A Synthesis of Substituted 1,3,4-Oxadiazole, Pyrazole Deravatives and It’s Biological Activities

Aim: Nicotine Substituted 1,3,4 Oxadiazole and pyrazole moieties were integrated by utilizing hydrazide as halfway .Oxadiazole were acquired by two techniques one is by utilizing PoCl3 within the sight of fragrant corrosive ,other is by utilizing carbon disulphide in the presence ofpotassium hydroxide as an impetus .Pyrazoles were likewise gotten by ehtylacetoacetate we acquired unrefined item and again it was recrystallized by utilizing alcohol.All incorporated mixtures were evaluated for Antibacterial activity and enaminones showed promising action against standard medication ciprofloxacin. Methods: TLC on silica gel G was used to check for homogeneity of the title compound. H NMR, Mass, and IR Spectra were used to characterise these compounds, and their antibacterial activity Original Research Article D’souza et al.; JPRI, 33(37B): 260-269, 2021; Article no.JPRI.70412 261 was tested. Results: All of these compounds, including nicotine substituted ester, hydrazide, 1,3,4 Oxadiazole, and pyrazole, showed antibacterial activity. The maximum activity of enaminones was comparable to that of the standard drug ciprofloxacin (5mcg). Compound1 showed potent antimicrobial activity Conclusion: In the zone of inhibition studies, all six samples at MIC concentrations showed reasonable antimicrobial activity Compound1 showed very good antimicrobial activity


INTRODUCTION
Among the wide range of heterocycles Oxadiazole and pyrazole have been explored to develop new therapies [1][2][3][4][5][6][7]. Pyrazole and oxadiazole have attracted lot of attention to medical chemists. Wide spread use of Oxadiazole and pyrazole scaffolding a medical use .
According to the Web of Science data the scientific attention of 1,3,4-oxadiazoles application is continuously rising since the year 2000 . On the other hand, 1,2,5-oxadiazole derivatives found application mainly as High Energy Density Materials (HEDMs) as well as biologically active compounds with cytotoxic properties. Due to the instability and ring-opening of 1,2,3-oxadiazole heterocycle, resulting in substituted diazomethanes formation, this isomer of oxadiazole is least of all explored.
Importantly, the heterocycle demonstrates bioisosteric equivalence with ester and amide moieties due to the possibility of creation specific interaction (e.g., hydrogen bonding). It is a particularly useful alternative when the instability of those groups is observed (e.g., when the hydrolysis may appear) [10]. Nowadays, there are a few commercially available drugs containing 1,2,4-oxadiazole nucleus such as Oxolamine, Prenoxdiazine (cough suppressant) Butalamine (vasodilator), Fasiplon (nonbenzodiazepine anxiolytic drug, Pleconaril (antiviral drug), Ataluren (Duchenne muscular dystrophy treatment drug and Proxazole a drug used for functional gastrointestinal disorders. It is worth noting that 1,2,4-oxadiazole ring, as the only one of all oxadiazole isomers, occurs in the structures of natural products. For example, in 2011 Carbone M. et al. isolated two indole alkaloids Phidianidine A and Phidianidine B from sea slug Opisthobranch Phidiana militaris [11].
As a result, oxadiazole has a diverse set of biological properties, including antibacterial activity , [12] antifungal [13] antitumor [14] antitubercular , [14]  The same range of medicinal significance is associated with compounds containing pyrazole. This article is an attempt to synthesize five membered heterocycles by using hydrazide bridge.

MATERIALS AND METHODS
The open capillary method was used to determine the melting points, and the results are uncorrected. TLC on silica gel G was used to check for homogeneity of the compounds. Synthesized compounds were confirmed by 1HNMR, Mass and IR spectra.

General procedure Synthesis of Acid hydrazide
In a one pot three-component heterocyclo condensation process, ethyl 2-methyl-6-ethyl nicotinates was obtained via the reaction of Enaminons again it react with ethylene acetoacetate and ammonium acetate in refluxing acetic acid and it is achieved via the hydrazinolysis of ester derivatives with refluxing hydrazine hydrate. [17]  Synthesis of compound 4: A mixture of (0.01)acid hydroxide and (0.01) benzoic acid was dissolved in phosphorus oxide chloride and 18 to 22hrs . The reactive mixture was slowly poured onto crushed ice and stored all night. The separated solid mass was filtered, dried and purified by recrystallisation with ethanol. [18]  Synthesis of Compound 5: A mixture of 0.01 moles of nicotinic acid hydrazide , (0.01) (0.56 g) of potassium hydroxide and 10 ml of carbon disulphide were relaxed in 50 ml of 95% ethanol for 12 hr. The resulting mixture was concentrated and cooled to RT. Then it was acidified with Dil. Hcl. The solid mass, thus separated out was filtered, dried and purified by recrystallization from ethanol. [19]  Synthesis of Compound 6 A mixture of 0.01 moles of Nicotinic Acid hydroxide and 0.1 moles (13 ml) of ethylaceto acetate was heated in a water bath for 2 hours with stirring from time to time with a glass rod. The resultant heavy reddish syrup was allowed to cool to RT. It was washed thoroughly with ether to remove colored impurities. The separated solid has been filtered, dried and purified by recrystallization using ethanol. [20]

Determination of Melting Point
We utilized recrystallized Samples for the assurance of melting point by Guna apparatus. Firstly melting point Capillaries are loaded up with sample and kept inside a apparatus and noticed the liquefying point of the Sample .

 Evaluation of NMR Spectra
Predominantly NMR spectra is utilized to discover the kind of protons present in the sample .Here additionally we utilized recrystallized Sample and TMS is utilized as Reference cores and we dissolved the sample by DMSO and kept in the sample holder and spectra were recorded Instrument name :Bruker

 Evaluation of Mass Spectra
Usually mass spectra is used to recognize obscure mixtures in a sample , and to clarify the design and compound properties of various atoms.of the sample .Here we used crude product for the experiment .

Determination of minimum inhibitory concentration by tube dilution method
The antimicrobial activity of the compounds was promising. The compound minimum inhibitory concentrations were in the range of 12.5 to 50 mcg/ml. Compound 1 exhibited maximum activity with minimum inhibitory concentration (mic) of 12.5 mcg/ml as given in Table 1 and Fig. 1 remaining three compounds C2, C3 and C6 showed MIC at 25 mcg/ml The compounds C4 and C5 MIC was 50 mcg/ml. Compound1 was found to have potent antimicrobial activity.

Evaluation of antibacterial properties of the synthesized compounds were carried out against E. coli
In the zone of inhibition studies, all six samples at MIC concentrations showed antimicrobial activity. The maximum activity of compound 1 was comparable to that of the standard drug ciprofloxacin (5mcg).zone of inhibition was found to be 31.01±0.034 for compound one with was potent as compared to standard ciprofloxacin 32 mm ±0.044.
So from this result compound C1 is having potent antibacterial activity.

DISCUSSION
Utilizing corrosive hydrazide as a halfway, a progression of mixtures were integrated, including oxadiazole and pyrazole subsidiaries, and these mixtures were affirmed by its Dissolving point and by portrayed upsides of NMR. Compound

CONCLUSION
In the zone of inhibition studies, all six samples at MIC concentrations showed reasonable antimicrobial activity Compound1 showed very good antimicrobial activity

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.