A Facile Synthesis and Studies of Some New Chalcones and Their Derivatives Based on Heterocyclic Ring

Chalcones (6a-f) have been prepared by the condensation of ketone (5) and different aromatic and heterocyclic aldehydes. These chalcones (6a-f) on treatment with guanidine hydrochloride and phenyl hydrazine hydrochloride in presence of alkali give aminopyrimidines (7a-f) and phenylpyrazolines (8a-f) respectively. All the newly synthesized compounds have been characterized on the basis of IR, H NMR spectral data as well as physical data. Antibacterial activity (minimum inhibitory concentration MIC) against Gram-positive S. aureus MTCC 96 and S. pyogeneus MTCC 442 and Gram-negative P. aeruginosa MTCC 1688 and E. coli MTCC 443 bacteria, as well as antifungal acivity (MIC) against C. albicans MTCC 227, A. niger MTCC 282 and A. clavatus MTCC 1323 were determined by broth dilution method.


Introduction
Commonly α, β -unsaturated ketone is known as chalcone.Chalcones 1,2 are very reactive compounds and increase their reactivity due to keto-ethylinic type of conjugated double bond system present in the molecule.Chalcones have occupied unique place in medicinal and biological chemistry due to their diverse pharmacological properties such as anticancer 3 , anti-inflammatory 4 , antiviral 5 and antibacterial 6 etc….Five membered heterocyclic like pyrazolines have found wide application as pharmaceutical and agrochemical agents.Pyrazoline derivatives have been found to possess wide range of therapeutic activities such as diuretic 7 , antifungal 8 , analgesic 9 , and mollucicidal 10 etc….Pyrimidine derivatives play a vital role in many biological processes and in synthesis of many drugs.Many pyrimidine derivatives have displayed diverse biological activities such as antitumor 11 , hypnotensive 12 , antiulcer 13 , and anticonvulsant 14

etc…
In view of the above and in a continuation of our work [15][16][17] on chalcones and its derivatives, we herein report a new series of chalcones (6a-f), aminopyrimidines (7a-f), and phenylpyrazolines (8a-f).

Experimental
All melting points were determined in open capillary and are uncorrected.The IR spectra were recorded on a FTIR -8400 spectrometer. 1H NMR spectra on a Bruker Avance DPX 400 MHz spectrometer with CDCl 3 as a solvent and tetramethylsilane (TMS) as internal standard.The chemical shifts are expressed in parts per million (ppm) downfield from the internal standard and signals are quoted as s (singlet) and m (multiplate).Analytical separation was conducted with silica Gel 60 F-254 (Merck) plates of 0.25 mm thickness eluted with toluene : acetone (10 : 2 v/v) and were visualized with UV (254 nm) or iodine to check the purity of the synthesized compounds.

Results and Discussion
The in vitro antibacterial and antifungal activities of the compounds are shown in (Table 2).The MICs (μg/mL) were carried out by broth microdilution method as described by Rattan 18 .The newly synthesised compounds (6a-f), (7a-f) and (8a-f) were screened for their antibacterial activity against two Gram positive bacteria srains: S. aureus MTCC96 and S. pyogenes MTCC442 and two Gram negative bacteria E.coli MTCC443 and P. aeruginosa MTCC1688 and compared with standard drug: Ampicillin and Antifungal activity against C. albicans MTCC227, A. niger MTCC282 and A. clavatus MTCC1323 organisms was determined by same method and compared with standard drug: Griseofulvin.

Conclusion
Compounds having methoxy and phenoxy groups have exhibited more antimicrobial activity.These results suggest that the chalcone derivatives have excellent scope for further development as commercial antimicrobial agents.Further experiments were needed to elucidate their mechanism of action.