Reactivities of 4-amino salicylic acid and its ‘Green’ inhibition into nano sized β-cyclodextrin for Anti-Tuberculosis drug delivery

Abstract

In the present work, 4-amino salicylic acid (PAS) which is an oral antibiotic against tuberculosis is being investigated for its potential “Green” effectivity in trapped conditions within nano sized good solubilizing drug receptor. The process is totally “green” as no toxic materials, chemicals and solvent other than water has been used throughout the encapsulation /complexation process. Cyclodextrin glycosyltransferase (3CGT) and its by-product beta (β)-cyclodextrin (β-CD) usually act as nano sized good solubilizing agents for many drugs. In aqueous medium both 3CGT and β-CD can create drug: receptor complex by encapsulating the drug into its nano sized cavity and can increase the aqueous solubility of probe drug depending on the ionic strength. PAS was initially screened by its drug likeness properties by ADMET analysis. Structural analysis and chemical reactivity of PAS have been checked by density functional theory with basis set B3LYP/6-311G++*(d,p) in aqueous environment. The electronic properties (atomic charges, electrostatic potential, and uv–visible absorption & fluorescence analysis) have been studied to check the possibility of 1:1 complex formation between PAS: β-CD. To understand the type and strength of interactions between PAS and receptor, molecular docking and molecular dynamics simulations have been performed between PAS and cyclodextrin glycosyltransferase (3GGT). PAS has shown strong interaction possibilities both as 1:1 inclusion complex (PAS: β-CD) and as PAS: 3CGT complex. Our in-silico and experimental outcomes have recommended 4-amino salicylic acid’s better efficacy as a promising inhibitor inside cyclodextrin nano-cavity for targeting tuberculosis.