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1、ENCLOSURE-I6. BRIEF RESUME OF THE INTENDED WORK:6.1: Need for the study: Research particularly drug discovery is a continuous process for many reasons like:a. The development of resistance of drug therapy continues to stimulate the search for more effective agents.b. Though some of the drugs are hig
2、hly effective and they are associated with side effects.c. Some drugs are allergic to some persons.d. Nature always posses problem to human races through newer diseases. Hence man is always in search of newer, safer and more potent drugs than the existing ones. Thus the drug discovery is a newer end
3、ing process, hence is the present investigation. There is a better understanding of the kinetics, or factors that affect the kinetics, of the different forms of PLA2. New forms of PLA2 are being discovered, such as the cPLA2, which fit the role of an intracellularly regulated enzyme. Multiple forms
4、of PLA2 tend to complicate the elucidation of the cellular mechanisms that regulate AA release and the subsequent eicosanoid production. Because of the factors that affect PLA2 kinetics and the unknown nature of the PLA2 that regulates AA release. 10This review discussed selected classes of inhibito
5、rs because these have generated the most intense research in the field. There is a multitude of structurally diverse compounds reported in the literature that have been reported to be inhibitors of PLA2 in vitro and some have been reported to have anti-inflammatory activity. It is clear from a brief
6、 survey of the literature that the bulk of PLA2 inhibitors have topical anti-inflammatory activity. This may be due to the nature of these inhibitors: because they are hydrophobic they may be more readily absorbed in the skin whereas when given orally they may not be absorbed. To data, manoalide has
7、 been clinically evaluated in man and a new Bristol-Myers Squibb retenoid derivative may enter clinical trials for psoriasis; however, there are no PLA2 inhibitors on the market or significantly advanced in clinical development.This indicates the lack of understanding of this enzyme for the developm
8、ent of relevant inhibitors, which is related to the lack of understanding of the relevant PLA2 that regulates AA release and eicosanoid biosynthesis. The concept of regulation of eicosanoid biosynthesis by PLA2 inhibition and decreased AA availability still remains a viable therapeutic approach for
9、the treatment of inflammatory diseases. The proof of this concept has not been obtained because of the complex nature of PLA2 and the multiple forms of PLA2 in the cell. Clinical results with cyclooxygenase inhibitors and recent clinical results with inhibitor of 5-lipoxygenase demonstrate that if i
10、nhibition of PLA2 results in reduction in both lipid mediators, a good anti-inflammatory compound should result. ENCLOSURE-II6.2: Review of literature: Literature survey revealed that pyrazoles have received considerable attention during last three decades as they are endowed with variety of biologi
11、cal activities and has wide range of therapeutic activities.Most of the pyrazole derivatives are reported to posses wide range of therapeutic activities.Deshmukh MB et al1 synthesized Pyrazoles derivatives posses wide range of biological activities such as antibacterial, antifungal and antiinfammato
12、ry.Singh SP et al2. Synthesized 4, 5-Bipyrazoles as antibacterial and anti-inflammatory activity.Rajeev Jain et al3. Synthesized Sulphonamoylazopyrazoles as antibacterial activity. Salem A Basaif et al4 synthesized new di and tri substituted pyrazoles as antiinflammatory, antibacterial, antineoplast
13、ic, antiallergics, and hypoglycemic activities.Garaje AS et al5 synthesized 1-(3, 5, 6-Trichloro-pyridyl-2-actyloxy)-2,4-dimethyl pyrazole as antimicrobial activity.Sonar6 VN synthesized pyrazolylindoles as potent anti-inflammatory activity.Palker R.B. et al7 synthesized 3,5-diarylpyrazoles as poten
14、t antimicrobial activity.Mohd.Amir et al8 synthesized 1-(substituted)-3,5-diphenyl-4-(arylazo)-pyrazoles as antimicrobial activity.Faidallah H.M. et al9 synthesized new pyrazoles chalcones as anti-inflammatory, analgesic, antibacterial, hypoglycemic activities.Thakare N.R. et al10 ynthesized 3-(4-me
15、thyl-7-hydroxy-8-coumarinyl)-5- arylpyrazoles as various activities.Mogilaiah K. et al11 synthesized, 8-Naphthyridinylpyrazolo3,4-c Pyrazoles are having various activities.Brijesh Kumar N. Singh12 synthesized4-(2H-1,2,3-Triazole)phenylazo-4-yl-1-substituted-3,5-dimethylpyrazole as various activity.S
16、olanki PR. et al13 synthesized semi-substituted pyrazoles eg. 3-(2- Hydroxy phenyl)-5-methyl pyrazole and 1-Phenyl-3-(2-hydroxyphenyl)-5-methyl pyrazole as anti-inflammatory, antibacterials, antitubercular, antiviral, and antifungal activities.El-Saied A Aly et al14synthesized some novel pyrazole derivatives as va
