Synthesis and characterization of biologically potent chalcone bearing 1,3,4-oxadiazole linkage

In this article, we have described to design and synthesized a series of substituted chalcone based 1,3,4-oxadiazole derivatives. Titled compounds (E)-S-(-5-phenyl-1,3,4-oxadiazol-2yl) 2-(4-(3-(5-methyl-3oxo-2(p-tolyl)-2,3-dihydro-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-yl)phenoxy) etanethioate (III1-6) were synthesized using of derivatives of S-(-5-phenyl-1,3,4 oxadiazole-2-yl)2chloroethaethioate (I1-6) were reacted with (E)-4-(3-(4-hydroxyphenyl)acryloyl)-5-methyl-2(ptolyl)-1H-pyrazol-3(2H)-one (II) in presence of K2CO3 in DMF as a solvent. The synthesized compounds were evaluated for their antimicrobial activity. The newly synthesized compounds were characterized by analytical and spectral (IR, H NMR, and LC-MS) Methods.


INTRODUCTION
The versatility of chalcone and its wide range of applicability in medicinal chemistry have attracted scientists all over the globe to concentrate their research around it. They consist of openchain flavonoids in which the two aromatic rings are joined by a three carbon chain [1]. Chalcones are natural biocides [2] and well known as intermediates for synthesizing of various heterocycles which have impressive array of biological activities; antibacterial [3], antiviral [4], antiinflammatory [5],antiulcerative [6],antimalarial [7], anticancer [8].In addition, benzofuran derivatives are nowadays an important class of organic compounds that occur in a great number of natural products [9].
The small nitrogen and oxygen containing molecules have been under investigation since long because of their important medicinal properties. 1,3,4-oxadiazole is commonly utilized pharmacophore has been subjected to extensive study in the recent years due to their metabolic profile and ability to engage in hydrogen bonding with receptor site. 1,3,4-Oxadiazoles are an important class of heterocyclic compounds with a wide range of biological activities such as antiviral [10], antimicrobial [11], antineoplastic [12], fungicidal [13], anticancer [14,15], inhibition of tyrosinase [16], They are also useful intermediates in organic synthesis [17] and widely employed as electron transporting and hole-blocking materials.

MATERIAL AND METHOD
Equipment's, Material and Physical measurements Melting points were determined in open capillary tubes and were uncorrected. The IR spectra were recorded by a Perkin-Elmer 237 spectrophotometer and 1H NMR was recorded in DMSO with TMS as internal standard on Bruker. AM 400 Mass spectra were recorded on M S route JMS 600-H.The completion reaction was monitored on TLC plates purchased from Merck (TLC silica gel 60 F 254 ) and all appropriate solvents were used as mobile phase. All the synthesized compounds were purified by recrystallization method. All the chemicals and solvents were A.R Grade and were used without further purification.
Step-3 Preparation for titled compounds (0.01mol)(E)-4-(3-(4-hydroxyphenyl)acryloyl)-5-methyl-2(p-tolyl)-1H-pyrazol-3(2H)-one-(II) dissolve in DMF. To this solution different derivative were added K 2 CO 3 (0.02mol) was added to the above mix Then it was allowed to stir for 4hr at room temp. The formation of titled intermediate was confirmed by observing the TLC using ethyl-acetate: hexane as a mobile phase. The completion of reaction was monitored using TLC plate.

ANTIMICROBIAL ACTIVITY
A broad panel of microbes was used for testing the antibacterial and antifungal properties of the molecules synthesized. The samples were tested by standard protocols like micro-dilution method. Anti-bacterial tests were carried against gram positive and gram negative bacteria. The anti-fungal tests were carried against two fungal strains C.alibicans and A.Niger.

SAR Study
It was observed that the use of ele.withdrawing and ele. Donating group to confer different electronic environments on the molecules showed a great impact on biological activity. Compound III 3 and III 6 showed good activity.

CONCLUSION
We have synthesized a verity of chalcone bearing 1,3,4-oxadiazole derivatives. In general, compounds with electron withdrawing group showed good anti-bacterial and anti-fungal activity. The results promoted the titled compound chalcone containing oxadiazole as an interesting lead for further synthetic and biological evolution. These titled compounds were confirmed by spectral data.