scholarly journals Synthesis, Characterization, Anti-Mycobacterial Evaluation and In-Silico Molecular Docking of Novel Isoxazole Clubbed Pyrimidine Derivatives

2021 ◽  
pp. 69-79
Author(s):  
Nagaraju Pappula ◽  
Ravichandra Sharabu
Keyword(s):  
Molecular Docking ◽  
Software Tool ◽  
Antitubercular Activity ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Lipinski’S Rule ◽  
Mycobacterium Tuberculosis H37rv ◽  
Lead Compounds ◽  
H37rv Strain ◽  
In Silico Molecular Docking

In the present research, we tend to ready a series of novel pyrimidine-linked isoxazole derivatives (11-20). The molecular structure and the elemental composition of these compounds were confirmed by spectroscopic studies and elemental analysis. MABA (Microplate alamar Blue Assay) assay was employed for assessing the antitubercular activity against the Mycobacterium tuberculosis H37Rv strain. Among the ten synthesized compounds, 18 and 20 showed excellent anti-tubercular activity than the reference (MIC-3.125 µg/ml) at 0.78 µg/mL. The compounds were found to possess good binding affinity than a standard against thymidylate kinase enzyme (PDB-1MRS) as evidenced by the molecular docking studies. Additionally, the bioactivity was conducted by Mol-inspiration software tool and the drug-likeness property was evaluated on Lipinski's rule of five by SCFBio online software. The lead compounds identified through these studies could be useful for the furtherance of the drug discovery process in the area of antitubercular research.

Synthesis and In-silico identification of new bioactive 1,3,4-oxadiazole tagged 2,3-dihydroimidazo[1,2-a]pyridine derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Bhagwat S. Jadhav ◽  
Vipul P. Purohit ◽  
Ramesh S. Yamgar ◽  
Rajesh S. Kenny ◽  
Suraj N. Mali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Pyridine Derivatives ◽  
Molecular Docking Studies ◽  
New Class ◽  
In Silico Molecular Docking

Background: Tuberculosis (TB) continues to be the most threatening cause of death in recent years. There is urgent need of search more potent, less toxic antitubercular agents. Methods: A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) was synthesized and screened invitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294. Results: Compound 4b displayed potent antitubercular activity at MIC 6.25 µg/mL. In-silico molecular docking studies were performed for evaluation of the binding patterns of compounds 4a-4e in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in- vitro antitubercular studies were in well agreement with the molecular docking studies. These newly synthesized compounds were found to have good ADMET profile. We also explored possible anticancer activity using in-silico methods. Conclusion: These results shows that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) are attracting new class of potent anti-TB targets as well as possible anticancer activity that worth additional opportunities for improvements.

scholarly journals Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Suhaib Shekfeh ◽  
Murad Abualhasan ◽  
Ahmad M. Eid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Alpha Amylase ◽  
In Vivo Evaluation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Lipase Enzyme ◽  
Lipinski’S Rule Of Five

AbstractCurrently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.

Novel Furan Coupled Quinoline Diamide Hybrid Scaffolds as Potent Antitubercular Agents: Design, Synthesis and Molecular Modelling

2020 ◽  
Vol 16 (4) ◽  
pp. 507-516
Author(s):  
Anantacharya Rajpurohit ◽  
Nayak D. Satyanarayan ◽  
Lokesh Pathak ◽  
Siva Ayyanar ◽  
Chidambaram R. Rishinaradamangalam ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Design Synthesis ◽  
Molecular Binding ◽  
H37rv Strain ◽  
Docking Program ◽  
Novel Drug

Background: A novel series of 2-[(2-[2-(furan-2-yl) quinolin-4-yl] carbonyl hydrazinyl) carbonyl] benzoic acid, -4-oxobut-2-enoic acid and -4-oxobutanoic acids were synthesized and screened for in vitro antitubercular activity. Objectives: In the present investigation, we describe the synthesis and biological screening of furan C-2 quinoline coupled diamides for antitubercular activity. Methods: The mycobacterium tuberculai testing was carried out by MABA method and molecular docking studies were done by open-source molecular docking program, Autovina, using Pyrx 0.8 interface. Results: The results revealed that the compounds inhibited the growth of H37Rv strain at concentrations as low as 1.6 to 12 µg/ml. Molecular binding of furan, quinoline and diamide (FQD) derivatives on five targets was good and these compounds fit very well within the binding domain of the target protein. Conclusion: The synthesized FQD derivatives exhibited moderate to good inhibition activity especially compounds 5f, 5b and 8a exhibited very good inhibition activity due to the presence of three different scaffolds, such as INH, phenyl ketobutyric acid and fluoroquinolines. Hybridized molecules might have multiple modes of action / inhibit more than one tubercular target and could pave way for novel drug discovery in the field of tuberculosis.

scholarly journals Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

2020 ◽  
Author(s):  
Dr. Divya Shaji
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Moringa Oleifera ◽  
Docking Studies ◽  
World Health ◽  
Lipinski’S Rule ◽  
Lead Compounds ◽  
Global Pandemic ◽  
Drug Lead ◽  
Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

scholarly journals Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

2020 ◽  
Author(s):  
Dr. Divya Shaji
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Moringa Oleifera ◽  
Docking Studies ◽  
World Health ◽  
Lipinski’S Rule ◽  
Lead Compounds ◽  
Global Pandemic ◽  
Drug Lead ◽  
Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

scholarly journals Design, Synthesis, Molecular Docking Studies and Antitubercular Evaluation of Hexahydroquinolin-2-yl Benzamide Derivatives

2021 ◽  
Vol 33 (8) ◽  
pp. 1923-1928
Author(s):  
N. Raghavendra Babu ◽  
G.S.N. Koteswara Rao ◽  
Rajasekhar Reddy Alavala ◽  
P.S. Lakshmi Soukya
Keyword(s):  
Molecular Docking ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Significant Activity ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Zebrafish Larvae ◽  
H37rv Strain ◽  
Target Dna ◽  
Benzamide Derivatives

A new series of hexahydroquinolin-2-yl benzamide derivatives (BZ1-10) were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR and ESI-MS spectra and also subjected for molecular docking studies with the target DNA gyrase enzyme (PBD ID: 4B6C). The molecular docking results of synthesized derivatives indicated the best docking score of -5.105 and -5.02 for BZ9 and BZ4, respectively. All the synthesized compounds were screened for antitubercular activity against H37RV strain, among all, two compounds exhibited significant activity at 12.5 μg/mL and 25 μg/mL concentrations. Thus, the MIC values are in between range of 12.5 and 6.25 μg/mL concentrations. The teratogenicity assay of synthesized compounds was performed in zebrafish larvae, out of the ten compounds, BZ4, BZ6 and BZ8 compounds were found to safer at 0.5 μM concentration without any abnormalities.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Design, Synthesis and Antitubercular Evaluation of New Benzimidazole Scaffolds

2021 ◽  
Vol 18 (4) ◽  
pp. 375-383
Author(s):  
Smriti Yadav ◽  
Bharath Kumar Inturi ◽  
Shrinidhi B.R ◽  
Pooja H.J ◽  
Neenu Ganesh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Lines ◽  
Normal Cell ◽  
Acyl Carrier Protein ◽  
Antitubercular Activity ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Chemical Library ◽  
Activity Data ◽  
Mycobacterium Tuberculosis H37rv

Background: To overcome one of the resistance mechanisms of Isoniazid (INH), there is a need for an antitubercular agent that can inhibit InhA enzyme by circumventing the formation of INH-NAD+ adduct. Objective: The objective of the study is the development of novel antitubercular agents that target Mycobacterium tuberculosis InhA (Enoyl Acyl Carrier Protein Reductase). Methods: A small-molecule chemical library was used for the identification of the novel InhA inhibitors using primary screening and molecular docking studies followed by the scaffold hopping approach. The designed molecules, 2-(2-(hydroxymethyl)-1H- benzo[d] imidazole-1-yl)- N- substituted acetamides were synthesized by reacting (1H- benzo[d]imidazole -2-yl)methanol with appropriate 2-chloro-N-substituted acetamides / dialkylamino carbonyl chlorides respectively in good yields (42-65%). The antitubercular activity of synthesized compounds was determined by Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37Rv strain. The selected compounds were screened for cytotoxicity on normal cell lines. Results: The antitubercular activity data revealed that the 4-chlorophenyl substituted derivative (3b) showed good MIC value at 6.25 μg/mL and, dimethylacetamide substituted derivative (3i) showed MIC at 25 μg/mL among the tested compounds. The substitution of dimethylacetamide (3i) group on the 1st position of benzimidazole has good antitubercular activity (25μg/mL) in comparison to the diethyl acetamide group (3j, 100μg/mL). Conclusion: The antitubercular activity data indicated that the tested compounds exhibited well to moderate inhibition of the H37Rv strains. The compounds (3b) with electronegative substitution on the phenyl moiety exhibited better antitubercular activity than that of the other substitutions. The active compounds have displayed a good safety profile on normal cell lines.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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