scholarly journals Pass and Swiss ADME collaborated in silico docking approach to the synthesis of certain pyrazoline spacer compounds for dihydrofolate reductase inhibition and antimalarial activity

2018 ◽  
Vol 13 (1) ◽  
pp. 23 ◽  
Author(s):  
Krishnakumar Lohidakshan ◽  
Manju Rajan ◽  
Andhale Ganesh ◽  
Mathew Paul ◽  
Jithu Jerin
Keyword(s):  
In Silico ◽  
Antimalarial Activity ◽  
Video Clip ◽  
Acid Hydrazide ◽  
Building Blocks ◽  
Docking Study ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Docking Approach

<p class="Abstract">New series of pyrazoline spacer compounds were prepared by the reaction between benzimidazole chalcones and (2-methyl-5-nitro-imidazole-1-yl)-acetic acid hydrazide by the sensible use of Michael addition. The building blocks used for the synthesis of pyrazoline derivatives were opted by using virtual screening by molinspiration search engine. The hypothetically resulted pyrazoline spacer compounds from this list are checked for their reliability on other in silico drug designing online web services like PASS online bioactivity, Swiss ADME predictor. The docking study on final four pyrazoline compounds was carried out using Accelrys Discovery Studio 3.5. These synthesized compounds were, later, characterized with the help of UV, IR, mass and <sup>1</sup>H NMR techniques. These compounds were further screened for their in vitro antimalarial effect. The PASS, Swiss ADME assisted docking approach and the use of combo heterocyclic ring with pyrazoline scaffold were found to be beneficial to derive and synthesize effective antimalarial agents in the present study.</p><p class="Abstract"><strong>Video Clip of Methodology</strong>:</p><p class="Abstract">6 min 20 sec:   <a href="https://www.youtube.com/v/RWwaZuG1j9E">Full Screen</a>   <a href="https://www.youtube.com/watch?v=RWwaZuG1j9E">Alternate</a></p>

In vitro evaluation and molecular dynamics, DFT guided investigation of antimalarial activity of ethnomedicinally used Coptis teeta Wall

2021 ◽  
Vol 24 ◽  
Author(s):  
Ashis Kumar Goswami ◽  
Hemanta Kumar Sharma ◽  
Neelutpal Gogoi ◽  
Ankita Kashyap ◽  
Bhaskar Jyoti Gogoi
Keyword(s):  
Molecular Dynamics ◽  
In Silico ◽  
Density Functional ◽  
Antimalarial Activity ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Discovery Studio ◽  
North East ◽  
Silico Analysis

Background: Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of north east India. Objective: In this study, the anti malarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification via in silico study. Method: On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta. Results: The IC50 of the methanol extract of Coptis teeta 0.08 µg/ml in 3D7 strain and 0.7 µg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the band gap energy of noroxyhydrastinine was found to be 0.186 Ha indicating a favourable interaction. Conclusion: The in silico analysis as an addition to the in vitro results provide strong evidence of noroxyhydrastinine as an anti malarial agent.

scholarly journals Design, Synthesis, and Preclinical Bio Evaluation of Chemical Conjugates Derived from Phytophenols and Nitrobenzoate as First Plausible Inhibitors of MPO Useful in CVD Treatment

2020 ◽  
Vol 11 (4) ◽  
pp. 11630-11652
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Radical Scavenging ◽  
Building Blocks ◽  
Xrd Analysis ◽  
Positive Control ◽  
In Silico Docking ◽  
Lead Compounds ◽  
Chemistry Research

Phytophenols are important phytonutrients and useful building blocks for medicinal chemistry research. Designed conjugates derived from phytophenols and nitrobenzoate were evaluated for MPO inhibition using in-silico docking and ADMET studies. Hit to lead compounds were prepared and confirmed by NMR, mass, and single-crystal XRD analysis. Based on the in-silico study, an in-vitro MPO inhibition assay was performed and identified two best compounds 1 and 2 (MPO-IC50 value is 12.88 and 14.97 µM respectively) lead molecules. An ex-vivo anti-inflammatory study was performed with human erythrocyte hemolysis using coagulated blood cells with increasing concentration (20 to 100 µM) of the lead molecules. The activity range was found to be ~85% and ~75% for compounds 1 and 2, respectively. DPPH and ABTS radical scavenging assays of the lead molecules were compared with ascorbic acid (positive control). MTT-cell line study shows that lead compounds were non-toxic even at higher concentrations. The outcome of this study demonstrated that conjugates 1 and 2 be considered potent inhibitors of MPO and useful cardiovascular therapeutic agents.

1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors.

2020 ◽  
Vol 21 ◽  
Author(s):  
Elizabeth Eldhose ◽  
Kaviarasan Lakshmanan ◽  
Praveen T. Krishnamurthy ◽  
Kalirajan Rajagopal ◽  
Manal Mohammed ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Activities ◽  
Docking Study ◽  
Binding Mode ◽  
Oral Toxicity ◽  
Standard Drug ◽  
In Silico Docking

Background: 1,3,4-thiadiazolo pyrimidine is a lead molécule which is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. Objective: The objective of the study was to synthesize series of 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] - [1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivative and evaluated for their possible in vitro and in vivo anticancer activity. Methods: Herein we report the synthetic scheme which was followed for the preparation of a series of title compounds B1- B9 is outlined in the scheme 1. The intermediate 5-[(naphthalen-2- yloxy)methyl]-1,3,4-thiadiazolo-2-amine was prepared by heating 2-naphthoxyacetic acid and thiosemicarbazide in presence of phosphoryl chloride at a temperature of 65 - 750C. The obtained compound reacted with malononitrile and appropriate amount of aromatic and heteroaromatic aldehydes in refluxing ethanol yielded 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives (B1 – B9). The purity of synthesized compounds ensured by various spectral analysis. Results: In in-silico molecular docking studies compounds B3 and B9 show binding affinity like known PARP1 inhibitor olaparib. The cellular evaluation indicates that the anticancer activity of compounds B1, B3, B9 is significant when compared to standard drug (olaparib) against MDA-MB-232 cell line and compounds B3, B6, B7 are most active against MCF-7 cell lines. The most active compound B3 was subjected to acute oral toxicity studies by OECD 423 guidelines and in-vivo anti-cancer studies were carried out using DMBA induced model. Conclusion: The in-silico docking study of the newly synthesized compounds were performed, the results showed good binding mode in the active site of PARP1 enzyme. In-silico ADME properties of synthesized compounds were also studied and showed good drug like properties.

Identification of Major Compounds and α-Amylase and α-Glucosidase Inhibitory Activity of Rhizome of Musa balbisiana Colla: An In-vitro and insilico Study

2020 ◽  
Vol 23 ◽  
Author(s):  
Ananta Swargiary ◽  
Manita Daimari
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Docking Study ◽  
Cell Membrane Permeability ◽  
Musa Balbisiana ◽  
Discovery Studio ◽  
Postprandial Glycemia ◽  
Spectrophotometric Methods ◽  
Glucosidase Inhibitors

Background: α-Amylase and α-glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type 2 diabetes. Objectives: To evaluate the metallic content, major phytoconstituents, and α-amylase and α-glucosidase inhibitory activity of Musa balbisiana rhizome using in-vitro and in-silico methods. Materials and Methods: Heavy metal content was detected by AAS following standard protocol. Major phytochemicals of the plant were analysed by GC-MS technique. Enzyme inhibition study was carried out by UV/VIS spectrophotometric methods. The druglikeness and bioavailability properties of major compounds were carried out using computer-aided tools – SwissADME and ADMElab. Docking and visualization were performed in AutoDock vina and Discovery studio tools. Results: The study found that the fruits of M. balbisiana contain negligible amount toxic elements. GC-MS analysis showed five major compounds from the rhizome of M. balbisiana. In-vitro enzyme assays revealed strong α-amylase and αglucosidase inhibitory property of the plant. All the five compounds were predicted to have druglikeness property with high cell membrane permeability and bioavailability. The compounds were also predicted to have low to moderate toxicity property. The Docking study showed strong binding affinities of plant compounds with α-amylase and α-glucosidase. Out of five compounds, C5 showed best binding affinity with active pockets of α-amylase and α-glucosidase. Conclusion: The present in-vitro and in-silico study suggests the antihyperglycemic property of the rhizome of Musa balbisiana and possible candidate for therapeutic antidiabetic agent(s).

scholarly journals ANTICHOLINESTERASE ACTIVITY OF OCTA PEPTIDES RELATED TO HUMAN HISTATIN 8: IN-SILICO DRUG DESIGN AND IN-VITRO

2017 ◽  
Vol 10 (6) ◽  
pp. 115 ◽  
Author(s):  
Pandurangan Perumal ◽  
Mani Vasudevan ◽  
Sridevi Chigurupati ◽  
Manikandan Selvaraj
Keyword(s):  
In Silico ◽  
Potent Inhibitor ◽  
Docking Study ◽  
Ache Inhibitor ◽  
In Silico Docking ◽  
In Silico Drug Design ◽  
Ic50 Value ◽  
Ache Inhibitory Activity ◽  
Histatin 8

Objective: To evaluate the octapeptides related to human histatin 8 by in-silico and in-vitro studies.Method: Schrodinger, LLC and Ellman’s method.Results: The compound HH1 and HH2 was found to be potent docking score of −9.494 and −7.401 against acetylcholinesterase (AChE) enzyme. The IC50 value of HH1 and HH2 was found to be 0.39±0.28 and 0.78±0.15 μg/mL. However, these compounds are shown to be highly effective as compared with the control AChE inhibitor donepezil (0.065±0.0050 μg/mL).Conclusion: In-silico docking study was conducted for the designed octapeptides related to human histatin 8 against AChE enzyme shows significance binding affinity toward HH1 and HH2 peptides and the AChE inhibitory activity of octapeptides shown to be a highly potent inhibitor as compared with control donepezil.

scholarly journals Synthesis, Characterization, In-Silico Docking Study and In-Vitro AntiInflammatory Activities of Novel Chalcone Derivatives

2021 ◽  
Vol 3 (2) ◽  
pp. 1-6
Author(s):  
R Bharathi ◽  
◽  
N Santhi ◽  
Keyword(s):  
In Silico ◽  
Aromatic Aldehydes ◽  
Docking Study ◽  
Docking Studies ◽  
In Silico Docking ◽  
Therapeutic Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Important Activity

A series of chalcones were synthesised by condensation of appropriate acetophenones with appropriate aromatic aldehydes, and their anti-inflammatory activities were investigated. In comparison to standard drugs, some have been found to have important activity. In silico docking, tests on chalcones were shown to be more selective to COX-2. Further anti-inflammatory results were supported by docking studies with COX-2. The results from the anti-inflammatory and docking indicate that the synthesised compounds 3b, 3g and 3h can be seen as therapeutic drugs.

2,4-Dioxochroman Moiety Linked to 1,2,3-triazole Derivatives as Novel α-glucosidase Inhibitors: Synthesis, In vitro Biological Evaluation, and Docking Study

2020 ◽  
Vol 24 (17) ◽  
pp. 2019-2027 ◽  
Author(s):  
Marjan Mollazadeh ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Yousef Valizadeh ◽  
Afsaneh Zonouzi ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
In Silico ◽  
Click Reaction ◽  
Docking Study ◽  
Competitive Inhibitor ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Standard Drug ◽  
In Silico Docking ◽  
Glucosidase Inhibitors

In this study, a novel series of 2,4-dioxochroman-1,2,3-triazole hybrids 8a-l was synthesized by click reaction. These compounds were screened against α-glucosidase through in vitro and in silico evaluations. All the synthesized hybrids exhibited excellent α-glucosidase inhibition in comparison to standard drug acarbose. Representatively, 3-((((1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)amino)methylene)chroman-2,4- dione 8h with IC50 = 20.1 ± 1.5 μM against α-glucosidase, was 37-times more potent than acarbose. Enzyme kinetic study revealed that compound 8h was a competitive inhibitor against α-glucosidase. In silico docking study on chloro derivatives 8h, 8g, and 8i were also performed in the active site of α -glucosidase. Evaluations on obtained interaction modes and binding energies of these compounds confirmed the results obtained through in vitro α-glucosidase inhibition.

scholarly journals Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 751 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Mohammed Al-Azri ◽  
Majid Khan ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Dissociation Constants ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Active Compounds ◽  
In Silico Docking ◽  
In Silico Studies ◽  
First Time

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2‒21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 μM. Compound 4 (IC50 = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 μM), 5 (IC50 = 20.9 ± 0.05 μM) and 3 (IC50 = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.

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