...Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first reported in this note. Cinnamamides display a variety of pharmacological actions. The relationship between their structure and anticonvulsant activity in particular has been studied extensively. Literature reported that the partition coefficient (log p, octanol/water), dipole moment and inductive effect index (Ⅰ) of the compounds,展开更多
Arylation of acrylamide and acrylonitrile were carried out with various arenediazonium tetrafluoroborates in the presence of a catalytic amount of Pd(OAc)(2) in ethanol and a variety of substituted (E)-cinnamamides an...Arylation of acrylamide and acrylonitrile were carried out with various arenediazonium tetrafluoroborates in the presence of a catalytic amount of Pd(OAc)(2) in ethanol and a variety of substituted (E)-cinnamamides and (E)-cinnamonitriles were obtained in high yields under mild reaction conditions.展开更多
The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy,and activating Nur77’s non-genotypic anticancer function has demonstrated strong therapeutic potential.However,few Nur77 site B...The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy,and activating Nur77’s non-genotypic anticancer function has demonstrated strong therapeutic potential.However,few Nur77 site B ligands have been identified as excellent anticancer compounds.There are no co-crystal structures of effective anticancer agents at Nur77 site B,which greatly limits the development of novel Nur77 site B ligands.Moreover,the lack of pharmaceutical ligands restricts Nur77’s therapeutic proof of concept.Herein,we developed a first-in-class Nur77 site B ligand(NB1)that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria.The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode.Importantly,NB1 showed favorable pharmacokinetic profiles and safety,as evidenced by its good oral bioavailability in rats and lack of mortality,bodyweight loss,and pathological damage at the 512.0 mg/kg dose in mice.Furthermore,oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model.Together,our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.展开更多
基金Projects Supported by the National Fund of Natural Sciences
文摘On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacological evaluation showed that the configuration and the substituents on the phenyl ring and the nitrogen of amides, and substituents on the double bond displayed an important effect on the anticonvulsant activity.For studying the effect of the modification of structure to anticonvulsant activity, Hansch approach was employed to study the QSAR among 38 cinnamamides, and Hopfinger' s MSA was employed to study the MSA-QSAR among 26 cinnamamides.
文摘Two new cinnamamide derivatives designated as cimicifugamide((?))and isocimicifu- gamide((?)),have been isolated from the rhizomes of Cimicifuga dahurica(Turcz.)Maxim..Their structures were established based on spectral evidence as N-(3'-methoxy-4'-hydroxyphenethyl)- 4-0-β-D-galactopyrano syl-ferulamide(E)and N-(3'-methoxy-4'-hydroxyphenetnyl)-4-0-β-D-ga- lactopyranosyl-isoferulamide(Z)respectively.
文摘Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first reported in this note. Cinnamamides display a variety of pharmacological actions. The relationship between their structure and anticonvulsant activity in particular has been studied extensively. Literature reported that the partition coefficient (log p, octanol/water), dipole moment and inductive effect index (Ⅰ) of the compounds,
基金This work was supported by the Natural Science Foundation of Jiangxi Province.
文摘Arylation of acrylamide and acrylonitrile were carried out with various arenediazonium tetrafluoroborates in the presence of a catalytic amount of Pd(OAc)(2) in ethanol and a variety of substituted (E)-cinnamamides and (E)-cinnamonitriles were obtained in high yields under mild reaction conditions.
基金supported by grants from the National High Level Hospital Clinical Research Funding&Elite Medical Professionals Project of China-Japan Friendship Hospital(2023-NHLHCRF-DJMS-03&NO.ZRJY2023-GG07)the Fundamental Research Funds for the Central Universities of China(20720180051 and 3332023095)+3 种基金the National Key Research and Development Program of China(2022YFF0710803 and 2022YFF0710800)the Joint Research Project of Fujian Provincial Health Commission and Fujian Department of Education(#2019-WJ-39,China)the National Natural Science Foundation of China(82300051)Fujian Provincial Health Commission(#2021zylc29,China).
文摘The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy,and activating Nur77’s non-genotypic anticancer function has demonstrated strong therapeutic potential.However,few Nur77 site B ligands have been identified as excellent anticancer compounds.There are no co-crystal structures of effective anticancer agents at Nur77 site B,which greatly limits the development of novel Nur77 site B ligands.Moreover,the lack of pharmaceutical ligands restricts Nur77’s therapeutic proof of concept.Herein,we developed a first-in-class Nur77 site B ligand(NB1)that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria.The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode.Importantly,NB1 showed favorable pharmacokinetic profiles and safety,as evidenced by its good oral bioavailability in rats and lack of mortality,bodyweight loss,and pathological damage at the 512.0 mg/kg dose in mice.Furthermore,oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model.Together,our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.
