Stereoselective analysis of thioridazine-2-sulfoxide and thioridazine-5-sulfoxide: an investigation of rac-thioridazine biotransformation by some endophytic fungi.
The purpose of this study was to develop a method for the stereoselective analysis of thioridazine-2-sulfoxide (THD-2-SO) and thioridazine-5-sulfoxide (THD-5-SO) in culture medium and to study the biotransformation of rac-thioridazine (THD) by some endophytic fungi. The simultaneous resolution of THD-2-SO and THD-5-SO diastereoisomers was performed on a CHIRALPAK AS column using a mobile phase of hexane:ethanol:methanol (92:6:2, v/v/v)+0.5% diethylamine; UV detection was carried out at 262 nm. Diethyl ether was used as extractor solvent. The validated method was used to evaluate the biotransformation of THD by 12 endophytic fungi isolated from Tithonia diversifolia, Viguiera arenaria and Viguiera robusta. Among the 12 fungi evaluated, 4 of them deserve prominence for presenting an evidenced stereoselective biotransformation potential: Phomopsis sp. (TD2) presented greater mono-2-sulfoxidation to the form (S)-(SE) (12.1%); Glomerella cingulata (VA1) presented greater mono-5-sulfoxidation to the forms (S)-(SE)+(R)-(FE) (10.5%); Diaporthe phaseolorum (VR4) presented greater mono-2-sulfoxidation to the forms (S)-(SE) and (R)-(FE) (84.4% and 82.5%, respectively) and Aspergillus fumigatus (VR12) presented greater mono-2-sulfoxidation to the forms (S)-(SE) and (R)-(SE) (31.5% and 34.4%, respectively).
Borges
Keyller Bastos
KB
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-903, Brazil.
De Souza Borges
Warley
W
Pupo
Mônica Tallarico
MT
Bonato
Pierina Sueli
PS
D000688:Amylose / Q000031:analogs & derivatives / Q000737:chemistry; D014150:Antipsychotic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000302:isolation & purification / Q000378:metabolism; D019659:Asteraceae / Q000382:microbiology*; D001711:Biotransformation; D002021:Buffers; D002219:Carbamates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D003470:Culture Media / Q000737:chemistry; D004048:Diethylamines / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D004986:Ether / Q000737:chemistry; D005658:Fungi / Q000302:isolation & purification / Q000378:metabolism*; D006586:Hexanes / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D020081:Phyllachorales / Q000302:isolation & purification / Q000378:metabolism; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013881:Thioridazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism
D014150:Antipsychotic Agents; D002021:Buffers; D002219:Carbamates; D003470:Culture Media; D004048:Diethylamines; D006586:Hexanes; D012997:Solvents; C445088:chiralpak AS; C529599:thioridazine-2-sulfoxide; D004986:Ether; D000431:Ethanol; C041140:thioridazine-5-sulfoxide; D000688:Amylose; C034281:diethylamine; D013881:Thioridazine; D000432:Methanol