scholarly journals In-silico Study of Seaweed Secondary Metabolites as AXL Kinase Inhibitors

2021 ◽  
Author(s):  
Lavanya Nagamalla ◽  
J.V. Shanmukha Kumar ◽  
Chintakindi Sanjay ◽  
Ali M Alsamhan ◽  
Mohammed Rafi Shaik
Keyword(s):  
Secondary Metabolites ◽  
In Silico ◽  
Kinase Inhibitors ◽  
In Silico Study

scholarly journals Studi In Silico Metabolit Sekunder Kapang Monascus sp. sebagai Kandidat Obat Antikolesterol dan Antikanker

2019 ◽  
Vol 15 (1) ◽  
pp. 104
Author(s):  
Marlia Singgih ◽  
Benny Permana ◽  
Selvira Anandia Intan Maulidya ◽  
Anna Yuliana
Keyword(s):  
Secondary Metabolites ◽  
Anticancer Drugs ◽  
In Silico ◽  
Natural Food ◽  
Toxicity Prediction ◽  
Bioactive Constituents ◽  
Food Preservative ◽  
In Silico Study ◽  
Dimerumic Acid ◽  
Coa Reductase

<p>Kapang <em>Monascus </em>sp<em>. </em>secara tradisional telah digunakan dalam fermentasi beras merah (angkak) yang bermanfaat sebagai pewarna makanan, pengawet makanan maupun obat-obatan. Saat ini, beras angkak telah menjadi suplemen makanan yang terkenal karena banyaknya senyawa bioaktif yang terkandung seperti monakolin, pigmen, asam dimerumat dan lain-lain. Tujuan penelitian ini adalah untuk menemukan metabolit sekunder kapang <em>Monascus </em>sp<em>.</em> yang meliputi senyawa monakolin dengan efek antikolesterol, pigmen dengan efek antikanker pada kanker payudara serta memprediksi toksisitas senyawa melalui studi <em>in silico.</em> Senyawa uji terdiri dari 14 senyawa monakolin dan 33 pigmen <em>Monascus </em>sp. Protein HMG KoA (3-hidroksi-3-metilglutaril koenzim A) reduktase digunakan sebagai reseptor antikolesterol sementara estrogen alfa, estrogen beta, dan aromatase digunakan sebagai reseptor antikanker. Perangkat lunak AutoDock digunakan untuk menganalisis kompleks struktural reseptor dengan senyawa uji. Prediksi toksisitas dilakukan menggunakan perangkat lunak ADMET predictor dan QSAR Toolbox. Prediksi toksisitas dan hasil <em>docking</em> menunjukkan bahwa asam monakolin L menunjukkan aktivitas antikolesterol yang baik terhadap HMG KoA reduktase; pigmen monaskin menunjukkan aktivitas antikanker yang selektif terhadap reseptor estrogen beta; dan keduanya diprediksi aman. Prediksi toksisitas senyawa monakolin dan pigmen <em>Monascus </em>sp. menunjukkan terdapat 7 senyawa monakolin yaitu 3-hidroksi-3,5-dihidromonakolin L<em>, </em>asam dihidromonakolin L<em>, </em>monakolin L<em>, </em>asam monakolin J<em>, </em>monakolin J, asam monakolin L , monakolin M, dan 5 pigmen <em>Monascus</em> sp<em>. </em>yaitu ankaflavin, monaskin, monaskopiridin A, monaskopiridin B dan <em>monascuspiloin</em> yang dinyatakan tidak toksik. Tujuh pigmen <em>Monascus</em> sp<em>.</em> yang terdiri dari monankarin A, monankarin B, monankarin<em> </em>C,<em> </em>monankarin D,<em> </em>monankarin E, monankarin F,<em> </em>dan monasfluol A<em> </em>bersifat<em> </em>positif mutagen, karsinogen dan toksik terhadap reproduksi. Hasil penelitian ini berpotensi dapat diaplikasikan untuk desain dan pengembangan obat antikolesterol dan antikanker.</p><p><strong>In Silico Study of Secondary Metabolites of <em>Monascus </em>sp<em>.</em> as A Candidate for Anticholesterol and Anticancer Drugs.</strong> The fungus <em>Monascus </em>sp<em>.</em> has traditionally been used to prepare red fermented rice (angkak) as a natural food colorant, food preservative or medicinal agent. Recently, it has become a popular dietary supplement due to many of its bioactive constituents such as monacolin compounds, pigments, and dimerumic acid, etc. These functional constituents also had been deemed to be provided with various health benefits. This research aims to find secondary metabolites of monacolin compounds with antihypercholesterolemic effect, <em>Monascus</em> sp. pigment with anticancer effect on breast cancer, and predict their toxicity through in silico study. The studied compounds consist of 14 monacolin compounds and 33 <em>Monascus</em> sp. pigments. HMG CoA (3-hydroxy-3-methylglutaryl Coenzyme A) reductase protein was used as antihypercholesterolemic receptor in which estrogen alfa, estrogen beta, and aromatase were used as anticancer receptors. AutoDock docking software was used to analyze structural complexes of the receptors with studied compounds. Toxicity prediction was done using ADMET predictor and QSAR Toolbox softwares. Toxicity prediction and docking results revealed that monacolin L acid exhibits good anticholesterol activity towards HMG CoA reductase; monascin pigment exhibits selective anticancer activity towards estrogen beta receptor; and both of them were predicted to be safe. Toxicity prediction of studied compounds showed that 7 monacolin compounds which are 3-hydroxy-3,5-dihydromonakolin L, dihydromonacolin L acid, monacolin L, monacolin J acid, monacolin J, monacolin L acid, monacolin M and 5 <em>Monascus </em>sp. pigments which are ankaflavin, monascin, monascopyridine A, monascopyridine B dan monascuspiloin are not toxic. Seven Monascus sp. pigments which are monankarin A, monankarin B, monankarin C, monankarin D, monankarin E, monankarin F and monasfluol A are mutagenic, carcinogenic and also reprotoxic. The research results could be useful for the design and development of the anticholesterol and anticancer drugs.</p>

In Silico Study of Structural and Geometrical Requirements of Natural Sesquiterpene Lactones with Trypanocidal Activity

2013 ◽  
Vol 13 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
L. Fabian ◽  
V. Sulsen ◽  
F. Frank ◽  
S. Cazorla ◽  
E. Malchiodi ◽  
...  
Keyword(s):  
In Silico ◽  
Sesquiterpene Lactones ◽  
Trypanocidal Activity ◽  
In Silico Study

In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

2020 ◽  
Vol 17 (1) ◽  
pp. 40-50
Author(s):  
Farzane Kargar ◽  
Amir Savardashtaki ◽  
Mojtaba Mortazavi ◽  
Masoud Torkzadeh Mahani ◽  
Ali Mohammad Amani ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Alpha Helix ◽  
In Silico Analysis ◽  
Glycogen Storage ◽  
Docking Studies ◽  
Random Coil ◽  
Special Topic ◽  
Industrial Biotechnology ◽  
In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

In Silico Study of Ethylene Biosynthesis: Seeking New Effectors of ACC Synthase and ACC Oxidase

2016 ◽  
Vol 11 (3) ◽  
pp. 346-356
Author(s):  
Nada Ayadi ◽  
Sarra Aloui ◽  
Rabeb Shaiek ◽  
Oussama Rokbani ◽  
Faten Raboud ◽  
...  
Keyword(s):  
In Silico ◽  
Acc Oxidase ◽  
Acc Synthase ◽  
Ethylene Biosynthesis ◽  
In Silico Study

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Ebru Zeytün ◽  
Mehlika D. Altıntop ◽  
Belgin Sever ◽  
Ahmet Özdemir ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
In Silico ◽  
K562 Cell ◽  
Kinase Inhibitors ◽  
K562 Cell Line ◽  
Cytotoxic Effects ◽  
Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases

2020 ◽  
Vol 20 ◽  
Author(s):  
Trinath Chowdhury ◽  
Gourisankar Roymahapatra ◽  
Santi M. Mandal
Keyword(s):  
Rna Polymerase ◽  
Viral Entry ◽  
In Silico ◽  
Rna Dependent Rna Polymerase ◽  
Replication Complex ◽  
In Silico Study ◽  
Life Threatening ◽  
In Vivo Analysis ◽  
3Cl Protease

Background: COVID-19 is a life threatening novel corona viral infection to our civilization and spreading rapidly. Terrific efforts are generous by the researchers to search for a drug to control SARS-CoV-2. Methods: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Results: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also perform the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). Conclusion: In host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast invitro to in-vivo analysis towards development of therapeutics against SARS-CoV-2.

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