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0sman, Mahrous
- Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives of the Optical Isomers of Phenylalanine, Synthesis, Comparative Stability Study and Antifungal Activity
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Authors
Affiliations
1 Dept. Pharm. Med. Chem., Faculty of Pharmacy, Assiut University, Assiut-71526, EG
2 Dept. Pharm. Technology, Faculty of Pharmacy, Assiut University, Assiut-71526, EG
1 Dept. Pharm. Med. Chem., Faculty of Pharmacy, Assiut University, Assiut-71526, EG
2 Dept. Pharm. Technology, Faculty of Pharmacy, Assiut University, Assiut-71526, EG
Source
Scientia Pharmaceutica, Vol 70, No 4 (2002), Pagination: 359-378Abstract
In order to investigate the effect of the optical properties of the 5-substituent on the stability and the antifungal activity of tetrahydro-2H-1,3,5-thiadizine-2-thione (THTT) moiety, optical isomers and racemic mixture of phenylalanine were incorporated in the 5th position of THTT to afford derivatives 2a-g. Chemical and enzymatic stability of these derivatives were studied in vitro in aqueous buffer solution of pH 7.4, physiological pH, and 80% human plasma at 37°C using HPLC. The chemical and enzymatic degradation rates of the tested compounds revealed that the optical properties of the 5-substituent of THTT moiety have no role on their stability at the investigated media. However, the chemical nature of the 3-substiuents has a significant effect on their chemical and enzymatic liability as 3-aralkyl derivatives, 2f and 2g, were the least stable compounds under the investigation conditions. Solid state stability of these derivatives was studied using Differential Scanning Calorimetry (DSC). In spite of the distinguished DSC curves of the racemic cornpounds from that of the corresponding single optical isomers no constant pattern of their thermal stability was observed. The antifungal activity of 2a-g, was investigated in vitro against Candida albicans, C. parapsilosis and C. stellatoidea using tube dilution method. No role for the optical properties of the tested compounds on their antifungal activity was observed. The utmost antihngal activity revealed by compound 2g which has 3-phenethyl substituent. Moreover, 2g has the highest lipophilicity and the most susceptible compound for both chemical and enzymatic degradations.Keywords
Tetrahydro-2H-1,3,5-Thiadizine-2-Thione; Phenylalanin; Optical Isomers; Degradation Kinetics; Solid State Stability; Antifungal Activity.
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