Synthesis, degradation kinetics and in vitro antimicrobial activity of tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives of some beta-amino acids.
Two series of tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives were synthesized, 2a-f and 3a-f, by incorporation of beta-alanine and beta-phenylalanine, respectively, at the 5th position of the THTT moiety. Structures of these derivatives were verified by spectral and elemental methods of analyses. The lipophilic properties of the synthesized derivatives, expressed as calculated log P (Clog P), revealed that the beta-phenylalanine derivatives, 3a-f, have enhanced lipophilic characters compared to the corresponding beta-alanine analogues, 2a-f. The stability of the synthesized derivatives in aqueous buffer solution of pH 7.4, and in 80% human plasma was studied at 37 degrees C using high pressure liquid chromatography. As a general pattern, under the investigation conditions beta-phenylalanine derivatives were more labile and susceptible for chemical and enzymatic degradation than the corresponding beta-alanine analogues. Furthermore, the degradation rates of the synthesized derivatives affected by the variation of substituents on N-3 of the THTT moiety. The anti-fungal activity of the synthesized compounds was tested in vitro against different strains of fungi using the standard agar disk diffusion method. beta-Alanine derivatives, 2e and 2f, bearing an aralkyl group on the 3ed position of the THTT moiety exhibited antifungal activity against C. albicans and F. oxysporum. Furthermore, 2a, which is also a beta-alanine derivative bearing an ethyi group on the 3ed position of the THTT moiety solely showed a significant in vitro anti-bacterial activity against Bacillus serreus (Gram positive) and Serratia rhodnii (Gram negative).
Aboul-Fadl
Tarek
T
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt. fadl@acc.aun.edu.eg
Khallil
Abdel-Raouf
AR
D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010649:Phenylalanine / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013871:Thiones / Q000138:chemical synthesis* / Q000494:pharmacology*
D000596:Amino Acids; D000890:Anti-Infective Agents; D008055:Lipids; D013843:Thiazines; D013871:Thiones; C477840:tetrahydro-2H-1,3,5-thiadiazine-2-thione; D010649:Phenylalanine; D000409:Alanine