RESUMO
Oligostilbenoids are polyphenols that are widely distributed in nature with multifaceted biological activities. To achieve biomimetic synthesis of unnatural derivatives, we subjected three resveratrol analogues to oligomerization by means of one-electron oxidants. Upon varying the metal oxidant (AgOAc, CuBr(2), FeCl(3)6 H(2)O, FeCl(3)6 H(2)O/NaI, PbO(2), VOF(3)), the solvent (over the whole range of polarities), and the oxygenated substitution pattern of the starting material, stilbenoid oligomers with totally different carbon skeletons were obtained. Here we propose to explain the determinism of the type of skeleton produced with the aid of hard and soft acid/base concepts in conjunction with the solvating properties of the solvents and the preferred alignment by the effect of pi stacking.
Assuntos
Biomimética , Oxidantes/química , Solventes/química , Estilbenos/síntese química , Catálise , Dimerização , Flavonoides/síntese química , Flavonoides/química , Estrutura Molecular , Fenóis/síntese química , Fenóis/química , Polifenóis , Resveratrol , Estereoisomerismo , Estilbenos/químicaRESUMO
A new steroidal alkaloid, isosarcodine (1) along with four known bases, sarcorine (2), sarcodine (3), sarcocine (4) and alkaloid-C (5) were isolated from the MeOH extract of Sarcococca saligna. The structures of these alkaloids were identified by spectral data interpretation. These compounds were subjected to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition studies, and were found to be noncompetitive inhibitors of AChE (Ki = 21.8, 90.3, 32.2, 16.0 and 50.0 microM, respectively) and uncompetitive or noncompetitive inhibitors of BChE (Ki = 8.3, 7.5, 15.6, 5.0 and 12.0 microM, respectively). The compounds (2-5) also showed dose-dependent spasmolytic activity in the rabbit jejunum intestinal preparations and also relaxed the high K+ (80 mM)-induced contraction, indicative of a calcium channel-blocking mechanism. Structure-activity relationship suggested that the nitrogen substituents at C-3 and/or C-20 of steroidal skeleton and the hydrophobic properties of the pregnane skeleton are the key structural features contributed to the inhibitory potency of these steroidal alkaloids against AChE and BChE.
Assuntos
Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Colinesterases/metabolismo , Parassimpatolíticos/farmacologia , Esteroides/farmacologia , Acetamidas/química , Acetamidas/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Alcaloides/química , Animais , Butirilcolinesterase/metabolismo , Buxaceae/química , Inibidores da Colinesterase/química , Colinesterases/química , Concentração Inibidora 50 , Jejuno/efeitos dos fármacos , Jejuno/fisiologia , Modelos Moleculares , Contração Muscular/efeitos dos fármacos , Parassimpatolíticos/química , Conformação Proteica , Coelhos , Esteroides/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Five new steroidal alkaloids, 5,14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-pregn-5,14-diene] (1), 14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-5alpha-pregn-14-ene] (2), 16-dehydrosarcorine [(20S)-20-(N,N-dimethylamino)-3beta-(N(a)-acetylamido)-5alpha-pregn-16-ene] (3), 2,3-dehydrosarsalignone [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-pregn-2,5-diene-4-one] (4), and 14,15-dehydrosarcovagine-D [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-2,14-diene-4-one] (5), were isolated from the ethanolic extract of Sarcococca saligna, along with two known bases, sarcovagenine-C (6) and salignarine-C (7). Their structures were elucidated on the basis of spectroscopic methods. All seven compounds were found to possess cholinesterase inhibitory potential in a concentration-dependent manner with the IC50 values ranging from 12.5 to 200 microM against acetylcholinesterase and from 1.25 to 32.2 microM against butyrylcholinesterase.
Assuntos
Colinesterases/metabolismo , Extratos Vegetais , Plantas/metabolismo , Pregnanos/química , Alcaloides/química , Alcaloides/farmacologia , Inibidores da Colinesterase/química , Inibidores Enzimáticos/farmacologia , Etanol/farmacologia , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Modelos Químicos , Espectrofotometria , Esteroides/química , Esteroides/farmacologia , Raios UltravioletaRESUMO
Two new steroidal alkaloids, salonine-A [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-14-en-2beta,4beta-diol] (1), and salonine-B [(20S)-20-(N,N-dimethylamino)-3beta-methoxy-pregn-5,16-diene] (2), were isolated from the MeOH extract of Sarcococca saligna, along with a known base, alkaloid-C (3). Their structures were elucidated on the basis of spectroscopic methods. All three compounds were found to be cholinesterase inhibitors.