Aqueous Synthesis and Biological Studies of Indole Derivatives
Aralihalli Sudhakara, Raghavendra Ramappa, Harish Basavanthappa Gowdru, Nataraja Gummanar, Ramesha Sonnappa, Mahadevan Kittappa Malavalli · American Journal of Heterocyclic Chemistry · 2016
One pot with expedient approach to the synthesis of 2,3-disubstituted indole derivatives using indium (III) trichloride through Fisher indole method has been developed, in aqueous media. The synthesized compounds were screened for their anti analgesic and antibacterial activity. All the six indole derivatives exhibited significant antibacterial activity against Pseudomonas aeruginosa when compared to standard drug Ciprofloxacin. Based on the results of antibacterial activity, the molecular docking of all six indole derivatives were performed against Pseudomonas elastase a matrix metalloproteinase from Pseudomonas aeruginosa were presumed as an infectious wound healer via MMP dependent pathway. The active pocket docked with indole derivatives at the torsional degree of freedom 0.5 units with Lamarckian genetic algorithm. The inhibitors binding is facilitated by direct hydrogen bond interactions with the residues residing in the catalytic motif of Pseudomonas elastase consisted of Ala113, His140, Glu141, His144, Glu164, Arg198 and His223. In addition, the inhibitors make many hydrophobic interactions with both the enzyme and the co-factor Zinc ion. In view of the possibility that the elastase is an important determinant in Pseudomonas infection, it is conceivable that inhibitors of the enzyme will reduce its destructive effects that may lead to new therapeutic intervention.