Abstract

Gawade Baliram*

ABSTRACT

A promising approach that has been incorporated to fight bacterial pathogens are those which interfere with the Quorum sensing (QS), a main signal transduction system. Here, we have described new hybrids for the inhibition of QS mediated by PQS of P. aeruginosa one of the multidrug-resistant and highly virulent pathogens that desperately need new antibacterial therapeutic approaches. The synthesis of 12 compounds we performed according to the standard techniques with the help of which we established the connection between halogen- substituted anthranilic acids and 4-(2-aminoethyl/4-aminobuthyl) amino-7-chloroquinoline connected through 1,3,4-oxadiazole. The antibiofilm activities were firstly tested by Gram- negative Photobacterium violaceum-based reporter that distinguished compounds 15–19 and 23 as the compounds exerting the highest anti-QS and minimal bactericidal effects at the same time in one experiment. Subsequently, these five compounds were tested on P. aeruginosa PAO1 for their antibiofilm potential factors such as; their effectiveness in stopping biofilm formation, their effectiveness in eliminating prior biofilm formation as well as effectiveness in quenching bacterial virulence employing pyocyanin as a biomarker. The highest activities of antibiofilm effect of Compound 15 were reducing biofilm formation in 48 h by 49% and pre formed biofilm masses by 25%, respectively. In contrast, the compound 23 demonstrated the maximum ant virulence property and almost eliminated the pyocyanin production by more than 70%. Therefore, the present investigation demonstrates that among the synthesized 1, 3, 4- oxadiazoles 15 and 23 could be further explored for antipseudomonal activity. Furthermore, more advanced interactive QS systems should be taken into account to have maximum anti-QS effect against this clinically relevant species.