Synthesis of novel 2, 3, 5-tri-substituted thiazoles with anti-inflammatory and antibacterial effect causing clinical pathogens

Background: The present work is an extension of ongoing efforts toward the development and identification of new molecules as monotherapy displaying anti-inflammatory and anti-infective activities and a wide-range of gastrointestinal selectivity. A series of novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and evaluated for their in-vitro and in-vivo anti-inflammatory activities. Synthesized trisubstituted thiazole compounds were also evaluated for their potential antibacterial activity against clinical pathogens causing infectious disease. Material and Method: The structures of synthesized compounds were characterized by FTIR, H-1 NMR, Mass spectroscopic techniques and evaluated for their in-vitro and in-vivo anti-inflammatory effects using the human red blood cell (HRBC) membrane stabilization method and a carrageenan-induced rat paw oedema model, respectively, Diclofenac sodium and Ibuprofen were used as standard drugs. The synthesized compounds AR-17a to AR-27a screened for their in-vitro antibacterial activity against the gram-positive bacteria Staphylococcus aureus (ATCC25923) and Enterococcus faecalis (ATCC29212) and the gram-negative bacteria Escherichia coli (ATCC8739) and Pseudomonas aeruginosa (ATCC9027) using ciprofloxacin and cefdinir as standard drugs. Result: Compounds AR-17a and AR-27a elicited maximum anti-inflammatory activity, providing 59% and 61% protection at 20 mg/kg, respectively, in the inflamed paw model. Among the tested compounds, AR-17a (6.25), (54) and AR-27a (1.56), (52) had the least minimum inhibitory concentration values and the highest zone of inhibition, indicating their marked antibacterial activities. The lowest conc. were observed at 1.56, 6.25 tig/mL for inhibition of bacteria by most of the compounds. Conclusion: Novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and characterized successfully. The preliminary screening revealed that these compounds possess promising anti-inflammatory and antibacterial activities. In addition, the objective of the study was achieved with few of the promising structures like AR-17a to AR-27a, which are prove to be potential monotherapy candidates for the treatment of chronic inflammatory diseases and bacterial infections. (C) 2020 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences.