BIOLOGICAL ACTIVITIES OF ACTH-ANALOGUES VARIED IN THE ACTIVE SITE

1977 ◽  
Vol 84 (3) ◽  
pp. 470-484 ◽  
Author(s):  
Johannes W. van Nispen ◽  
Godefridus I. Tesser ◽  
Pierre L. Barthe ◽  
René Maier ◽  
Lotte Schenkel-Hulliger
Keyword(s):  
Electron Donor ◽  
Active Site ◽  
Lipolytic Activity ◽  
Biological Activities ◽  
Partial Agonists ◽  
Acth Analogues ◽  
Low Activity

ABSTRACT The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold.

Novel Piperazine Amides of Cinnamic Acid Derivatives as Tyrosinase Inhibitors

2018 ◽  
Vol 16 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Zehra Tuğçe Gür ◽  
Fatma Sezer Şenol ◽  
Suhaib Shekfeh ◽  
İlkay Erdoğan Orhan ◽  
Erden Banoğlu ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Active Site ◽  
Agaricus Bisporus ◽  
Biological Activities ◽  
Docking Simulation ◽  
Cinnamic Acid Derivatives ◽  
In Silico Docking ◽  
Amide Derivatives ◽  
Tyrosinase Inhibitors ◽  
Further Development

Background: A series of novel cinnamic acid piperazine amide derivatives has been designed and synthesized, and their biological activities were also evaluated as potential tyrosinase inhibitors. Methods: Compounds 9, 11 and 17 showed the most potent biological activity (IC50 = 66.5, 61.1 and 66 µM, respectively). In silico docking simulation was performed to position compound 11 into the Agaricus bisporus mushroom tyrosinase’s active site to determine the putative binding interactions. Results and Conclusion: The results indicated that compound 11 could serve as a promising lead compound for further development of potent tyrosinase inhibitors.

scholarly journals Novel silver(I) compounds with 1-adamantanamine

2018 ◽  
Vol 83 (6) ◽  
pp. 699-705 ◽  
Author(s):  
Dejan Jeremic ◽  
Milena Djordjevic ◽  
Srdjan Miletic ◽  
Ljubica Andjelkovic ◽  
Dusan Sladic ◽  
...  
Keyword(s):  
Electron Donor ◽  
Aliphatic Amine ◽  
Biological Activities ◽  
Spectroscopic Characterization ◽  
Antibacterial Activities ◽  
Monodentate Ligand ◽  
Donor Ligand ◽  
Minimum Inhibitory Concentrations ◽  
New Compounds

In this work, three novel silver(I) complexes with an almost completely rigid and bulky monodentate ligand, 1-adamantanamine, were synthesized. The aliphatic amine, 1-adamantanamine, is the sole electron donor ligand in these complexes. In addition to spectroscopic characterization, the basic biological activities of the new compounds were investigated and their minimum inhibitory concentrations were determined. The antifungal and antibacterial activities indicate that these compounds could potentially be applied as new therapeutics.

scholarly journals Crystal Structure of Thrombin in a Self-inhibited Conformation

2006 ◽  
Vol 281 (43) ◽  
pp. 32922-32928 ◽  
Author(s):  
Agustin O. Pineda ◽  
Zhi-Wei Chen ◽  
Alaji Bah ◽  
Laura C. Garvey ◽  
F. Scott Mathews ◽  
...  
Keyword(s):  
Single Molecule ◽  
Active Site ◽  
Protein C ◽  
Conformational Transition ◽  
Guanidinium Group ◽  
Hydrolysis Of ◽  
Packing Interactions ◽  
Low Activity ◽  
Resolution Structure ◽  
Primary Specificity

The activating effect of Na+ on thrombin is allosteric and depends on the conformational transition from a low activity Na+-free (slow) form to a high activity Na+-bound (fast) form. The structures of these active forms have been solved. Recent structures of thrombin obtained in the absence of Na+ have also documented inactive conformations that presumably exist in equilibrium with the active slow form. The validity of these inactive slow form structures, however, is called into question by the presence of packing interactions involving the Na+ site and the active site regions. Here, we report a 1.87Å resolution structure of thrombin in the absence of inhibitors and salts with a single molecule in the asymmetric unit and devoid of significant packing interactions in regions involved in the allosteric slow → fast transition. The structure shows an unprecedented self-inhibited conformation where Trp-215 and Arg-221a relocate >10Å to occlude the active site and the primary specificity pocket, and the guanidinium group of Arg-187 penetrates the protein core to fill the empty Na+-binding site. The extreme mobility of Trp-215 was investigated further with the W215P mutation. Remarkably, the mutation significantly compromises cleavage of the anticoagulant protein C but has no effect on the hydrolysis of fibrinogen and PAR1. These findings demonstrate that thrombin may assume an inactive conformation in the absence of Na+ and that its procoagulant and anticoagulant activities are closely linked to the mobility of residue 215.

scholarly journals Biological activities (antioxidant and antimicrobial activity) of the aqueous extracts and essential oil of Ammoides verticillata (Nounkha)

2018 ◽  
Vol 75 (2) ◽  
pp. 64
Author(s):  
Ramdane MOHAMED SAID ◽  
Nabahat BENMANSOUR
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oil ◽  
Biological Activities ◽  
Stable Free Radical ◽  
E Coli ◽  
Highly Sensitive ◽  
Clinical Action ◽  
Ammoides Verticillata ◽  
Antioxidant And Antimicrobial Activity ◽  
Low Activity

The phytochemical review conducted on the aerial part Ammoides verticillata has revealed the presence of six chemical families: flavonoids, tannins; gallic tannins, anthocyanins and the coumarins, cateichic tannins. The aqueous extract of the Ammoides verticillata could bring back the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) to the yellow-colored diphenylpicrylhydrazine with an IC50 of 0.020 mg.mL-1. It is gifted with antioxidant activity, however it was less effective than vitamin C (0.001 mL-1). The essential oil of the Ammoides verticillata has presented a strong antimicrobial activity against Gram negatif germs targets of original clinical action: E. coli (ESBL) (37 mm), E. coli (39.5 mm), Klebsiella pneumoniae (36.5 mm) and especially with the yeast: Candida albicans ATCC 10231 (47 mm) and Saccharomyces cerevisie ATCC (42 mm), which are highly sensitive to the oil inhibitory action. However, the oil has presented a low activity against the bacteria P. aeruginosa (12.5 mm).

Synthesis of novel NSAIDs linked to triazolyl-oxadiazole heterocyclic compounds as more comprehensive antimicrobial agents: A computational molecular docking

2021 ◽  
Vol 17 ◽  
Author(s):  
Shaik Adamshafi ◽  
Venkatarao Veera ◽  
Mohan Rao SVM ◽  
Kishore Pilli VVN
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Solubility Parameters ◽  
Diffusion Method ◽  
Binding Interaction ◽  
Protein Database ◽  
Chemical Structures

Introduction: Progress in the development of triazolyl-oxadiazoles is a bisphosphonate-700 inhibitor is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non steroidal anti-inflammatory drugs in a combined form and evaluated for their antibacterial, antifungal activities, docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial, antifungal activity of these compounds was screened against Gram-positive, Gram-negative bacteria and fungal stains by agar well diffusion method. The crystal structure of S. aureus complexed with active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug likeness score, lipophilicity and solubility parameters by Molinspiration and Molsoft software. 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2) Results: Among the synthesised NSAID-triazolyl-oxadiazole containing 2-nitro-5-methoxy (7f), 3,4-dichloro (7g) derivatives were found to be high active antibacterial agents against S. aureus, E. coli with MICs 16, 19 μg/mL respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger and MICs 56, 76, 130 μg/mL respectively. From molecular docking NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A˚), Arg45 (2.17 A˚), Lys17, Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug likeness model score 0.49, 0.41 was found for compounds 7h, 7b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug like properties and are expected to present good bioavailability profile. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guide lines that could aid in further development of these derivatives.

Sulfur-Substituted α-Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors:  Biological Activities, CoMFA Analysis, and Active Site Modeling

2005 ◽  
Vol 48 (7) ◽  
pp. 2407-2419 ◽  
Author(s):  
Alejandra Gallardo-Godoy ◽  
Angélica Fierro ◽  
Thomas H. McLean ◽  
Mariano Castillo ◽  
Bruce K. Cassels ◽  
...  
Keyword(s):  
Active Site ◽  
Biological Activities ◽  
Mao A

scholarly journals Structure ofEscherichia coliGrx2 in complex with glutathione: a dual-function hybrid of glutaredoxin and glutathioneS-transferase

2014 ◽  
Vol 70 (7) ◽  
pp. 1907-1913 ◽  
Author(s):  
Jun Ye ◽  
S. Venkadesh Nadar ◽  
Jiaojiao Li ◽  
Barry P. Rosen
Keyword(s):  
Escherichia Coli ◽  
Electron Donor ◽  
Active Site ◽  
Active Sites ◽  
Catalytic Cycle ◽  
Dual Function ◽  
Active Site Residues ◽  
E Coli ◽  
Arsenate Reduction ◽  
Gst Activity

The structure of glutaredoxin 2 (Grx2) fromEscherichia colico-crystallized with glutathione (GSH) was solved at 1.60 Å resolution. The structure of a mutant with the active-site residues Cys9 and Cys12 changed to serine crystallized in the absence of glutathione was solved to 2.4 Å resolution. Grx2 has an N-terminal domain characteristic of glutaredoxins, and the overall structure is congruent with the structure of glutathioneS-transferases (GSTs). Purified Grx2 exhibited GST activity. Grx2, which is the physiological electron donor for arsenate reduction byE. coliArsC, was docked with ArsC. The docked structure could be fitted with GSH bridging the active sites of the two proteins. It is proposed that Grx2 is a novel Grx/GST hybrid that functions in two steps of the ArsC catalytic cycle: as a GST it catalyzes glutathionylation of the ArsC–As(V) intermediate and as a glutaredoxin it catalyzes deglutathionylation of the ArsC–As(III)–SG intermediate.

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