In Silico and in Vitro Evaluation of Deamidation Effects on the Stability of the Fusion Toxin DAB389IL-2

Background: DAB389IL-2 (Denileukin diftitox) as an immunotoxin is a targeted pharmaceutical protein and is the first immunotoxin approved by FDA. It is used for the treatment of various kinds of cancer such as CTCL lymphoma, melanoma, and Leukemia but among all of these, treatment of CTCL has special importance. DAB389IL-2 consists of two distinct parts; the catalytic domain of Diphtheria Toxin (DT) that genetically fused to the whole IL-2. Deamidation is the most important reaction for chemical instability of proteins occurs during manufacture and storage. Deamidation of asparagine residues occurs at a higher rate than glutamine residues. The structure of proteins, temperature and pH are the most important factors that influence the rate of deamidation. Methods: Since there is not any information about deamidation of DAB389IL-2, we studied in silico deamidation by Molecular Dynamic (MD) simulations using GROMACS software. The 3D model of fusion protein DAB389IL-2 was used as a template for deamidation. Then, the stability of deamidated and native form of the drug was calculated. Results: The results of MD simulations were showed that the deamidated form of DAB389IL-2 is more unstable than the normal form. Also, deamidation was carried by incubating DAB389IL-2, 0.3 mg/ml in ammonium hydrogen carbonate for 24 h at 37o C in order to in vitro experiment. Conclusion: The results of in vitro experiment were confirmed outcomes of in silico study. In silico and in vitro experiments were demonstrated that DAB389IL-2 is unstable in deamidated form.

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Triptolide is a Promising Therapeutic Approach in Treating Thyroid Cancer Based on in silico and in vitro Experiment

Drug Design Development and Therapy ◽

10.2147/dddt.s322502 ◽

2021 ◽

Vol Volume 15 ◽

pp. 4275-4287

Author(s):

Fang Wang ◽

Shu-Jing An ◽

Yirong Yin ◽

Juan-Juan Li ◽

Chun-Hui Sun ◽

...

Keyword(s):

Thyroid Cancer ◽

In Silico ◽

Therapeutic Approach ◽

Vitro Experiment ◽

In Vitro Experiment ◽

Promising Therapeutic Approach

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In vitro and In silico Evaluation of Structurally Diverse Benzyl-pyrrolidine-3-ol Analogues as Apoptotic Agents via Caspase Activation

Acta Chimica Slovenica ◽

10.17344/acsi.2021.6684 ◽

2021 ◽

Vol 68 (3) ◽

pp. 667-682

Author(s):

Tahira Naqvi ◽

Asif Amin ◽

Shujat Ali ◽

Mohsin Y. Lone ◽

Nadeem Bashir ◽

...

Keyword(s):

Cell Lines ◽

In Silico ◽

Caspase 3 ◽

Human Cancer ◽

Md Simulations ◽

Human Cancer Cell Lines ◽

Lead Compounds ◽

Model Protein ◽

The Stability

The activation of caspases is central to apoptotic process in living systems. Defects in apoptosis have been implicated with carcinogenesis. Need to develop smart agents capable of inducing apoptosis in tumor cells is obvious. With this motive, diversity oriented synthesis of 1-benzylpyrrolidin-3-ol analogues was envisaged. The multi component Ugi reaction synthesized library of electronically diverse analogues was explored for cytotoxic propensity towards a panel of human cancer cell lines at 10 μM. The lead compounds exhibit a selective cytotoxicity towards HL-60 cells as compared to cell lines derived from solid tumors. Besides, their milder cytotoxic effect on non-cancerous cell lines reaffirm their selective action towards cancer cells only.The lead molecules were tested for their ability to target caspase-3, as a vital protease triggering apoptosis. The lead compounds were observed to induce apoptosis in HL-60 cells around 10 μM concentration. The lead compounds exhibited various non-covalent supra type interactions with caspase-3 key residues around the active site. The binding ability of lead compounds with caspase-3 was studied via molecular docking and molecular dynamic (MD) simulations. MD simulations indicated the stability of compound-caspase-3 complex throughout the 50 ns simulation run. The stability and bio-availability of the lead compounds under physiological conditions was assessed by their interaction with Bovine Serum Albumin (BSA) as model protein. BSA interactions of lead compounds were studied by various bio-physical methods and further substantiated with in silico MD simulations.

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Identification of Benzothiazole‒Rhodanine Derivatives as α-Amylase and α-Glucosidase Inhibitors: Design, Synthesis, In-silico and In-Vitro Analysis

10.21203/rs.3.rs-954943/v2 ◽

2021 ◽

Author(s):

Mahendra Gowdru Sriniv ◽

Natasha Naval Aggarwal ◽

Banylla Felicity Dkhar Gatphoh ◽

Madan Kumar S ◽

Kannika B.R. ◽

...

Keyword(s):

In Silico ◽

Md Simulations ◽

Accessible Surface Area ◽

Solvent Accessible Surface Area ◽

Design Synthesis ◽

Glucosidase Inhibitors ◽

Accessible Surface ◽

The Stability ◽

Vitro Analysis

Abstract In search for possible antidiabetic agents, a new series of Benzothiazole-Rhodanine derivatives (A1-10) have been synthesized and characterized by spectral data(IR, 1H-NMR, C13-NMR,and HR-MS).All the designed compounds were subjected to In-silico studies using Schrodinger softwareand evaluated for In-vitro antidiabetic activityby α-amylase and α-glucosidase inhibitory assays.Among the tested compoundsA5, A6 and A9 showed good activity when compared to the standard Acarbose. Also, Molecular dynamic (MD) simulations were conducted to evaluate the stability of the ligand-protein complex by the calculation of the root mean of square deviation (RMSD), root mean square fluctuation (RMSF), and solvent accessible surface area (SASA).

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2,3-Dihydroquinazolin-4(1H)-one as a New Class of Anti-Leishmanial Agents: A Combined Experimental and Computational Study

Crystals ◽

10.3390/cryst12010044 ◽

2021 ◽

Vol 12 (1) ◽

pp. 44

Author(s):

Muhammad Sarfraz ◽

Chenxi Wang ◽

Nargis Sultana ◽

Humna Ellahi ◽

Muhammad Fayyaz ur Rehman ◽

...

Keyword(s):

In Silico ◽

Protein Complexes ◽

Computational Study ◽

Md Simulations ◽

Leishmania Species ◽

Trypanothione Reductase ◽

Pyridoxal Kinase ◽

New Class ◽

The Stability

Leishmaniasis is a neglected parasitic disease caused by various Leishmania species. The discovery of new protozoa drugs makes it easier to treat the disease; but, conventional clinical issues like drug resistance, cumulative toxicity, and target selectivity are also getting attention. So, there is always a need for new therapeutics to treat Leishmaniasis. Here, we have reported 2,3-dihydroquinazolin-4(1H)-one derivative as a new class of anti-leishmanial agents. Two derivatives, 3a (6,8-dinitro-2,2-disubstituted-2,3-dihydroquinazolin-4(1H)-ones) and 3b (2-(4-chloro-3-nitro-phenyl)-2-methyl-6,8-dinitro-2,3-dihydro-1H-quinazolin-4-one) were prepared that show promising in silico anti-leishmanial activities. Molecular docking was performed against the Leishmanial key proteins including Pyridoxal Kinase and Trypanothione Reductase. The stability of the ligand-protein complexes was further studied by 100 ns MD simulations and MM/PBSA calculations for both compounds. 3b has been shown to be a better anti-leishmanial candidate. In vitro studies also agree with the in-silico results where IC50 for 3a and 3b was 1.61 and 0.05 µg/mL, respectively.

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Effect of hydrophobically modified PEO polymers (PEO-dodecyl) on oil/water microemulsion properties: in vitro and in silico investigations

RSC Advances ◽

10.1039/d0ra09804c ◽

2021 ◽

Vol 11 (12) ◽

pp. 7059-7069

Author(s):

M. Khatouri ◽

R. Ahfir ◽

M. Lemaalam ◽

S. El Khaoui ◽

A. Derouiche ◽

...

Keyword(s):

Integral Equations ◽

In Silico ◽

Md Simulations ◽

Hydrophobically Modified ◽

Oil Water

In this work, we study the effect of grafted PEO-dodecyl co-polymers on the decane/water microemulsions properties. For this purpose, we combined the MD simulations, the OZ integral equations resolved using the HNC closure, and SANS experiments.

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