Synthesis and In Vitro Antimicrobial , Anthelmintic and Insecticidal Activities Study of 4 ( 4 '-Bromophenyl )-6-substituted-aryl-1-acetyl pyrimidine-2-thiols

A new series of 4(4'-bromophenyl)-6-substituted aryl-1-acetyl pyrimidine-2-thiol derivatives were synthesized by heating chalcones with thiourea, in the presence of ethanolic potassium hydroxide, followed by treatment with acetyl chloride. The structure of the compounds was characterized by IR and H NMR spectral study and elemental analysis. The compounds were screened for their antimicrobial, anthelmintic and insecticidal activities. All the compounds exhibited significant to moderate biological activities.


Experimental
The melting points were recorded by open capillary method and are uncorrected.IR spectra (ν max in cm -1 ) were recorded on a Shimadzu FTIR 8300 spectrophotometer, using KBr pellets.The H 1 NMR spectra were recorded on a DRX-300 (300 MHz) instrument using CDCl 3 as solvent (Chemical Shift in δ ppm), using TMS as internal standard.The completion of reactions was monitored by TLC.

Synthesis of 4-bromochalcones (1a-j)
4-Bromoacetophenone (0.01 mol) and anisaldehyde (0.01 mol) were stirred in ethanol (20 mL) and to it 10 mL of 40% NaOH solution was added.The mixture was kept overnight at room temperature.The contents were then poured on crushed ice and acidified with dil.HCl.The solid was filtered, dried and recrystallised from ethanol.The other chalcones were prepared with the same procedure using different aromatic aldehydes.

Antimicrobial activity
The synthesized compounds (3a-j) were screened for their in vitro antimicrobial activity against, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus and antifungal activity against, Aspergillus niger, Aspergillus flavus, Trichoderma viride, Candida albicans by measuring the zone of inhibition in mm.The antimicrobial activity was performed by standard filter paper disc diffusion method [16][17] and zone of inhibition is reported in the Table 3. Streptomycin and nystatin were used as standard drug for antibacterial and antifungal activities respectively.Nutrient agar was employed as culture medium and DMSO, was used as solvent.In vitro anthelmintic activity 18 In vitro anthelmintic screening studies of compounds 3a-j were performed by the Watkins technique, against common Indian earthworm 'P.posthuma'.For this purpose 4% and 2% solutions of the synthesized pyrimidine derivatives and standard drug piperazine hydrochloride in ethylene glycol were used for experiment.The experiments were performed in duplicate and average values of paralytic time and lethal time in minutes have given in the Table 3. Insecticidal activity [19][20] Adult cockroaches (P.americana) were selected for the testing of, in vitro insecticidal activity.4% solutions of synthesized pyrimidine derivatives and standard drug cypermethrin (w/v), in acetone were used for experiment.The time of death of cockroaches was noted, on an average and denoted as KD (Knock Down) value in minutes.For each sample three replication were performed and same experiments were performed with standard drug.

Conclusion
All the synthesized pyrimidine-2-thiols 3(a-j) have given appreciable yield with satisfactory elemental analysis.It is inferred from the Table 2, 3 & 4, that synthesized compounds 3a-j, have shown significant antibacterial activity, good to moderate antifungal activity and significant anthelmintic and insecticidal activities, due to the presence of thio group, which enhance the respective activities with varied substituent groups, against selected pathogens and organisms.

Table 1 .
Physical data of compounds 3a-j.