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

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.

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.

scholarly journals Activity Prediction of Bioactive Compounds Contained in Etlingera elatior Against the SARS-CoV-2 Main Protease: An In Silico Approach

2020 ◽  
Vol 3 (4) ◽  
pp. 235-242
Author(s):  
Dwi Syah Fitra Ramadhan ◽  
Taufik Muhammad Fakih ◽  
Arfan Arfan
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Biological Activities ◽  
Activity Prediction ◽  
Ergosterol Peroxide ◽  
Main Protease ◽  
Promising Therapeutic Target ◽  
In Silico Methods ◽  
Etlingera Elatior

The COVID-19 pandemic has become a serious problem today, with its prevalence increasing every day. The SARS-CoV-2 main protease (MPro) is a promising therapeutic target to inhibit replicating and spreading the virus that causes COVID-19. The compounds contained in the Etlingera elatior plant has the potential. This study aimed to examine the compounds' activity in E. elatior against SARS-CoV-2 MPro using in silico methods. A total of seven compounds contained in E. elatior were obtained from the Knapsack database. The compounds were then docked into the SARS-CoV-2 MPro receptor's active site with the PDB ID 6LU7. Afterward, the biological activities were predicted by the PASS prediction webserver. The molecular docking results showed that ergosterol peroxide and sitostenone had the best binding energy with -10.40 kcal/mol and -9.17 kcal/mol, respectively. The in silico PASS prediction showed it has potential as antiviral therapy. It concluded ergosterol peroxide and sitostenone has the potential as SARS-CoV-2 MPro inhibitor candidate.

scholarly journals Multi-state structure determination and dynamics analysis reveals a new ubiquitin-recognition mechanism in yeast ubiquitin C-terminal hydrolase

2021 ◽  
Author(s):  
Mayu Okada ◽  
Yutaka Tateishi ◽  
Eri Nojiri ◽  
Tsutomu Mikawa ◽  
Sundaresan Rajesh ◽  
...  
Keyword(s):  
Structure Determination ◽  
Active Site ◽  
Residual Dipolar Couplings ◽  
Biological Activities ◽  
Protein Structure Determination ◽  
Paramagnetic Nmr ◽  
Structural Basis ◽  
Recognition Mechanism ◽  
N Terminus ◽  
Large Motion

Despite accumulating evidence that protein dynamics is indispensable for understanding the structural basis of biological activities, it remains challenging to visualize the spatial description of the dynamics and to associate transient conformations with their molecular functions. We have developed a new NMR protein structure determination method for the inference of multi-state conformations using multiple types of NMR data, including paramagnetic NMR and residual dipolar couplings, as well as conventional NOEs. Integration of these data in the structure calculation permits delineating accurate ensemble structures of biomacromolecules. Applying the method to the protein yeast ubiquitin hydrolase 1 (YUH1), we find large dynamics of its N-terminus and crossover loop surrounding the active site for ubiquitin-recognition and proteolysis. The N-terminus gets into and out of the crossover loop, suggesting their underlying functional significance. Our results, including those from biochemical analysis, show that large motion surrounding the active site contributes strongly to the efficiency of the enzymatic activity.

scholarly journals An active site tyrosine residue is essential for amidohydrolase but not for esterase activity of a class 2 histone deacetylase-like bacterial enzyme

2007 ◽  
Vol 401 (3) ◽  
pp. 659-665 ◽  
Author(s):  
Kristin Moreth ◽  
Daniel Riester ◽  
Christian Hildmann ◽  
René Hempel ◽  
Dennis Wegener ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Active Site ◽  
Esterase Activity ◽  
Histone Deacetylases ◽  
Biological Activities ◽  
Hdac Inhibitors ◽  
Porcine Liver ◽  
Drug Candidates ◽  
Core Histones ◽  
Ic50 Values

HDACs (histone deacetylases) are considered to be among the most important enzymes that regulate gene expression in eukaryotic cells acting through deacetylation of ϵ-acetyl-lysine residues within the N-terminal tail of core histones. In addition, both eukaryotic HDACs as well as their bacterial counterparts were reported to also act on non-histone targets. However, we are still far from a comprehensive understanding of the biological activities of this ancient class of enzymes. In the present paper, we studied in more detail the esterase activity of HDACs, focussing on the HDAH (histone deacetylase-like amidohydrolase) from Bordetella/Alcaligenes strain FB188. This enzyme was classified as a class 2 HDAC based on sequence comparison as well as functional data. Using chromogenic and fluorogenic ester substrates we show that HDACs such as FB188 HDAH indeed have esterase activity that is comparable with those of known esterases. Similar results were obtained for human HDAC1, 3 and 8. Standard HDAC inhibitors were able to block both activities with similar IC50 values. Interestingly, HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA) also showed inhibitory activity against porcine liver esterase and Pseudomonas fluorescens lipase. The esterase and the amidohydrolase activity of FB188 HDAH both appear to have the same substrate specificity concerning the acyl moiety. Interestingly, a Y312F mutation in the active site of HDAH obstructed amidohydrolase activity but significantly improved esterase activity, indicating subtle differences in the mechanism of both catalytic activities. Our results suggest that, in principle, HDACs may have other biological roles besides acting as protein deacetylases. Furthermore, data on HDAC inhibitors affecting known esterases indicate that these molecules, which are currently among the most promising drug candidates in cancer therapy, may have a broader target profile requiring further exploration.

Synthesis, Structure Elucidation and Biological Activities of Some Novel 4(3H)-Quinazolinones as Anti-Biofilm Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 313-321
Author(s):  
Sevda Türk ◽  
Sevgi Karakuş ◽  
Abdulilah Ece ◽  
Seyhan Ulusoy ◽  
Gülgün Bosgelmez-Tınaz
Keyword(s):  
Active Site ◽  
Biofilm Formation ◽  
Structure Elucidation ◽  
Biological Activities ◽  
Opportunistic Pathogen ◽  
Docking Studies ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Inhibitory Activities ◽  
Clinically Significant

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic infections in immunocompromised patients. The inhibition of Quorum Sensing (QS) system has been recognized as an attractive strategy for the treatment of P. aeruginosa infections. In the present study, a series of novel 2-methyl-3-[4-(substituedaminosulfonyl)phenyl]-4(3H)-quinazolinones (1-8) were synthesized and tested for their biofilm formation and swarming motility inhibitory activities in P. aeruginosa PA01. </P><P> Findings: These compounds were found to reduce biofilm formation by 20-32% and swarming motility by 51-62% in P. aeruginosa PA01 at a concentration of 12.5&#181;M. Molecular docking studies were also performed to elucidate the possible key interactions of these compounds with the active site of the P. aeruginosa QS receptor LasR. Furthermore, some molecular properties related to drug likeness and ADME were predicted. </P><P> Results and Conclusion: Results of this study demonstrated that compounds 1-8 can influence QS-regulated biofilm formation and swarming motility in P. aeruginosa PA01 by binding LasR protein and could be developed as anti-biofilm agents to treat chronic biofilm associated infections caused by P. aeruginosa and other clinically significant pathogens.

[3H]HARMALINE AS A SPECIFIC LIGAND OF MAO A?I. PROPERTIES OF THE ACTIVE SITE OF MAO A FROM RAT AND BOVINE BRAINS

1979 ◽  
Vol 32 (6) ◽  
pp. 1817-1827 ◽  
Author(s):  
D. L. Nelson ◽  
A. Herbet ◽  
Y. Pétillot ◽  
L. Pichat ◽  
J. Glowinski ◽  
...  
Keyword(s):  
Active Site ◽  
Mao A ◽  
Specific Ligand

scholarly journals Preparation and Biological Activities of a Bivalent Poly(Ethylene Glycol) Hybrid Containing an Active Site and Its Synergistic Site of Fibronectin

2002 ◽  
Vol 50 (9) ◽  
pp. 1229-1229 ◽  
Author(s):  
Yuichi Susuki ◽  
Keiko Hojo ◽  
Ikuko Okazaki ◽  
Haruhiko Kamata ◽  
Masahiko Sasaki ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Active Site ◽  
Biological Activities ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene

Comparative biological activities of highly potent active-site analogs of .alpha.-melanotropin

1982 ◽  
Vol 25 (9) ◽  
pp. 1022-1027 ◽  
Author(s):  
Tomi K. Sawyer ◽  
Victor J. Hruby ◽  
Brian C. Wilkes ◽  
Matthew T. Draelos ◽  
Mac E. Hadley ◽  
...  
Keyword(s):  
Active Site ◽  
Biological Activities

scholarly journals Synthesis and Biological Activity Evaluation of Coumarin-3-Carboxamide Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1653
Author(s):  
Weerachai Phutdhawong ◽  
Apiwat Chuenchid ◽  
Thongchai Taechowisan ◽  
Jitnapa Sirirak ◽  
Waya S. Phutdhawong
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Active Site ◽  
Biological Activities ◽  
Docking Study ◽  
Cancer Cell Lines ◽  
Positive Control ◽  
Gram Negative Bacteria ◽  
Molecular Docking Study ◽  
Benzamide Derivatives

A series of novel coumarin-3-carboxamide derivatives were designed and synthesized to evaluate their biological activities. The compounds showed little to no activity against gram-positive and gram-negative bacteria but specifically showed potential to inhibit the growth of cancer cells. In particular, among the tested compounds, 4-fluoro and 2,5-difluoro benzamide derivatives (14b and 14e, respectively) were found to be the most potent derivatives against HepG2 cancer cell lines (IC50 = 2.62–4.85 μM) and HeLa cancer cell lines (IC50 = 0.39–0.75 μM). The activities of these two compounds were comparable to that of the positive control doxorubicin; especially, 4-flurobenzamide derivative (14b) exhibited low cytotoxic activity against LLC-MK2 normal cell lines, with IC50 more than 100 μM. The molecular docking study of the synthesized compounds revealed the binding to the active site of the CK2 enzyme, indicating that the presence of the benzamide functionality is an important feature for anticancer activity.

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