RESUMO
Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb = 8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.
Assuntos
Aporfinas/química , Receptor 5-HT2A de Serotonina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Serotonina/química , Agonistas de Receptores Adrenérgicos alfa 1/química , Agonistas de Receptores Adrenérgicos alfa 1/metabolismo , Aporfinas/metabolismo , Sítios de Ligação , Células HEK293 , Humanos , Cinética , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Receptor 5-HT2A de Serotonina/química , Receptor 5-HT2A de Serotonina/genética , Receptores Adrenérgicos alfa 1/química , Receptores Adrenérgicos alfa 1/genética , Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/química , Agonistas do Receptor 5-HT2 de Serotonina/metabolismo , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
This study seeks to investigate the relationship between the structural modification and bioactivity of a series of tribenzyltin complexes with different ligands and substitutions. Complexation with the N,N-diisopropylcarbamothioylsulfanylacetate or isonicotinate ligands enhanced the anticancer properties of tribenzyltin compounds via delayed cancer cell-cycle progression, caspase-dependent apoptosis induction, and significant reduction in cell motility, migration and invasion. Halogenation of the benzyl ring improved the anticancer effects of the tribenzyltin compounds with the N,N-diisopropylcarbamothioylsulfanylacetate ligand. These compounds also demonstrated far greater anticancer effects and selectivity than cisplatin and doxorubicin, which provides a rationale for their further development as anticancer agents.
Assuntos
Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Ligantes , Relação Estrutura-AtividadeRESUMO
The two Sn-O-C-C-C-O chelate rings in the title compound, [Sn(C(15)H(11)O(2))(2)Cl(2)]·0.5C(7)H(8), adopt envelope conformations, with the Sn atom deviating from the least-squares plane passing through the C and O atoms by 0.626â (1)â Å in one ring and by 0.690â (1)â Å for the other. The two planes are aligned at an angle of 59.6â (1)°. The Cl atoms occupy cis positions in the octa-hedral SnCl(2)O(4) coordination environment. The solvent mol-ecule is disordered about a center of inversion.