scholarly journals Inactivation of cysteine proteases by peptidyl epoxides: characterization of the alkylation sites on the enzyme and the inactivator

2000 ◽  
Vol 346 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Amnon ALBECK ◽  
Sharon KLIPER
Keyword(s):  
Model Compound ◽  
Hydrolysis Product ◽  
Cysteine Proteases ◽  
Cysteine Residue ◽  
High Resolution Mass Spectrum ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
13C Nmr Analysis ◽  
Unique Signal

Erythro peptidyl epoxides are selective inactivators of cysteine proteases. The alkylation site, both on the enzyme papain and on the epoxide itself, was characterized. The inactivation of papain with the peptidyl epoxide erythro benzyloxycarbonyl-Phe-Ala-epoxide was followed by total hydrolysis by acid. Mass spectral analysis of the hydrolysate revealed, in addition to the expected amino acids, a unique signal of m/z 209 (MH+). Its high-resolution mass spectrum and daughter peak analysis correspond to the product of alkylation on cysteine and the expected fragmentation. A similar MS pattern was obtained for a synthetic model compound corresponding to the expected hydrolysis product. A 13C NMR analysis of papain inactivated by a specifically 13C-labelled peptidyl epoxide indicated that the alkylation of the enzyme's cysteine residue occurs on the primary carbon of the epoxide moiety.

scholarly journals A Convergent Approach for the Synthesis of New Pyrazolyl Bipyridinyl Substituted Coumarin Derivatives as Antimicrobials

2014 ◽  
Vol 40 ◽  
pp. 1-16 ◽  
Author(s):  
Varun G. Bhila ◽  
Yogita L. Chovatiya ◽  
Chirag V. Patel ◽  
Rakesh R. Giri ◽  
Dinkar I. Brahmbhatt
Keyword(s):  
Antimicrobial Activity ◽  
Coumarin Derivatives ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
H Nmr ◽  
Convergent Approach ◽  
C Nmr ◽  
Substituted Coumarins

Some new 3-[3-(1-phenyl-3-aryl-1H-pyrazol-4-yl) acryloyl] coumarins 3a-f were synthesized (coumarin chalcones) by the condensation of various 3-acetyl coumarins 1 and appropriate 1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 2. These coumarin chalcones 3a-f were then employed for the synthesis of pyrazolyl bipyridinyl substituted coumarins 7a-f, 8a-f, and 9a-f under Krohnke’s reaction condition. The characterization of all the synthesized compounds was carried out by elemental analysis, IR, 1H-NMR, 13C-NMR, DEPT-135 and mass spectral analysis. In addition to that, in vitro antimicrobial competency of the title compounds was assessed against selected pathogens. Compounds 3b, 3e, 7b, 8b, 8c and 9b exhibited excellent antimicrobial activity and said to be the most proficient members of the series.

scholarly journals Synthesis and characterization of some chalcones and their cyclohexenone derivatives

2010 ◽  
Vol 8 (1) ◽  
pp. 174-181 ◽  
Author(s):  
Thekke Sreevidya ◽  
Badiadka Narayana ◽  
Hemmige Yathirajan
Keyword(s):  
Spectral Analysis ◽  
Ethyl Acetoacetate ◽  
Aldol Condensation ◽  
Synthesis And Characterization ◽  
Mass Spectral Analysis ◽  
X Ray ◽  
Mass Spectral ◽  
Aryl Aldehydes ◽  
Cyclohexenone Derivatives

AbstractA series of chalcones and their derivatives have been synthesized. Chalcones, 1-(1,3-benzodioxol-5-yl)-3-(aryl)-prop-2-en-1-ones were prepared by the aldol condensation of 1-(1,3-benzodioxol-5-yl)ethanones and aryl aldehydes. Based-catalyzed condensation of 1-(1,3-benzodioxol-5-yl)-3-(aryl)prop-2-en-1-ones with ethyl acetoacetate yields corresponding ethyl 4-(1,3-benzodioxol-5-yl)-6-(aryl)-2-oxocyclohex-3-ene-1-carboxylates. Some of the synthesized chalcones were reported in the literature; the newly synthesized compounds were characterized by single crystal X-ray studies, IR, 1H-NMR and LCMS mass spectral analysis.

scholarly journals 3-(3,5-Difluorophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde

2018 ◽  
Author(s):  
Naveen Kumar ◽  
Swamy Sreenivasa ◽  
Vasantha Kumar ◽  
Nadigar Revansiddappa Mohan
Keyword(s):  
Spectral Analysis ◽  
13C Nmr ◽  
Title Compound ◽  
Structure Characterization ◽  
Dimethyl Formamide ◽  
The Novel ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
Phosphorous Oxychloride

Vilsmeier–Haack reaction of (E)-1-(1-(3,5-difluorophenyl)ethylidene)-2-phenylhydrazine (1) using dimethyl formamide in excess of phosphorous oxychloride by conventional method, resulted in the synthesis of title compound 3-(3,5-difluorophenyl)-1-phenyl-1H-pyrazole-4- carbaldehyde (2) in good yield and high purity. Structure characterization of the novel title compound was done by IR, 1H NMR, 13C NMR and mass spectral analysis.

scholarly journals Preparation and Characterization of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for their Anti-Inflammatory Activity

2021 ◽  
pp. 992-1004
Author(s):  
Jitendra Kumar Chaudhary ◽  
Alok Pal Jain ◽  
O. P. Tiwari
Keyword(s):  
Inflammatory Activity ◽  
Paw Edema ◽  
Mass Spectral Analysis ◽  
Phenyl Hydrazine ◽  
Design Synthesis ◽  
Standard Drug ◽  
Mass Spectral ◽  
Anti Inflammatory ◽  
Relevant Degree

The objective of the paper was to design, synthesis and characterization of new 1,3,5-trisubstituted-2-pyrazolines derivative and evaluate for anti-inflammatory potential. The 1,3,5-tri-substituted-2-pyrazolines derivatives has been synthesized by the reaction of chalcone     derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride. Total Sixteen compounds has been synthesized and characterized by the IR, 1HNMR and mass spectral analysis. Proposed compounds have been evaluated for anti-inflammatory activity. Anti-inflammatory activity of the compounds carried out by two animal     model i.e. Carrageenan induced, paw edema in rats and Inhibition of formalin induced paw edema in rats. Anti-inflammatory activity of the compounds C7, C8 and C2 were shown 98.26,  92.77 and 96.24 percentages of inhibition and compounds D7, D8 and D2  were shown 81.50, 83.81 and 78.32 percentages of inhibition as compared to the standard drug Diclofenac at 10 mg/kg was inhibit the inflammation 99.42 % after 6h. These result is a evident that synthesized compounds show relevant degree of anti-inflammatory activity as compared to the standard drug. It is also concluded that the presence of SO2NH2 group, Cl, CH3, OCH3 and N(CH3)2 group may provide the active compounds when attached to the pyrazoline group. But the addition of OH, Br and no substitution in phenyl ring may diminish the activity. 

scholarly journals Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B

2021 ◽  
Vol 22 (5) ◽  
pp. 2501
Author(s):  
Sonja Hinz ◽  
Dominik Jung ◽  
Dorota Hauert ◽  
Hagen S. Bachmann
Keyword(s):  
Protein Function ◽  
Tumor Development ◽  
Cysteine Residue ◽  
Type I ◽  
Pharmacological Characterization ◽  
Anti Cancer ◽  
And Function ◽  
Caax Motif ◽  
Important Drug

Geranylgeranyltransferase type-I (GGTase-I) represents an important drug target since it contributes to the function of many proteins that are involved in tumor development and metastasis. This led to the development of GGTase-I inhibitors as anti-cancer drugs blocking the protein function and membrane association of e.g., Rap subfamilies that are involved in cell differentiation and cell growth. In the present study, we developed a new NanoBiT assay to monitor the interaction of human GGTase-I and its substrate Rap1B. Different Rap1B prenylation-deficient mutants (C181G, C181S, and ΔCQLL) were designed and investigated for their interaction with GGTase-I. While the Rap1B mutants C181G and C181S still exhibited interaction with human GGTase-I, mutant ΔCQLL, lacking the entire CAAX motif (defined by a cysteine residue, two aliphatic residues, and the C-terminal residue), showed reduced interaction. Moreover, a specific, peptidomimetic and competitive CAAX inhibitor was able to block the interaction of Rap1B with GGTase-I. Furthermore, activation of both Gαs-coupled human adenosine receptors, A2A (A2AAR) and A2B (A2BAR), increased the interaction between GGTase-I and Rap1B, probably representing a way to modulate prenylation and function of Rap1B. Thus, A2AAR and A2BAR antagonists might be promising candidates for therapeutic intervention for different types of cancer that overexpress Rap1B. Finally, the NanoBiT assay provides a tool to investigate the pharmacology of GGTase-I inhibitors.

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