scholarly journals Pemodelan Molekuler Peptida Bioaktif Laut sebagai Antikoagulan Alami terhadap Enzim Sitokrom P450 (CYP) 2C9

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Cytochrome P450 ◽  
Bioactive Peptides ◽  
Blue Mussel ◽  
Enzyme Inhibitor ◽  
Therapeutic Potential ◽  
Peptide Sequencing ◽  
Bioactive Peptide ◽  
Bleeding Complications ◽  
Peptide Docking ◽  
Yellowfin Sole

Anticoagulants are very important for the treatment and prevention of thrombotic disorders. The use of conventional anticoagulants like heparin and warfarin can cause bleeding complications. To find safer anticoagulant therapy agents, the development of isolation of new anticoagulant compounds has shifted towards natural sources. Bioactive peptides can be considered a better alternative because of their therapeutic potential in the treatment of various diseases. Several peptide molecules have been shown to inhibit the cytochrome P450 (CYP) 2C9 enzyme as a natural anticoagulant, such as bioactive peptides produced by yellowfin sole (Limanda aspera) and bioactive peptides in blue mussel (Mytilus edulis). This study aims to identify and evaluate the interactions that occur between peptide molecules with the cytochrome P450 (CYP) 2C9 enzyme using protein-peptide docking methods. Bioactive peptide sequencing was modeled using the PEP-FOLD software. The best conformation was chosen for an interaction study against the macromolecule of cytochrome P450 (CYP) 2C9 enzyme using PatchDock software. Further observations were made of interactions formed using BIOVIA Discovery Studio 2020 software. Based on the results of protein-peptide docking, the yellowfin sole peptide molecule has a good affinity against the macromolecule of cytochrome P450 (CYP) 2C9 enzyme, with an ACE score of −2527.01 kJ / mol. Therefore, the bioactive peptide is predicted to be used as a candidate for the cytochrome P450 (CYP) 2C9 enzyme inhibitor.

scholarly journals Identifikasi Peptida Bioaktif dari Protein Kedelai sebagai Inhibitor Enzim α-glukosidase untuk Kandidat Antidiabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 101-109
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Molecular Interactions ◽  
Metabolic Disorders ◽  
Enzyme Inhibitor ◽  
Therapeutic Potential ◽  
Binding Free Energy ◽  
Peptide Sequencing ◽  
Bioactive Peptide ◽  
Suitable Candidate ◽  
Discovery Studio ◽  
Peptide Docking

Diabetes mellitus is one of the endocrine metabolic disorders that has caused morbidity and mortality worldwide. Α-glucosidase inhibitor which plays an important role in carbohydrate metabolism is needed to avoid postprandial hyperglycemia. A bioactive peptide derived from soy protein was chosen as an alternative treatment for diabetes because of its therapeutic potential. Several bioactive peptides have been shown to inhibit the α-glucosidase enzyme, such as the bioactive peptide LLPLPVLK, SWLRL, and WLRL. This study aims to identify and evaluate molecular interactions that occur between bioactive peptide molecules and α-glucosidase enzyme macromolecules using protein-peptide docking methods through in silico. Bioactive peptide sequencing was first modeled using the PEP-FOLD software. The best conformation was chosen for an interaction study of the α-glucosidase enzyme macromolecule using HPEPDock software. Further exploration was carried out on the molecular interactions formed using BIOVIA Discovery Studio 2020 software. Based on the results of molecular docking, the WLRL bioactive peptide has the best affinity against the α-glucosidase enzyme, with a binding free energy value of −748.12 kJ/mol. Therefore, the bioactive peptide is predicted to be a suitable candidate for the α-glucosidase enzyme inhibitor.

scholarly journals Mengidentifikasi Peptida Bioaktif Angiotensin Converting Enzyme-inhibitor (ACEi) dari Kasein β Susu Kambing dengan Polimorfismenya Melalui Teknik In Silico

2019 ◽  
Vol 7 (4) ◽  
Author(s):  
Hermawan Setyo Widodo ◽  
Tridjoko Wisnu Murti ◽  
Ali Agus ◽  
Widodo Widodo
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Digestive Enzymes ◽  
Bioactive Peptides ◽  
Enzyme Inhibitor ◽  
Goat Milk ◽  
Bioactive Peptide ◽  
Converting Enzyme ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

Susu kambing memiliki komponen protein salah satunya protein β dan secara umum terjadi polimorfisme pada level protein. Perubahan urutan asam amino akibat polimorfisme memungkinkan adanya potensi dihasilkannya peptida bioaktif penghambat enzim pengubah angiotensin (ACEi). Penelitian ini bertujuan untuk menyaring peptida bioaktif yang berpotensi sebagai ACEi dari kasein β kambing beserta polimorfismenya. Penelitian ini dilakukan dengan teknik in silico terhadap sekuen kasein β kambing serta struktur tiga dimensi human testicular ACE. Langkah yang dilakukan dalam penelitian ini meliputi simulasi pemotongan peptida dengan enzim pencernaan (pepsin, tripsin dan kimotripsin), peninjauan karakteristik peptida lalu simulasi docking ligan-reseptor. Tampilan parameter Lipinski’s Rule of Five (Ro5), bioaktivitas dan energi afinitas dipertimbangkan untuk memilih peptida bioaktif. Hasil yang didapat menunjukkan bahwa ditemukan peptida bioaktif yakni INK (Ile-Asp-Lys) yang memiliki kemampuan hampir setara dengan lisinopril (afinitas energi -8,2kkal/mol vs. -8,3kkal/mol). Peptida INK dapat ditemukan dari hasil hidrolisis dari alel A, C, D dan E, sehingga polimorfisme tidak menyebabkan perbedaan produksi peptida bioaktif. Kesimpulan yang dapat diambil yakni kasein β susu kambing jika dicerna dengan enzim pencernaan dapat menghasilkan peptida bioaktif ACEi yakni INK.Identification of Angiotensin Converting Enzyme-inhibitor (ACEi) Bioactive Peptide from Goat Milk β-Casein with It's Polymorphism by In Silico TechniqueAbstractPolymorphism eventually may be occurred at the protein level. Changes in the amino acid sequence due to polymorphism may exhibit a potential action to generate of the angiotensin-converting enzyme inhibitors (ACEi) bioactive peptide. This study is aimed to assess bioactive peptides that have a great potent value as ACEi from goat β casein along with its polymorphism. The research was done by in silico technique on goat β-casein sequence and three-dimensional structure human testicular ACE. Peptide-cutting simulations with digestive enzymes (pepsin, trypsin and chymotrypsin), peptide properties review, then ligand-receptor docking simulations was applied in this research. Appearance of Lipinski's Rule of Five (Ro5), bioactivity and affinity energy were considered for selecting bioactive peptides. The results show that bioactive peptide found as INK (Ile-Asp-Lys) which had similar ability as lisinopril (energy affinity –8.2kcal/mol vs. –8.3kcal/mol). The INK peptides could be found from the hydrolysis resulted in alleles A, C, D and E, therefore polymorphism did not affect the differences of production of bioactive peptides. A conclusion, processed goat milk β casein with digestive enzymes could produce ACEi of INK as bioactive peptide.

Abstract 1359: Evaluation of the therapeutic potential of AIMZ-938 as a new cytochrome p450 1A1-selective prodrug for the treatment of breast cancers

2021 ◽  
Author(s):  
Atziri Corin Chavez Alvarez ◽  
Chahrazed Bouzriba ◽  
Mathieu Gagné-Boulet ◽  
Sylvie Pilote ◽  
René C.-Gaudreault ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Therapeutic Potential ◽  
Breast Cancers ◽  
Cytochrome P450 1A1

scholarly journals In Silico Bioactive Peptide Prediction from The Enzymatic Hydrolysates of Edible Seaweed Rubisco Large Chain

2021 ◽  
Vol 21 (12) ◽  
pp. 615-625
Author(s):  
Ayse Kose
Keyword(s):  
In Silico ◽  
Bioactive Peptides ◽  
Antioxidant Properties ◽  
In Silico Analysis ◽  
Bioactive Peptide ◽  
Bioactive Substances ◽  
Edible Seaweed ◽  
Ic50 Values ◽  
Peptide Prediction ◽  
Ancient Food

Seaweeds are one of the ancient food supplements on Earth. Especially Asian countries use seaweeds as the fundamental ingredient in their cuisine. Seaweeds are photosynthetic organisms living in aquatic ecosystems and in the coastal territories. Seaweeds out of farm areas are frequently observed as coastal wastes. However, seaweeds are outstanding sources for bioactive substances and investigation bioactive properties of seaweed RuBisCO has never been done. RuBisCO is the most abundant protein on Earth but a vast amount of RuBisCO goes through waste. In this study, bioactive peptide prediction of frequently consumed seaweed RuBisCO proteins were analyzed in silico to identify possible bioactive peptides as substitute or support for grain, meat, and dairy based bioactive peptides. A huge portion of peptides were di-, tri- peptides with IC50 values less than 300 µM according to the comparison of BIOPEP database. Including gastric digestion, more than half of the peptides showed DDP-IV and ACE inhibitory activity followed by antioxidant properties. Also, novel antiinflammatory and anti-cancer peptides were found through in silico analysis.

Therapeutic Potential of Choline Magnesium Trisalicylate as an Alternative to Aspirin for Patients with Bleeding Tendencies

1987 ◽  
Vol 32 (6) ◽  
pp. 167-168 ◽  
Author(s):  
B.J.Z. Danesh ◽  
A.R. Saniabadi ◽  
R.I. Russell ◽  
G.D.O. Lowe
Keyword(s):  
Salicylic Acid ◽  
Platelet Aggregation ◽  
Whole Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Random Order ◽  
Bleeding Complications ◽  
Double Blind ◽  
Inhibition Of Platelet Aggregation ◽  
Spontaneous Aggregation

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p<0.005), AA (p<0.01) and spontaneous aggregation (p<0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and hormonal function in heart failure

2002 ◽  
Vol 103 (s2002) ◽  
pp. 254S-257S ◽  
Author(s):  
Atsuyuki WADA ◽  
Masato OHNISHI ◽  
Takayoshi TSUTAMOTO ◽  
Masanori FUJII ◽  
Takehiro MATSUMOTO ◽  
...  
Keyword(s):  
Heart Failure ◽  
Enzyme Inhibitor ◽  
Therapeutic Potential ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Converting Enzyme ◽  
Hormonal Function ◽  
Chronic Effects ◽  
Significant Difference ◽  
Body Fluid Balance

Endothelin (ET)-converting enzyme (ECE) is a rate-limiting step in ET-1 generation, and its expression and activity are increased significantly with the development of congestive heart failure (CHF). The selective enzymic inhibition of ET-1 formation thus seems to be a very important target in the prevention of CHF. We evaluated the chronic effects of a specific ECE inhibitor, FR901533 (0.3mg·kg-1·h-1, n = 5) on cardiac, hormonal, and body fluid balance in dogs with CHF induced by rapid right ventricular pacing (270beats/min, 22 days). Vehicle dogs were given placebo (n = 5). Despite no significant difference in blood pressure, FR901533 decreased pulmonary capillary wedge pressure and increased cardiac output compared with the vehicle. FR901533 prevented the reduction of urine flow rate and urinary sodium excretion in association with an increase in the glomerular filtration rate and renal plasma flow compared with the vehicle. FR901533 also suppressed significantly the elevation of plasma atrial natriuretic peptide and aldosterone levels which is an established prognostic factor in CHF. These results indicate that the role of ECE in CHF is important and that chronic ECE inhibition could possess therapeutic potential in the treatment of CHF not only on haemodynamics but also in the prevention of fluid retention.

COMPARISON OF THE EFFECT OF ASPIRIN (ASA) AND CHOLINE MAGNESIUM TRISALICYLATE (CMT) ON PLATELET AGGREGATION IN WHOLE BLOOD EX-VIVO

1987 ◽  
Author(s):  
B J Z Danesh ◽  
A R Saniabadi ◽  
R I Russell ◽  
G D O Lowe ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Random Order ◽  
Blood Platelet ◽  
Bleeding Complications ◽  
Double Blind ◽  
Inhibition Of Platelet Aggregation ◽  
Spontaneous Aggregation

Suppression of platelet aggregation by ASA limits the therapeutic use of this drug as an analgesic in patients with bleeding tendencies. CMT is a non-acetylated salicylate derivative with analgesic and anti-inflammatory effect similar to that of ASA. We compared platelet aggregation in human whole blood ex-vivo, three hours after ingestion of ASA and. CMT. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen (lμg/ml) arachidonic acid (AA, 0.5 mM) as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received a single oral dose of ASA and CMT containing 500 mg equivalent salicylate, on two separate occasions, 10 days apart. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen, AA and spontaneous aggregation, whereas such effects were not observed after CMT ingestion.We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

scholarly journals Accelerated Metabolism of Voriconazole and Its Partial Reversal by Cimetidine

2009 ◽  
Vol 53 (4) ◽  
pp. 1712-1714 ◽  
Author(s):  
Brad Moriyama ◽  
Jason Elinoff ◽  
Robert L. Danner ◽  
Juan Gea-Banacloche ◽  
Gennethel Pennick ◽  
...  
Keyword(s):  
Body Weight ◽  
Cytochrome P450 ◽  
Enzyme Inhibitor ◽  
Invasive Pulmonary Aspergillosis ◽  
Cytochrome P450 Enzyme ◽  
Pulmonary Aspergillosis ◽  
P450 Enzyme ◽  
Partial Reversal

ABSTRACT We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme inhibitor.

The Antihypertensive, Antimicrobial and Anticancer Peptides from Arthrospira with Therapeutic Potential: A Mini Review

2020 ◽  
Vol 20 (8) ◽  
pp. 593-606
Author(s):  
Grecia E. Barriga Montalvo ◽  
Luciana Porto de Souza Vandenberghe ◽  
Vanete Thomaz Soccol ◽  
Júlio Cesar de Carvalho ◽  
Carlos Ricardo Soccol
Keyword(s):  
Bioactive Peptides ◽  
Therapeutic Potential ◽  
Inhibition Mechanism ◽  
Therapeutic Effects ◽  
High Concentration ◽  
Tumour Control ◽  
Anticancer Peptides ◽  
Inhibition Of Angiogenesis ◽  
History Of ◽  
Purification Methods

: The interest in biological peptides from Arthrospira sp. (syn Spirulina) is increasing due to its Generally Recognised as Safe “GRAS” status, the high concentration of proteins and the history of its use as a supplement and nutraceutical agent. Arthrospira peptides can be generated by the controlled hydrolysis of proteins, using proteases, followed by fractionation. The peptides obtained have a range of therapeutic effects. Amongst these bioactive peptides, three classes are of major importance: the antihypertensive (AHP), antimicrobial (AMP) and anticancer (ACP) peptides. AHPs have the ability to work as inhibitors of angiotensin-converting enzyme (ACE), and help to control several diseases such as hypertension, obesity, and cardiovascular issues, AMPs play a crucial role in the immune response, inhibiting the development of pathogens such as bacteria, fungi, viruses and others, while ACPs can aid in tumour control by the induction of apoptosis or necrosis, or the inhibition of angiogenesis. Thus, bioactive peptides are of great significance to the pharmaceutical industry. However, they can show secondary effects. This paper reviews the inhibition mechanism of antimicrobial, hypertensive and anticancer peptides from Arthrospira sp., and the possible structures of the peptides according to the type of activity and its intensity. In addition, this paper describes the purification methods of absorption mechanisms, and reviews databases for designing peptides.

Acetylcholinesterase Enzyme Inhibitor Molecules with Therapeutic Potential for Alzheimer's Disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Bhuvaneswari Siwaraman ◽  
Vijaykumar R. ◽  
Bala Aakash Velmurugan ◽  
Ramalakshmi Natarajan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Inhibitor ◽  
Therapeutic Potential ◽  
Psychological Symptoms ◽  
Heteroaromatic Compounds ◽  
The Central Nervous System ◽  
The Many ◽  
Acetylcholinesterase Enzyme ◽  
Ellman’S Method

: Acetylcholinesterase (AchE), hydrolase enzyme, regulates the hydrolysis of acetylcholine neurotransmitter in the neurons. AchE is found majorly in the central nervous system at the site of cholinergic neurotransmission. It is involved in the pathophysiology of Alzheimer’s disease-causing dementia, cognitive impairment, behavioral and psychological symptoms. Recent findings involved the inhibition of AchE that could aid in the treatment of Alzheimer's. Many drugs of different classes being analyzed in the clinical trials and examined for their potency. Drugs that are used in the treatment of Alzheimer’s disease are donepezil, galantamine, tacrine, rivastigmine shows major adverse effects. To overcome this, researchers work on novel drugs to elicit inhibition. This review comprises the many hybrids and non-hybrid forms of heteroaromatic and non-heteroaromatic compounds that were designed and evaluated for AchE inhibition by Ellman’s method of assay. These novel compounds may assist the future perspectives in the discovery of novel moieties against Alzheimer’s disease by the inhibition of AchE.

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