HYDROPHOBIC INTERACTION OF 2-TRIFLUOROMETHYL-N10-SUBSTITUTED PHENOXAZINES WITH BOVINE SERUM ALBUMIN AND REVERSAL OF DRUG RESISTANCE IN BACTERIAL CELLS
Keywords:Hydrophobic interaction, Phenoxazines, Bacterial drug resistance, Bovine serum albumin
Objective: The objective of this study was to report the hydrophobic interaction of 2-trifluoromethyl-N10-substituted phenoxazines with bovine serum albumin and reversal of drug resistance in bacterial cells.
Methods: Binding of six compounds, 10-[3'-N-morpholinopropyl]-2-trifluoromethyl phenoxazine (1C), 10-[4'-N-morpholinobutyl]-2-trifluoromethyl phenoxazine (2C), 10-[3'-N-pyrrolidinopropyl]-2-trifluoromethyl phenoxazine (3C), 10-[4'-N-pyrrolidinobutyl]-2-trifluoromethyl phenoxazine (4C), 10-[N-piperidinoacetyl]-2-trifluoromethyl phenoxazine (5C), and 10-[N-pyrrolidinoacetyl]-2-trifluoromethyl phenoxazine (6C), to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The binding of these compounds to BSA has been characterized by percentage of bound drug (Î²), the association constant (K), the apparent binding constant (k) and free energy (âˆ†Fo). The binding of phenoxazine derivatives to BSA, a serum protein that binds and transports small molecules, is correlated with their partition coefficients. Further, the ability of the phenoxazines (1C-6C) on the antibacterial activity of five antibiotics, kanamycin, spectinomycin, gentamycin, streptomycin and benzylpenicillin was examined for their ability to reverse the resistance of E. coli K12 MG 1655 and E. coli ST 58.
Results: The results of displacing experiments reveal that the phenoxazine benzene rings and tertiary amines attached to the side chain of phenoxazine moiety are bound to a hydrophobic region on the albumin molecule. Among the compounds examined the butyl series seems to possess better reversing ability, suggesting that the activity could be related to lipophilicity and the extent of binding to BSA.
Conclusions: Phenoxazines are bound to albumin by hydrophobic interactions of their benzene rings. The alkyl side chain, particularly butyl chain of phenoxazines intensifies the interaction of phenoxazines with BSA. The compound that binds to a greater extent with protein possesses more activity for reversing of drug resistance.
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