STUDY OF THE INTERACTION BETWEEN OXICAM DERIVATIVES AND COX1 USING FINGERPRINT DESCRIPTORS AND MOLECULAR DOCKING

2021 ◽  
Vol 21 (2) ◽  
pp. 529-538
Author(s):  
MANUEL AMZOIU ◽  
FLORENTINA CRISTOVICI ◽  
DENISA AMZOIU ◽  
FLORICA POPESCU ◽  
ALEXANDRA NITULESCU ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular State ◽  
Electron Acceptors ◽  
Hydroxyl Group ◽  
Docking Method ◽  
Thiazine Ring ◽  
Inhibitory Activities ◽  
Cox 1 ◽  
Nucleophilic Center ◽  
Oxygen Atoms

Oxicam derivatives play an important role in the treatment of pain and inflammation. The mechanism of action of these compounds consists in the inhibition of cyclooxygenase (COX) and the blockade of isoform 1 of this enzyme (COX-1) is considered to generate adverse effects. The aim of this paper is to establish which of the atoms in the oxicams molecules are responsible for their inhibitory activities, using electronegativity as fingerprint descriptor. Using this descriptor and molecular docking programs, the atoms in the molecule that have a greater contribution to COX-1 inhibition have been identified. In the case of the studied molecules, the oxygen atoms and the nitrogen atoms are highlighted. The oxygen atoms participate in the interaction as electron acceptors through U-MO molecular levels (74.1%) and the nitrogen atoms participate in the interaction both as a nucleophilic center through the molecular state of HOMO (13.7%) and as an electrophilic center through the molecular state of LUMO (13.2%). In the case of three out of four of the studied compounds, the 4-hydroxyl group of the thiazine ring participates in the interaction with COX-1. The results are also supported by the 2D and 3Ddiagrams of the applied docking method.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibitory activities and molecular docking studies of substituted 2-mercapto-4(3H)-quinazolinones

2016 ◽  
Vol 121 ◽  
pp. 410-421 ◽  
Author(s):  
Alaa A.-M. Abdel-Aziz ◽  
Laila A. Abou-Zeid ◽  
Kamal Eldin H. ElTahir ◽  
Rezk R. Ayyad ◽  
Magda A.-A. El-Sayed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Inhibitory Activities ◽  
Anti Inflammatory ◽  
Cox 1

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals Investigation of some benzoquinazoline and quinazoline derivatives as novel inhibitors of HCV-NS3/4A protease: biological, molecular docking and QSAR studies

RSC Advances ◽  
2020 ◽  
Vol 10 (59) ◽  
pp. 35820-35830 ◽  
Author(s):  
Hatem A. Abuelizz ◽  
Mohamed Marzouk ◽  
Ahmed H. Bakheit ◽  
Rashad Al-Salahi
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
Therapeutic Targets ◽  
Qsar Studies ◽  
Quinazoline Derivatives ◽  
Inhibitory Activities

HCV NS3/A4 protease inhibitors are one of the best therapeutic targets for the identification of novel candidate drugs. A series of benzo[g]quinazolines and their quinazoline analogues were evaluated for their HCV-NS3/4A inhibitory activities.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives

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 ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Anti Inflammatory ◽  
Cox 1

scholarly journals Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Belinda D. P. M. Ratu ◽  
Widdhi Bodhi ◽  
Fona Budiarso ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Docking Method ◽  
Pubmed Database ◽  
Almost All ◽  
The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak  melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

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