Design, Synthesis, Characterization and Biological Evaluation of Pyrazole Derivatives

Nandhini, R (2021) Design, Synthesis, Characterization and Biological Evaluation of Pyrazole Derivatives. Masters thesis, Nandha College of Pharmacy, Erode.


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The pyrazole moiety is found as an integral structural unit in a variety of pharmacologically and agrochemically significant chemicals. The anti-inflammatory (celecoxib), anti-obesity (rimonabant), analgesic (difenamizole), antipsychotic (CDPPB), H2-receptor agonist (betazole) and antidepressant (fezolamide activities of pyrazole-based drugs have demonstrated their pharmacological importance. Various synthetic methodologies have been devised as a result of the above-mentioned advantages of pyrazole-based compounds. The synthetic work was conducted under appropriate experimental conditions and the expected compounds had been obtained. The biological studies were carried out to observe the effect of substituents on the antimicrobial and anti-diabetic activities. From the outcomes of antimicrobial and anti-diabetic studies, it is concluded that, the present study describe the synthesis and characterization of heterocyclic frameworks. The derivatives of pyrazole compound were synthesized by two steps, in first step synthesis of 1, 3 diketone derivatives from substituted aniline and diethylmalonate in presence of concentrated sulphuric acid and sodium nitrite. The next step, synthesis pyrazole derivatives from 1, 3 diketone react with distinct phenyl hydrazines like phenyl hydrazine HCl, 2, 4-dinitro phenyl hydrazine in presence pyridine as a catalyst with reflux which is confirmed by TLC in both step 1 and step 2 by using the mobile phase chloroform: methanol (9.5:0.5). Further the synthesized compound was satisfied by its melting point, λmax value. The obtained melting point range between 105-165°C by using open capillary method and λmax values shows the range between 200-400 nm. The above characteristic data’s attached in table-2. Synthesized pyrazole derivatives were spectral characterized by Infra-red, Proton NMR and Mass spectroscopy. In Infra-red spectroscopy should indicates the absence of C=O (1750-1725 cm-1). Simultaneously the formation (C=N) stretch (1600-1480 cm-1) should present in the data. Compound A1, A2, C1 and C2 was confirmed by its IR spectral analysis, which indicates the value of 2656, 2512, 2954, 2634 cm-1 corresponding to the O-H group of carboxylic acid and another absorption band of compound A2, B2 and C2 was satisfied 1333, 1330 and 1333 cm-1 corresponding to the N=O group. Compound C1 and C2 was confirmed by 1163, 1142 cm-1 corresponding to the S=O stretch of Sulphanilic acid. Another analysis of 1HNMR spectrum shows the signals observed at δ 10-12 ppm indicates O-H proton signal and δ 2.5 ppm indicates the Sulphanilic acid O-H proton signal, in addition δ 7.6-8.5 ppm indicates the aromatic C-H proton signals. Molecular mass of synthesized pyrazole compounds by its Mass spectral analysis, which is indicated that the molecular ion peaks at 380, 470, 415, 506, 380 and 470. The docking studies with the pyrazole derivatives showed better binding score than the standard drug and our finding compounds will help in selecting of in vivo biological screening. The three compounds (A1, A2 and C2) were gave a better binding affinity and interaction with the active site residues of the enzymes. Docking results of reported pyrazole molecules and their binding interactions with residues within 3Å radius were found out to understand the specific type of binding interactions of molecular features of pyrazole compounds. Binding energy values obtained after docking study was compared with anti-diabetic activity of each of reported reference pyrazole compounds. Binding energy of potent pyrazoles was found to be correlated. There by crucial residues of binding interaction among the potent reported pyrazole compounds were identified. The presence or absence of these crucial residues was observed in docking study of novel pyrazole compounds. The present study aimed at a recent update made on novel methodologies adopted in the synthesis of pyrazole derivatives with emphasis on anti-bacterial activity. Pyrazole is one of the major tools to be investigated in drug design and discovery. Many studies have been reported by researches that have claimed the significant biological potential of these derivatives. However, numerous studies on pyrazole compounds shown to exhibit potential antifungal and anti-bacterial activities. Additionally, some important patents granted to this heterocyclic nucleus related to antimicrobial potential are also addressed appropriately. The anti-bacterial activity of the synthesized pyrazole derivatives was performed by agar well diffusion method using different strains of gram positive and gram negative bacteria. The pyrazole have good anti-bacterial activity. The synthesized pyrazole derivatives are compound A1, A2, B1, B2, C1 and C2 had undergone to the anti-bacterial study against Bacillus subtilis, Staphylococcus aureus, Serratia marcescens, Escherichia Coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Proteus vulgaris. The compound A1, A2, B2 and C2 shows better inhibition against both gram positive and gram negative bacteria. Because of its having electron withdrawing group presence. The compound C1 and B1 shows good inhibition against gram negative bacteria. The present investigation of our study, the effect of the synthesized compound for its anti-diabetic activity has done and results were summarized in table-5. Compound C2 have more significant in anti-diabetic activity, due to the presence of nitro group. Compound A1 and A2 moderate significant anti-diabetic activity. In in vitro study A2 having a highest binding energy than standard Glibenclamide drug. But the in vivo results slightly differ from in vitro study. Hopefully, these findings will prove helpful to medicinal chemists for the development of new binding affinity of enzymes related to Type II diabetes. Pyrazoles are an important class of compounds for new drug development that attracted much attention. Several pyrazole derivatives have been synthesized as target structures and evaluated for their biological activities. More investigations must be carried out to evaluate more activities of pyrazole for many diseases whose treatment are difficult in the medical sciences.

Item Type: Thesis (Masters)
Additional Information: 261915403
Uncontrolled Keywords: Design, Synthesis, Characterization, Biological Evaluation, Pyrazole Derivatives.
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Subramani R
Date Deposited: 02 Nov 2022 17:40
Last Modified: 03 Nov 2022 14:03

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