scholarly journals STRUCTURE-BASED DOCKING STUDIES TOWARD EXPLORING THE POTENTIAL ANTICANCER ACTIVITY OF MORIN AGAINST NON-MELANOMA SKIN CANCER THERAPEUTIC DRUG TARGETS

2018 ◽  
Vol 11 (4) ◽  
pp. 61
Author(s):  
Anjugam C ◽  
Sridevi M ◽  
Gnanendra Ts
Keyword(s):  
Binding Energy ◽  
Anticancer Activity ◽  
Drug Targets ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Peroxisome Proliferator ◽  
Non Melanoma Skin Cancer ◽  
Cox 2 ◽  
Peroxisome Proliferator Activated Receptors ◽  
In Silico Molecular Docking

 Objective: The purpose of this study is to explore the anticancer activity of morin compound against human cyclooxygenase-2 (COX-2) and peroxisome-proliferator-activated receptors (PPARs) isotypes (PPARα and PPARγ) through in silico molecular docking studies.Methods: The 3D structures of human COX-2 complexed with ibuprofen (PDB ID: 4PH9), PPARα complexed with a synthetic agonist (2S)-2-(4- methoxy-3-{[(pyren-1-yl carbonyl) amino] methyl} benzyl) butanoic acid (PDB ID: 3VI8) and PPARγ complexed indomethacin (PDB ID: 3ADX) were retrieved from protein databank. The cocrystallized sites were considered as binding sites, and the docking with morin compound was performed along with their respective cocrystals for each target and compared their interactions and binding affinities.Results: It is observed that the morin compound exhibited better binding energy of -32.9528 kJ/mol against PPARα followed by COX-2 (binding energy: −18.4311 kJ/mol) and PPARγ (binding energy: −17.4228 kJ/mol) when compared to their cocrystallized ligands.Conclusion: The present study suggests that morin compound might serve as potential alternatives in the prevention of skin cancers by showing better activity against PPARα.

scholarly journals Molecular docking studies of potential anticancer agents from Thunbergia Fragrans against Colorectal cancer mutant genes through In silico study

2021 ◽  
Vol 12 (4) ◽  
pp. 792-795
Author(s):  
Charankumar Chandrasekaran ◽  
Ramar K
Keyword(s):  
Colorectal Cancer ◽  
Binding Energy ◽  
Palmitic Acid ◽  
Anticancer Activity ◽  
Chemical Constituents ◽  
Docking Studies ◽  
Flowering Plant ◽  
Beta Catenin ◽  
Effective Manner ◽  
Mutant Genes

Colorectal cancer (CRC) is one of the deadly diseases which incidence rate will increase every year due to people lifestyle and food habit etc., Moreover, people’s required a new therapeutic molecule to resolve this problem. Therefore plant-based chemical constituents are the best option due to the low side effects, easy availability and cost-effective manner. The flowering plant of Thunbergia fragrans Roxb belongs to the Acanthaceae family has a vast range of medicinal properties, anticancer activity is one among them. Thunbergia fragrans has reported to had chemical constituents of Palmitic acid, Cis-9-Hexadecenal and Campesterol which possess anticancer activity. For the beginning of TF chemical constituents were studied against the Colorectal cancer (CRC) mutant genes such as NRAS (PDB ID: 6ZIZ), Beta-Catenin (PDB ID: 6M93) – Oncogenes; APC (PDB ID: 3NMX), Smad2 (PDB ID: 1KHU) – Tumor Suppressor genes through insilico docking studies. AutoDock 4.2 tool was used to predict the interaction between ligand and receptor, Binding energy and Bond specification in a 3D space. Finally, the results revealed TF chemical constituents showed excellent binding energy against CRC mutant genes such as Palmitic acid against Beta-Catenin (-4.75) and APC (-4.01), Cis-9-Hexadecenal against NRAS (-1.92), Beta-Catenin (-3.96) and APC (-4.41), Campesterol against Beta-Catenin (-8.55) and APC (-8.85) respectively. 

scholarly journals PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

2021 ◽  
Vol 22 (16) ◽  
pp. 8974
Author(s):  
Chen Sun ◽  
Shuyu Mao ◽  
Siyu Chen ◽  
Wenxiang Zhang ◽  
Chang Liu
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Unique Role ◽  
Molecular Events ◽  
Peroxisome Proliferator Activated Receptors ◽  
Whole Body Metabolism ◽  
Metabolic Syndromes

It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to “safely” store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.

scholarly journals DOCKING STUDY OF ALLICIN WITH SULFONYLUREA RECEPTOR 1, COMPLEX 1 AND PPARγ RECEPTOR ON INSULIN RESISTANCE

2018 ◽  
Vol 10 (10) ◽  
pp. 130 ◽  
Author(s):  
Muhammad Andre Reynaldi ◽  
Hafrizal Riza ◽  
Sri Luliana
Keyword(s):  
Insulin Resistance ◽  
Binding Energy ◽  
Physicochemical Properties ◽  
Docking Study ◽  
Log P ◽  
Peroxisome Proliferator ◽  
Sulfonylurea Receptor ◽  
Docking Method ◽  
Sulfonylurea Receptor 1 ◽  
Peroxisome Proliferator Activated Receptors

Objective: Allicin is a potential type 2 antidiabetic. Sulfonylurea receptor 1 (SUR1), nikotinamida adina dinukleotida dehydrogenase (Complex 1) and peroxisome proliferator-activated receptors gamma (PPARγ) are known as important receptors responsible in insulin resistance This study aimed to determine the physicochemical properties, and the affinity of allicin on SUR1, Complex 1 and PPARγ receptors based on the binding energy and the type of interaction.Methods: The physicochemical properties of allicin were analyzed using ChemOffice, and the binding energy and type of interaction were analyzed using the docking method with Autodock Vina.Results: The results from the analysis showed allicin has log p (logarithmic partition) 1.35, massa relativity (mr) 162.26 g/mol, and the binding energy of allicin on SUR1, Complex 1 and PPARγ are respectively-4.0;-3.0; and-4.1 kcal/mol. The type of interaction between allicin and receptors is van der waals.Conclusion: Allicin has good permeability and has the potential to bind to SUR1, Complex 1 and PPARγ receptors contributing to the activity of allicin as antidiabetic.

scholarly journals Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3849
Author(s):  
Jasmine Siew Min Chia ◽  
Ahmad Akira Omar Farouk ◽  
Tengku Azam Shah Tengku Mohamad ◽  
Mohd Roslan Sulaiman ◽  
Hanis Zakaria ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Docking Studies ◽  
Peroxisome Proliferator ◽  
Chronic Pain Condition ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pain Symptoms ◽  
In Silico Models

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone’s antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB1 receptor), SR144528 (CB2 receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB1, PPARα and PPARγ in zerumbone’s action against mechanical allodynia, whereas only CB1 and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.

scholarly journals Hasil In Silico Senyawa Z12501572, Z00321025, SCB5631028 dan SCB13970547 dibandingkan Turunan Zerumbon terhadap Human Liver Glycogen Phosphorylase (1l5Q) sebagai Antidiabetes

2016 ◽  
Vol 2 (2) ◽  
pp. 120-124
Author(s):  
Fitri Kusvila Aziz ◽  
Cantika Nukitasari ◽  
Fauziyah Ardli Oktavianingrum ◽  
Lita Windy Aryati ◽  
Broto Santoso
Keyword(s):  
Binding Energy ◽  
Human Liver ◽  
Drug Targets ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Docking Studies ◽  
Ligand Interaction ◽  
Drug Compounds ◽  
Protein Ligand Interaction ◽  
And Control

Abstrak Human Liver Glycogen Phosphorylase (HLGP), suatu katalis glikogen yang mengontrol pelepasan glukosa-1-fosfat glikogen dari hati. Enzim ini mempunyai peran sentral dalam luaran glukosa hati sehingga menjadi target obat antidiabetik. Kajian docking dilakukan pada komputer dengan prosesor Intel Pentium, RAM 1 GB dan Windows 7. Ligan yang digunakan adalah senyawa obat (Z12501572, Z00321025, SCB5631028 dan SCB13970547), dataset pembanding aktif glycogen phosphorylase outer dimer site (PYGL-out) dan decoysdari www.dekois.com dan turunan zerumbon. Protein dipisahkan dari ligan nativ dan semua ligan beserta protein dikonversi menggunakan PyRx. Visualisasi interaksi ligan-protein dihasilkan dengan program Protein-Ligand Interaction Profiler (PLIP) dan PyMOL. Senyawa ZER11 memiliki binding energy terbaik, yaitu -7.11 kkal/mol (untuk metode LGA dan GA) dan -4.08 kkal/mol untuk metode SA. Nilai binding energy tersebut lebih rendah dari pada nilai untuk ligan native dan satu dari keempat senyawa obat, terlebih jika dibandingkan dengan bindingaffinity dari dataset dan decoys. Interaksi ligan-protein pada ketiga metode tersebut ditemukan sangat bervariasi. Hal berbeda terjadi untuk metode Vina, bindingenergy ZER11 (-9.9 kkal/mol) lebih baik dibandingkan dengan ligan native dan keempat senyawa obat. Senyawa ZER11 memiliki residu interaksi yang sama dengan ligan native pada TRP67 dan LYS191 untuk metode Vina. Kata kunci: PDBID-1L5Q, AutoDock, docking molekuler, vina, antidiabetes   Abstract Human Liver Glycogen Phosphorylase (HLGP) can catalyze glycogen and control the release of glucose-1-phosphate of glycogen from the liver. This enzyme has a central role in output rule of liver glucose as it can be used as an antidiabetic drug targets. Docking studies were carried out on PC with Intel Pentium, 1 GB RAM, in environment of Windows 7. Ligands used are drug compounds (Z12501572, Z00321025, SCB5631028 and SCB13970547), the active dataset comparator wasglycogenphosphorylase outer dimer site (PYGL-out) and decoys from www.dekois.com andzerumbonederivates. Protein was separated from its native ligand and all ligands including the protein were converted to pdbqt using PyRx. The interaction of protein-ligand was visualized using software of PLIP and PyMOL. Compound of ZER11 had the best binding energy were -7.11 kcal/mol (LGA and GA) and -4.08 kcal/mol (SA). The binding energy value was lower than the ligand native and one of the four drug compounds, especially compared with the binding affinity of dataset and decoys. Vice versa, for Vina method, the value of ligand binding protein for ZER11 (-9.9 kcal/mol) was better than the ligand native and all of the fourth drugcompounds. Vina result showed that ZER11 had the same residual interaction as the ligand native, which are TRP67 and LYS191. Keyword: PDBID-1L5Q, AutoDock, molecular docking, vina, antidiabetic DOI: http://dx.doi.org/10.15408/jkv.v0i0.4170

In silico molecular docking studies and ADME/T analysis of Some Flavonoids against the target of Mpro inCOVID-19

2020 ◽  
Vol 10 (2) ◽  
pp. 33-46
Author(s):  
Kaviarasu J ◽  
Suresh Kumar CA ◽  
Naimuddeen N
Keyword(s):  
Binding Energy ◽  
Development Process ◽  
Docking Studies ◽  
Lung Damage ◽  
Effective Vaccine ◽  
Kcal Mole ◽  
Respiratory Complications ◽  
Global Pandemic ◽  
In Silico Molecular Docking ◽  
Native Ligand

COVID-19 may be a devastating global pandemic round the world. While the bulk of infected cases appear mild, in some cases individuals present respiratory complications with possible serious lung damage. This virus can infect both animals and other people and its control are very difficult because there's no effective vaccine or drugs available in markets for the treatments for COVID-19 so far. During this study we docked the flavonoids against the target protein Mpro(6lu7) shows the binding energy between -8.68 kcal/mole to -6. 68 kcal/mol compare to native ligand (PRD_002214). The compounds Catechins, Luteoforol, Sappanchal-cone, Baicalein, Vitexin, Chrysosplenol, 5,6,7-Trimeth-oxyflavone showed almost equal binding energy towards the native ligand except Genistein. Our analyses revealed that the highest nine hits might function potential anti- SARS-CoV-2 lead molecules for further innovation and drug development process to combat COVID-19 also nearly as good drug likeness properties studied supported the Lipinski’s rules of 5.

Synthesis and In-silico identification of new bioactive 1,3,4-oxadiazole tagged 2,3-dihydroimidazo[1,2-a]pyridine derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Bhagwat S. Jadhav ◽  
Vipul P. Purohit ◽  
Ramesh S. Yamgar ◽  
Rajesh S. Kenny ◽  
Suraj N. Mali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Pyridine Derivatives ◽  
Molecular Docking Studies ◽  
New Class ◽  
In Silico Molecular Docking

Background: Tuberculosis (TB) continues to be the most threatening cause of death in recent years. There is urgent need of search more potent, less toxic antitubercular agents. Methods: A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) was synthesized and screened invitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294. Results: Compound 4b displayed potent antitubercular activity at MIC 6.25 µg/mL. In-silico molecular docking studies were performed for evaluation of the binding patterns of compounds 4a-4e in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in- vitro antitubercular studies were in well agreement with the molecular docking studies. These newly synthesized compounds were found to have good ADMET profile. We also explored possible anticancer activity using in-silico methods. Conclusion: These results shows that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) are attracting new class of potent anti-TB targets as well as possible anticancer activity that worth additional opportunities for improvements.

scholarly journals STRUCTURE PREDICTION AND IN SILICO DESIGNING OF DRUGS AGAINST KALLIKREIN PROTEIN 12

2017 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
Manish Devgan
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Structure Prediction ◽  
Docking Studies ◽  
Receptor Protein ◽  
Loop Modeling ◽  
Autodock Vina ◽  
Potential Therapeutic Target ◽  
Plot Analysis ◽  
In Silico Molecular Docking

Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer.Methods: In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands.Results: The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted.Conclusion: Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient.

scholarly journals Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX-2/mPGES-1/PGE2Cascade

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Haiping Wang ◽  
Zhanjun Jia ◽  
Jing Sun ◽  
Liang Xu ◽  
Bing Zhao ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Kidney Injury ◽  
Histological Change ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Protective Effects ◽  
Plasma Urea ◽  
Lipid Product ◽  
Cox 2 ◽  
Peroxisome Proliferator Activated Receptors

Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2pretreatment group. In summary, the pretreatment with OA-NO2remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2cascade.

scholarly journals In-silico molecular docking analysis of some plant derived molecules for anti-inflammatory inhibitory activity

2021 ◽  
pp. 22-27
Author(s):  
L. Thamaraiselvi ◽  
T. Selvankumar ◽  
E.G. Wesely ◽  
N. Vinod Kumar
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Novel Drugs ◽  
In Silico Study ◽  
Low Toxicity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
In Silico Molecular Docking ◽  
Oxide Synthase

Herbs are essential resources for drug discovery. However, numerous challenges stand in front of the scientific community to discover novel drugs from herbs. To explore the validation behind the precious knowledge of traditional medicine, we focused on achieving virtual screening to detect the potential medicines from the herbs.  Five bioactive compounds from known anti-inflammatory medicinal plants were examined through molecular docking against  cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS), using AutoDock 4.2. The docking of selected ligands with COX-2 showed the binding energy varying from -6.15 Kcal/mol to ‑11.24 Kcal/mol. The docking energies of identified ligands with iNOS were generated ranges from -3.85kcal/mol to -6.99 kcal/mol.  Among the tested ligands, it was noted that 6 urs-12-en-24-oic acid showed the best binding energy than other compounds with the lowest binding energy and highest binding affinity with both anti-inflammatory target proteins COX-2 and iNOS. The in silico study validates the potential phytochemical compound of the medicinal herb that contribute to anti-inflammatory activity with low toxicity and minimal side effects.

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