Synthesis and evaluation of novel 3, 4-dihydropyrimidin-2(1H)-thione based pongamol conjugates as antibacterial agents

Pongamol, the furanochalcone present in different parts of karanj (Pongamia glabra) tree has been taken in this investigation to undergo Biginelli reaction with thiourea and p-substituted benzaldehydes. These three component cyclo-condensation reaction in acetic acid catalyzed by hydrochloric acid resulted in the formation of a new series of 4-methoxybenzofuran-5oyl conjugated 3,4-dihydropyrimidin-2(1H)-thiones (4a to 4g). Synthesized new derivatives were characterized by NMR (H-1 and C-13) and mass (HRESI-MS). Screening of the antibacterial activity against some selected bacterial strains showed that the derivatives 4a, 4b, 4c and 4f exhibited excellent antibacterial activity specifically against Klebsiella planticola. Derivative 4c also showed potency against Escherichia coli and Micrococcus luteus. Based on this promising result, further screening of these four compounds was carried out for minimum bactericidal concentration (MBC) and anti-biofilm activity. Excellent bactericidal activity (MBC, 1.9 mu g/mL) of compound 4c and 4f was observed respectively against M. luteus and K. planticola, at par with the reference drug ciprofloxacin. Potent derivatives were also assayed for anti-biofilm activity. Results indicated that the compound 4f exhibited excellent anti-biofilm activity against K. planticola with IC50 value 3.6 mu g/mL equivalents to ciprofloxacin. Thus, this new class of 4-methoxybenzofuran-5-oyl conjugated 3,4-dihydropyrimidin-2(1H)-thione derivatives has the potential to be an active bactericidal agent with anti-biofilm activity. [GRAPHICS] .

Automated summary

This study focused on the synthesis and characterization of a new class of derivatives called 4-methoxybenzofuran-5-oyl conjugated 3,4-dihydropyrimidin-2(1H)-thiones. These derivatives showed excellent antibacterial activity against Klebsiella planticola and also exhibited potency against Escherichia coli and Micrococcus luteus. The compound 4f demonstrated strong anti-biofilm activity against K. planticola. These findings suggest that these derivatives have the potential to be effective bactericidal agents with anti-biofilm activity.