Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from soph...Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.展开更多
We designed and synthesized 5 new compounds. Their chemical structures were confirmed by means of MS, HNMR andelemental analysis. FPA was tested for positive inotropic activity. The results showed that FPA could incre...We designed and synthesized 5 new compounds. Their chemical structures were confirmed by means of MS, HNMR andelemental analysis. FPA was tested for positive inotropic activity. The results showed that FPA could increase the contrastive amplitudeof isolated atrium of guinea pigs and had no influence upon rhythm of the hearts.展开更多
Isoflavonoids possess broad activities besides cardiovascular activity.3 phenyl 4(1H)quinolinone derivatives are isosteres of isoflavonoids.They have similar spatial structures.Eight 3 phenyl 4(1H)quinolinone halide d...Isoflavonoids possess broad activities besides cardiovascular activity.3 phenyl 4(1H)quinolinone derivatives are isosteres of isoflavonoids.They have similar spatial structures.Eight 3 phenyl 4(1H)quinolinone halide derivatives were synthesised for studying their biological activities especially cardiovascular activity.Their chemical structures were confirmed by 1 H NMR,MS and IR.The preliminary tests with isolated heart of rabbits indicated that both mixtures,A 1B 1,A 2B 2,had more positive inotropic effect than vesnarinone which appeared on the market in Japanese.The results of the pharmacological tests showed that the two mixtures did not affect the blood pressure and respiration of the dogs.展开更多
基金supported by the National Natural Science Foundation of China(No.81473248)Tianjin Medical University General Hospital Funding(ZYYFY2015030)
文摘Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
文摘We designed and synthesized 5 new compounds. Their chemical structures were confirmed by means of MS, HNMR andelemental analysis. FPA was tested for positive inotropic activity. The results showed that FPA could increase the contrastive amplitudeof isolated atrium of guinea pigs and had no influence upon rhythm of the hearts.
文摘Isoflavonoids possess broad activities besides cardiovascular activity.3 phenyl 4(1H)quinolinone derivatives are isosteres of isoflavonoids.They have similar spatial structures.Eight 3 phenyl 4(1H)quinolinone halide derivatives were synthesised for studying their biological activities especially cardiovascular activity.Their chemical structures were confirmed by 1 H NMR,MS and IR.The preliminary tests with isolated heart of rabbits indicated that both mixtures,A 1B 1,A 2B 2,had more positive inotropic effect than vesnarinone which appeared on the market in Japanese.The results of the pharmacological tests showed that the two mixtures did not affect the blood pressure and respiration of the dogs.
