Unveiling the anti-tubercular properties of Biscoumarins, through Biological Evaluation and Docking Studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Poornima Acharya ◽  
M. M. V. Ramana ◽  
Manish Upadhyay ◽  
Ganesh Pavale
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Neutrophil Function ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Assay Method ◽  
Binding Interaction ◽  
H37rv Strain ◽  
Function Test

Background: Biscoumarin scaffolds are known for their promising pharmacological properties. These compounds have not been studied for their activity against tuberculosis strains. Objective: Unveil the antitubercular properties of biscoumarin scaffolds. Methods: Biscoumarin derivatives (3a-3l) were synthesized using lemon juice as a catalyst and were investigated for their in-vitro anti-tubercular activity against H37Rv strain of Mycobacterium tuberculosis using Microplate Alamar Blue Assay Method (MABA). Their binding interaction was investigated by Molecular Docking Studies using InhA with PDB-ID: 2NSD as target receptors in H37Rv strain of Mycobacterium tuberculosis. These derivatives (3a-3l) were subjected to neutrophil function test. Results: The results revealed that compounds 3b, 3c, 3d, 3f, 3i, 3j showed excellent activity with MIC 1.6 µg/mL. Molecular docking interactions for their antitubercular activity proved that the derivatives (3a-3l) can easily bind into the pockets of InhA enzyme. Neutrophil function test signified that they exhibit moderate neutrophil functions assuring that they do not harm the functioning of Neutrophils. Conclusion: These studies have awakened the property of Biscoumarins as promising anti-tubercular scaffolds.

scholarly journals in silico Design, ADME Prediction, Molecular Docking, Synthesis of Novel Triazoles, Indazoles & Aminopyridines and in vitro Evaluation of Antitubercular Activity

2020 ◽  
Vol 32 (11) ◽  
pp. 2713-2721
Author(s):  
S. Triveni ◽  
C. Naresh Babu ◽  
E. Bhargav ◽  
M. Vijaya Jyothi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Drug Design ◽  
In Silico ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Luciferase Reporter ◽  
Assay Method ◽  
Adme Prediction

To design and synthesize novel triazoles, indazoles and aminopyridines from various (thiophene-2-yl)prop-2-en-1-one derivatives as antitubercular leads by in silico and in vitro methods. in silco Drug design, ADME prediction and molecular docking studies were performed to assess drug likeliness and antitubercular potential of all 30 novel triazoles, indazoles and aminopyridines. in silico Drug design studies revealed that the synthetic routes applied were appropriate according to the calculations of Swiss-ADME that measure synthetic accessibility. Most of the synthesized compounds found to have considerable binding score with enoyl ACP reductase enzyme of Mycobacterium tuberculosis. All the synthesized compounds were evaluated for antitubercular potential against Drug Resistant Mycobacterium tuberculosis H37Rv strain by Luciferase reporter assay method. Most of the synthesized compounds exhibited remarkable antitubercular potential against resistant strain.

scholarly journals Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

2020 ◽  
Author(s):  
Mohsinul Mulk Bacha ◽  
Humaira Nadeem ◽  
Shafiq Ur Rehman ◽  
Sadia Sarwar ◽  
Aqeel Imran ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Molecular Docking ◽  
Aldose Reductase ◽  
Diabetic Complications ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Aldehyde Reductase ◽  
Standard Drug ◽  
Molecular Docking Studies

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.

scholarly journals New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 178 ◽  
Author(s):  
Mahadev Patil ◽  
Anurag Noonikara-Poyil ◽  
Shrinivas D. Joshi ◽  
Shivaputra A. Patil ◽  
Siddappa A. Patil ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Growth Inhibition ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Bacterial Strains ◽  
Binding Interaction ◽  
Urea Derivatives ◽  
Molecular Docking Studies

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). Variable levels of interaction were observed for these urea derivatives. However, and of major importance, many of these molecules exhibited promising growth inhibition against Acinetobacter baumannii. In particular, to our delight, the adamantyl urea adduct 3l demonstrated outstanding growth inhibition (94.5%) towards Acinetobacter baumannii. In light of this discovery, molecular docking studies were performed in order to elucidate the binding interaction mechanisms of the most active compounds, as reported herein.

Evaluation of Antiplasmodial Potential of C2 and C8 Modified Quinolines: in vitro and in silico Study

2019 ◽  
Vol 15 (7) ◽  
pp. 790-800 ◽  
Author(s):  
Rakesh Kumar ◽  
Ritika Sharma ◽  
Inder Kumar ◽  
Pooja Upadhyay ◽  
Ankit Kumar Dhiman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Malaria Parasite ◽  
Resistance Index ◽  
Microtiter Plate ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Molecular Docking Studies ◽  
Human Red Blood Cells ◽  
Computational Molecular Docking

Background: Malaria remains a common life-threatening infectious disease across the globe due to the development of resistance by Plasmodium parasite against most antimalarial drugs. The situation demands new and effective drug candidates against Plasmodium. Objectives: The objective of this study is to design, synthesize and test novel quinoline based molecules against the malaria parasite. Methods: C2 and C8 modified quinoline analogs obtained via C-H bond functionalization approach were synthesized and evaluated for inhibition of growth of P. falciparum grown in human red blood cells using SYBR Green microtiter plate based screening. Computational molecular docking studies were carried out with top fourteen molecules using Autodoc software. Results: The biological evaluation results revealed good activity of quinoline-8-acrylate 3f (IC50 14.2 µM), and the 2-quinoline-α-hydroxypropionates 4b (IC50 6.5 µM), 4j (IC50 5.5 µM) and 4g (IC50 9.5 µM), against chloroquine sensitive Pf3D7 strain. Top fourteen molecules were screened also against chloroquine resistant Pf INDO strain and the observed resistant indices were found to lie between 1 and 7.58. Computational molecular docking studies indicated a unique mode of binding of these quinolines to Falcipain-2 and heme moiety, indicating these to be the probable targets of their antiplasmodial action. Conclusion: An important finding of our work is the fact that unlike Chloroquine which shows a resistance Index of 15, the resistance indices for the most promising molecules studied by us were about one indicating equal potency against drug sensitive and resistant strains of the malaria parasite.

Design, Synthesis and Biological Evaluation of Anti-tuberculosis Agents based on Bedaquiline Structure

2020 ◽  
Vol 16 (5) ◽  
pp. 703-714
Author(s):  
Chengjun Wu ◽  
Jinghan Luo ◽  
Mengtong Wu ◽  
Fanzhen Meng ◽  
Zhiqiang Cai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Atp Synthase ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Mycobacterium Tuberculosis H37rv ◽  
Inhibitory Activities ◽  
Relationship Of

Background: Bedaquiline is a novel anti-tuberculosis drug that inhibits Mycobacterial ATP synthase. However, studies have found that bedaquiline has serious side effects due to high lipophilicity. Recently, the complete structure of ATP synthase was first reported in the Journal of Science. Objective: The study aimed to design, synthesise and carry out biological evaluation of antituberculosis agents based on the structure of bedaquiline. Methods: The mode of action of bedaquiline and ATP synthase was determined by molecular docking, and a series of low lipophilic bedaquiline derivatives were synthesized. The inhibitory activities of bedaquiline derivatives towards Mycobacterium phlei 1180 and Mycobacterium tuberculosis H37Rv were evaluated in vitro. A docking study was carried out to elucidate the structureactivity relationship of the obtained compounds. The predicted ADMET properties of the synthesized compounds were also analyzed. Results: The compounds 5c3, 6a1, and 6d3 showed good inhibitory activities (MIC=15.62 ug.mL-1). At the same time, the compounds 5c3, 6a1, and 6d3 also showed good drug-like properties through molecular docking and ADMET properties prediction. Conclusion: The results of in vitro anti-tuberculosis activity assays, docking studies and ADMET predictions indicate that the synthesized compounds have potential antifungal activity, with compounds 6a1 being further optimized and developed as lead compounds.

Synthesis, Spectroscopic Characterization and Biological Evaluation of 1-(4'-Hydroxybenzamido)-Imine-1,2,3,4-Tetrahydrocarbazole Derivatives

2017 ◽  
Vol 6 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Munusamy Saravanabhavan ◽  
Ambason Franklin Ebenazer ◽  
Venkatesan Murugesan ◽  
Marimuthu Sekar
Keyword(s):  
Antioxidant Properties ◽  
Spectroscopic Characterization ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Assay Method ◽  
Oh Radicals ◽  
Synthetic Approach ◽  
Anticancer Activities

A facile synthetic approach towards 1-(4'-hydroxybenzamido)-imine-1,2,3,4-tetrahydrocarbazole derivatives 3a–g was reported via reaction of 1-oxo-1,2,3,4-tetrahydrocarbazoles 1a–g, with p-hydroxybenzhydrazide in ethanol in the presence of sufficient amount of acetic acid. The structure of all the compounds was confirmed by spectroscopic studies. The antioxidant properties of all the derivatives have also been checked against DPPH and OH radicals. Further, in vitro anticancer activities of all the synthesized compounds were investigated by MTT assay method. All the prepared analogues exhibited considerable anticancer properties especially, 3e and 3f which reveled the best anticancer activity among all the test compounds. Additionally, we carried out molecular docking studies using the protein kinase CK2 inhibitors. In all the biological assays, halogen substituted carbazole derivatives showed enhanced activities than the other derivatives.

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