scholarly journals Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid

2021 ◽  
Vol 9 ◽  
Author(s):  
Muhammad Alamzeb ◽  
William N. Setzer ◽  
Saqib Ali ◽  
Behramand Khan ◽  
Mamoon-Ur- Rashid ◽  
...  

A new bisbenzylisoquinoline named as chondrofolinol (1) and four reported compounds (2–5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of Leishmania tropica, respectively. The new compound significantly reduced the paw volume in carrageenan-induced paw edema and rectal temperature in yeast-induced pyrexia at 10 and 20 mg/ kg of body weight. Chondrofolinol caused almost 100% inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and UGPase. The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory, and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Haasini Nandyala ◽  
Ariel Pham ◽  
Anushka Wagle ◽  
Hansika Daggolu ◽  
Amrita Guha ◽  
...  

Abstract: Trigonella foenum-graecum has been shown to have anti-diabetic potential through a wide variety of in-vivo assays as well as by inhibiting enzymes such as alpha-glucosidase and alpha-amylase. Studies have indicated the therapeutic potential of different phytoconstituents found in Trigonella foenum-graceum including diosgenin trigonelline, 4-hydroxyisoleucine, leucine, and L-lysine. This study aims to find novel protein targets that these specific phytoconstituents from fenugreek can bind to, thereby helping to treat diabetes mellitus. Through multiple stages of molecular docking and analyzing the binding sites in comparison to previously reported inhibitors, a suitable and novel target protein for four of the compounds was found and the relevance to diabetes was discussed, setting up these compounds as novel inhibitors for the target proteins.


2019 ◽  
Vol 14 (1) ◽  
pp. 85-90
Author(s):  
Sagarika Biswas

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- &#945;). Recent drug designing studies are developing TNF-&#945; blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. </P><P> Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- &#945; and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. </P><P> Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-&#945; and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 &#181;M inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-&#945; in RA compared to control. </P><P> Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-&#945; mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.


2016 ◽  
Vol 24 (9) ◽  
pp. 2032-2042 ◽  
Author(s):  
Maged A. Abdel-Sayed ◽  
Said M. Bayomi ◽  
Magda A. El-Sherbeny ◽  
Naglaa I. Abdel-Aziz ◽  
Kamal Eldin H. ElTahir ◽  
...  

2018 ◽  
Vol 55 (12) ◽  
pp. 2901-2910 ◽  
Author(s):  
Dhansay Dewangan ◽  
Kartik T. Nakhate ◽  
Vinay Sagar Verma ◽  
Kushagra Nagori ◽  
Hemant Badwaik ◽  
...  

2020 ◽  
Vol 12 (1) ◽  
pp. 19
Author(s):  
Qi Wang ◽  
Tao Wei ◽  
Xiaoying Zhou

Dipeptidyl peptidase I (DPPI) and chymase, the granulo-proteases produced and released by mast cells, are important targets of anti-inflammatory drug research and development. Cortex Dictamni is a definite nature drug with anti-inflammatory activity, but the mechanism is unclear and effects of Cortex Dictamni on DPPI and chymase are unknown. This study focuses on effects of Cortex Dictamni aqueous extract (CDAE) on DPPI and chymase activities using cell model, bio-molecular interactions and the Molecular docking study by Discovery Studio (DS) analysis. The results showed that CDAE could significantly inhibit DPPI and chymase activities in vitro and in living rat spleen lymphocytes. Molecular docking simulation demonstrated that Troxerutin, the one of the active compounds of Cortex Dictamni, formed a hydrogen bond with amino acid ILE429 and a strong hydrophobic interaction with TYR64 CYS234 PRO279 ALA382 of DPPI. These interactions allow Troxerutin to form a stable complex with the DPPI, implicating that Troxerutin might be a potential natural inhibitor of DPPI. Dictamnoside M, another active compound of Cortex Dictamni formed hydrogen bonds and hydrophobic interactions within the binding pocket of chymase domain and form a stable complex with the chymase. Dictamnoside M maybe a potential natural inhibitor of chymase. This study suggested a new nature inhibitor Cortex Dictamni and its active components with the anti-inflammatory effects.


Author(s):  
S. A. Khedkar ◽  
J. S. Patil ◽  
P. M. Sabale

Drug design and development is an interactive process includes process like molecular docking which involves virtual analysis of the derivatives against the protein targets. COXS are the groups of enzymes which plays vital role in the human process. COX II is important enzyme involved in the inflammation and can act as potential target for development of the potent anti-inflammatory agents. Pyrimidine is one of the most utilized heterocyclic scaffolds for the development of therapeutic agents due to its role in the nucleic acid and proteins in the human body. The present communication deals with docking analysis of virtually designed 58 condensed pyrimidine derivatives as potential anti-inflammatory agents. The derivatives were designed and virtually screened via molecular docking against the COX-II crystal structure to identically the potential leads.


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