scholarly journals Synthesis, Antimicrobial Study, and Molecular Docking Simulation of 3,4-Dimethoxy-β-Nitrostyrene Derivatives as Candidate PTP1B Inhibitor

2020 ◽  
Vol 88 (3) ◽  
pp. 37
Author(s):  
Salman Alfarisi ◽  
Mardi Santoso ◽  
Alfinda Novi Kristanti ◽  
Imam Siswanto ◽  
Ni Nyoman Tri Puspaningsih
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Metabolic Diseases ◽  
Tyrosine Phosphatase ◽  
Docking Simulation ◽  
Docking Study ◽  
Negative Regulator ◽  
Potential Candidate ◽  
Molecular Docking Study ◽  
Cell Functions

A derivative series of 3,4-dimethoxy-β-nitrostyrene was synthesized through nitroaldol reaction, including a new compound of 3,4-ethylenedioxy-β-bromo-β-nitrostyrene. The antimicrobial activity effect of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking study was also performed to obtain information about their interactions with protein tyrosine phosphatase 1B (PTP1B). The active residues of cysteine-215 and arginine-221 of PTP1B play a key role in signaling pathways that regulate various microorganism cell functions. It also acts as a negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. These derivatives exhibited potential antifungal activity. The studied compounds were also had potential as fragments to be PTP1B inhibitors by interacting with serine-216 and arginine-221 residues, according to their molecular docking. 3,4-Ethylenedioxy-β-methyl-β-nitrostyrene was the most successful potential candidate as a PTP1B inhibitor. However, further research is needed to investigate their potential for medicinal use.

scholarly journals Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma

2020 ◽  
Vol 32 (12) ◽  
pp. 3079-3086
Author(s):  
K. Sarker ◽  
A. Ghosh ◽  
S. Mishra ◽  
A. Saha ◽  
S. Sen
Keyword(s):  
Multiple Myeloma ◽  
Molecular Docking ◽  
Carboxylic Acid ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
Docking Study ◽  
Potential Candidate ◽  
Molecular Docking Study ◽  
Antiangiogenic Activity

A series of N-(4-methoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed as bioisosteres of a major metabolite of thalidomide, i.e., N-(o-carboxybenzoyl)-D,L-glutamic acid. Compounds 2b, 2d, 2f, 2i and 2k exhibited anticancer activity on multiple myeloma (RPMI 8226) by MTS assay and were tested for primary antiangiogenic activity on HUVEC cell line by MTT assay. Compound 2f was excluded from further study as it was found to be cytotoxic to normal epithelial cells. 2b, 2d, 2i and 2k were found to have primary antiangiogenic activity along with low cytotoxicity on normal vero cells in MTT assay indicating selective cytotoxicity towards highly angiogenic multiple myeloma. Antiproliferative assay of compounds 2b, 2d, 2i and 2k on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 2b calculated the binding energy -89.78 kcal/mol and displayed five hydrogen bonds with critical amino acid residues. The compounds are potential candidate drugs for advanced investigations.

Acetogenins Exhibit Potential BCL-XL Inhibitor for the Induction of Apoptosis in the Molecular Docking Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Noraziah Nordin ◽  
Kaynat Khimani ◽  
Mohd Faiz Abd Ghani
Keyword(s):  
Molecular Docking ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Properties ◽  
Vital Role ◽  
Molecular Docking Study ◽  
Good Target ◽  
Induction Of Apoptosis

Background: Anti-apoptotic protein BCL-XL plays a vital role in tumorigenesis and cancer chemotherapy resistance, resulting in a good target for cancer treatment. Understanding the function of BCL-XL has driven the progression of a new class of cancer drugs that can mimic its natural inhibitors, BH3-only proteins to trigger apoptosis. This mimicking is initiated through acetogenins due to their excellent biological properties. Acetogenins which can be isolated from Annonaceae plants, have a unique structure along with several oxygenated functionalities. Objective: Based on their biological capability, various acetogenins were studied in the present study and compared alongside with ABT-737 on molecular docking. Methods: The docking simulation of acetogenins was performed using AutoDock Vina software. Results: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than – 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11) and isoannonacin-10-one A (18). Conclusion: These findings indicated that some acetogenins could represent a new potential BCL-XL inhibitor which could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.

scholarly journals Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1247
Author(s):  
Kyeong Lee ◽  
Hossam Nada ◽  
Hyun Jung Byun ◽  
Chang Hoon Lee ◽  
Ahmed Elkamhawy
Keyword(s):  
Molecular Docking ◽  
Combinatorial Library ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Hybrid Approach ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Hit Identification

EphB3 is a major key player in a variety of cellular activities, including cell migration, proliferation, and apoptosis. However, the exact role of EphB3 in cancer remains ambiguous. Accordingly, new EphB3 inhibitors can increase the understanding of the exact roles of the receptor and may act as promising therapeutic candidates. Herein, a hybrid approach of structure-based design and virtual combinatorial library generated 34 quinazoline sulfonamides as potential selective EphB3 inhibitors. A molecular docking study over EphB3 predicted the binding affinities of the generated library, and the top seven hit compounds (3a and 4a–f), with GlideScore ≥ −6.20 Kcal/mol, were chosen for further MM-GBSA calculations. Out of the seven top hits, compound 4c showed the highest MM-GBSA binding free energy (−74.13 Kcal/mol). To validate these predicted results, compounds 3a and 4a–f were synthesized and characterized using NMR, HRMS, and HPLC. The biological evaluation revealed compound 4c as a potent EphB3 inhibitory lead (IC50 = 1.04 µM). The screening of 4c over a mini-panel of kinases consisting of EGFR, Aurora A, Aurora B, CDK2/cyclin A, EphB1, EphB2, EphB4, ERBB2/HER2, and KDR/VEGFR2, showed a promising selective profile against EphB3 isoform. A dose-dependent assay of compound 4c and a molecular docking study over the different forms of EphB provided insights into the elicited biological activities and highlighted reasonable explanations of the selectivity.

scholarly journals GLYCOGEN SYNTHASE KINASE-3 BETA PROTEIN INHIBITION BY SELECTED PHYTOCOMPOUNDS IN SILICO

2016 ◽  
Vol 10 (1) ◽  
pp. 87
Author(s):  
Vanitha Varadharaj ◽  
Naresh Kandakatl
Keyword(s):  
Molecular Docking ◽  
Glycogen Synthase ◽  
Protein A ◽  
Experimental Studies ◽  
Docking Simulation ◽  
Docking Study ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Molecular Docking Study ◽  
Gsk 3Β

ABSTRACTObjectives: Bioactive phytocompounds are a rich source of chemopreventive substance. In the present investigation, docking study was performedfor the selected bioactive phytocompounds such as oleanolic acid, ecdysterone, betaine, stigmasterol acetate, and cinnamic acid to evaluate theiraffinity to glycogen synthase kinase-3 beta (GSK-3β) protein, a wound-healing biomarker. 2-chloro-5-[4-(3-chloro-phenyl)-2, 5-dioxo-2,5-dihydro-1hpyrrol-3-ylamino]-benzoicacid wasused as an inhibitorforGSK-3βwith minimum binding energy(−31.5 kcal/mol).Methods: Molecular docking study was conducted using AutoDock 4.2 version and the visualization result using Discover Studio 4.5.Results: The docking analysis ranked the selected phytocompounds that have high theoretical scores to bind to the proteins. The binding mode of thephytocompounds that bound to all the target proteins with high affinity was studied. The simulation demonstrated that the protein-ligand complexstabilized by multiple hydrogen bonds (H-bonds) was preferentially formed at the catalytic site. The results highlighted in this study reveals thatamong the selected lead phytocompounds that docked into the active site of GSK-3β, ecdysterone showed acceptable 6 H-bond interactions withresidues LYS85, TYR134, ARG141, GLN185, ASP200, PRO136 when compared to the reference compound with 5 H-bond interactions.Conclusion: Thus, based on the docking score ecdysterone could be considered as a novel compounds that can be used for experimental studies forthe inhibition of GSK-3β kinase. These results can be helpful for further design of novel GSK-3β inhibitors.Keywords: Phytocompounds, Molecular docking, Simulation, Receptor, Ligand, Inhibition.

scholarly journals Ethanolic Extract of Hedyotis corymbosa and Its Combination with 5-FU Inhibit Cyclin D Expression on WiDr Colorectal Cancer Cell

2017 ◽  
Vol 7 (1) ◽  
pp. 25 ◽  
Author(s):  
Argandita Meiftasari ◽  
Januar Caesar W.P. ◽  
Annisa Novarina ◽  
Julika Yovi W. ◽  
Riris Istighfari Jenie
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Ursolic Acid ◽  
Cancer Cell ◽  
Docking Simulation ◽  
Ethanolic Extract ◽  
Docking Study ◽  
Antiproliferative Effect ◽  
Cyclin D ◽  
Molecular Docking Study

Hedyotis corymbosa has been used for long time as an important component in several folklore medicine formula to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, Hedyotis corymbosa ethanolic extract (HEE) which contain ursolic acid reported to inhibit CRC growth via induction of cancer cell apop­tosis and blocked the cell cycle, preventing G1 to S progression where cyclin D highly espressed in this phase. 5-fluorouracil (5FU), the first line chemotherapy of colorectal cancer have had resistence and possessed several side effects such as neutropenia, immunosuppression, diarrhea, and also constipation. Therefore, the aim of this research is to conduct the antiproliferative effect and molecular analysis of HEE and its combination with 5FU. Molecular docking study was also done to approach the specific protein target of the compound. Antiproliferative effect was conducted by MTT assay, while cyclin D expression  was examined by immunofluorescence. The proliferative effect showed that both HEE and 5-FU had cytotoxic effect with IC50 value of 65 µg/mL and 90 µM respectively, meanwhile the combination of HEE and 5FU have synergism effect with CI = 0.48 on dose HEE = 22 µg/mL and 5FU= 6.25 µM. Immunofluorescence assay showed HEE and its combination with 5FU suppressed the expression of cyclin D. From molecular docking simulation, ursolic acid performed stable interaction with cyclin D. Our findings suggest that HEE may be an effective treat­ment for co-chemotherapic for 5-FU through inhibition of cyclin D expression.Keywords : Hedyotis corymbosa, 5-fluorouracil, colorectal cancer,  WiDr, cyclin D 

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