RESUMEN
Thieno[2,3-b]pyridine derivatives DATPa-c have been synthesized based on Thorpe-Ziegler Cyclization. The reaction of arylidene malononitrile derivatives (Ia-c) with thiocyanoacetamide (II) in basic medium (piperidine) followed by alkylation using ethyl chloroacetate and finally, cyclization in sodium ethoxide yielded DATPa-c. Thieno[2,3-b]pyridine-chitosan nanocomposites CS-DATPa-c were prepared from the DATPa-c and CS nanoparticles using sodium tripolyphosphate (TPP). CS-DATPa-c nanocomposites were characterized using FTIR, TEM and XRD techniques and showed a relatively narrow size distribution of monodispersed nanoparticles with the average size of 14-78 nm. The in vitro release studies of CS-DAΤPa-c nanocomposites were investigated and showed that the drug release rate is pH-dependent and the trend is as follows: basic > neutral > acidic. The faster release rate in basic medium effectively prolongs drug delivery in gastric pH. Additionally, the antibacterial investigation showed that DATPa-c and CS-DATPa-c nanocomposites exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria but CS-DATPa-c nanocomposites showed much higher antibacterial activity compared to the DATPa-c, which in agreement with the particle size measurements as DATPa-c are in the bulky structure whereas, CS-DATPa-c are in the nanostructure. The results may have applications of drug design for colon targeting.