Synthesis of Substituted -N-(5-((7-Methyl-2-Oxo-2H-Chromen-4-yl)-Methyl)-1,3,4-Thiadiazol-2-yl)-Benzamide Derivatives Using TBTU As Coupling Agent And Their Evaluation For Anti Tubercular Activity

2021 ◽  
Vol 18 ◽  
Author(s):  
Monika Kakadiya ◽  
Yunus Pasha ◽  
Malleshappa Noolvi ◽  
Ashish Patel
Keyword(s):  
Antitubercular Activity ◽  
Side Chain ◽  
Antitubercular Agents ◽  
Facile Synthesis ◽  
Aromatic Side Chain ◽  
Reaction Conditions ◽  
Coupling Reagent ◽  
H37rv Strain ◽  
Benzamide Derivatives

: Tuberculosis remains a highly infectious disease across the world. In the identification of new antitubercular agents, coumarin clubbed thiadiazole amides have been synthesized and evaluated for in vitro antitubercular activity. Due to the growing concern about chemicals and their impact on the environment, greener and faster reaction conditions needed to be incorporated. Therefore, we used TBTU as a coupling reagent for efficient and facile synthesis of substituted-N-(5-((7-methyl-2-oxo-2H-chromes-4-yl)-methyl)-1,3, 4 - thiadiazol-2-yl)-benzamide 4a-j with good yields up to 95% in mild reaction condition. All the synthesized compounds were evaluated in vitro for antitubercular activity against the H37Rv strain of M.Tuberculosis. Compounds 4c, 4f, and 4j were found active at 25 µg/mL against M. tb H37Rv. Electron withdrawing substituents present on aromatic side-chain showed promising anti-tubercular activity.

Concise and Facile Synthesis of Novel Pyrano[2,3-d]pyrimidine-7- one/thione Derivatives as In Vitro Antimicrobial and Antitubercular Agents

2011 ◽  
Vol 8 (8) ◽  
pp. 750-757 ◽  
Author(s):  
Prashant T. Mistry ◽  
Nimesh R. Kamdar ◽  
Dhaval D. Haveliwala ◽  
Saurabh K. Patel
Keyword(s):  
Antitubercular Agents ◽  
Facile Synthesis

Synthesis, In silico and Biological Studies of Thiazolyl-2h-chromen-2-one Derivatives as Potent Antitubercular Agents

2020 ◽  
Vol 16 (5) ◽  
pp. 511-522 ◽  
Author(s):  
Bhagwat S. Jadhav ◽  
Ramesh S. Yamgar ◽  
Rajesh S. Kenny ◽  
Suraj N. Mali ◽  
Hemchandra K. Chaudhari ◽  
...  
Keyword(s):  
Schiff Base ◽  
In Silico ◽  
Antitubercular Activity ◽  
Inhibition Mechanism ◽  
Mycobacterium Tuberculosis H37rv ◽  
Schiff Base Derivatives ◽  
Biological Studies ◽  
H37rv Strain ◽  
Modeling Software

Background: A series of new six thiazolyl-2-amine-based Schiff base derivatives (4a-4f) were synthesized by a sequential multistep reaction starting with Salicylaldehyde. Methods: All the Schiff base derivatives were screened in-vitro for their antibacterial activity against Mycobacterium tuberculosis (H37RV strain) ATCC No-27294. The synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and Mass spectrometry. Results: Among the compounds tested, 4c and 4f derivatives exhibited potent antitubercular activity against M. tuberculosis at MIC 6.25 μg/mL. Conclusion: We extended our study to explore the inhibition mechanism by conducting molecular docking analysis by using Schrodinger’s molecular modeling software. All the newly synthesized compounds were found to be in-silico AMES test non-toxic and non-carcinogens. The good Qikprop’s Absorption, Distribution, Metabolism and Excretion (ADMET) would definitely help the researchers in order to make more potent Anti-TB agents.

Novel Benzylidenehydrazide-1,2,3-Triazole Conjugates as Antitubercular Agents: Synthesis and Molecular Docking

2019 ◽  
Vol 19 (14) ◽  
pp. 1178-1194 ◽  
Author(s):  
Mubarak H. Shaikh ◽  
Dnyaneshwar D. Subhedar ◽  
Laxman Nawale ◽  
Dhiman Sarkar ◽  
Firoz A. Kalam Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Antitubercular Agents ◽  
Molecular Docking Study ◽  
Activity Data ◽  
Structure Activity ◽  
Starting Point ◽  
Adme Properties

Background & Objectives:Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values.Methods:Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG.Results:The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions.Conclusion:Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.

scholarly journals Synthesis and evaluation of β-hydroxytriazoles and related compounds as antitubercular agents

2015 ◽  
Vol 3 (1) ◽  
pp. 82-96 ◽  
Author(s):  
Christophe Menendez ◽  
Giorgia Mori ◽  
Mathilde Maillot ◽  
Isabelle Fabing ◽  
Chantal Carayon ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antitubercular Activity ◽  
Propargyl Bromide ◽  
Antitubercular Agents ◽  
Oxidation Reactions ◽  
Mycobacterium Tuberculosis H37rv ◽  
Barbier Reaction ◽  
New Compounds ◽  
Related Compounds

A new series of β-hydroxytriazoles were synthesized and evaluated as Mycobacterium tuberculosis inhibitors. Our strategy implied the synthesis of alkyne precursors through a Barbier reaction between benzaldehydes and propargyl bromide followed by click chemistry to afford substituted β-hydroxyl benzyltriazoles. These compounds are also key intermediates either for oxidation reactions leading to α,β-diketotriazoles or for elimination reactions affording styryl triazoles. Evaluation of all new compounds for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv resulted in compounds with MIC up to 7 μM.

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 Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones

2021 ◽  
Author(s):  
Balungile Madikizela ◽  
Tamira Eckhardt ◽  
Richard Goddard ◽  
Adrian Richter ◽  
Anika Lins ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Antitubercular Activity ◽  
In Vitro Testing ◽  
Antitubercular Agents ◽  
Cell Wall Synthesis ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Class ◽  
Mycobacterium Aurum

Abstract8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. Synthesis, structural characterization and in vitro testing against Mycobacterium aurum DSM 43999 and M. tuberculosis H37Rv of halogenated 2-(4-ethoxycarbonylpiperazin-1-yl)-1,3-benzothiazin-4-ones lacking a nitro group are reported. X-ray crystallography reveals that the structure of the BTZ scaffold can significantly deviate from planarity. In contrast to recent reports, the results of the present study indicate that further investigation of halogenated non-nitro BTZs for antitubercular activity is less than a promising approach.

In Silico (3D-QSAR) Designed, Study, Synthesis and Anti-tubercular Evaluation of Pyrazolo-Pyrimidine Derivatives

2020 ◽  
Vol 18 (2) ◽  
pp. 135-143
Author(s):  
Pratiksha Chhatbar ◽  
Kaushik Pambhar ◽  
Vijay Khedkar ◽  
Anamik Shah ◽  
Ranjan Khunt
Keyword(s):  
3D Qsar ◽  
Antitubercular Activity ◽  
Tuberculosis H37rv ◽  
Eukaryotic Cells ◽  
Antitubercular Agents ◽  
Pyrimidine Derivatives ◽  
Qsar Study ◽  
Chemical Structures ◽  
Microbial Study

Background: A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole-pyrimidine derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. Objective: The current research aimed to synthesize and evaluateed pyrazole-pyrimidine based antitubercular agents by an in vitro microbial study based on our previously reported 3D-QSAR. Methods: The designed molecules were synthesised via chalcone intermediate and cyclisation using guanidine and urea. The molecules were then characterized by various spectroscopic methods like IR, MASS, 1H-NMR, 13C-NMR and in vitro evaluation against M. tuberculosis H37Rv. They were further evaluated under anaerobic condition and their intracellular assay was studied. The compounds were further examined for cytotoxicity towards eukaryotic cells. Results: Compounds 3a, 3c and 3i were found to be the most effective against M. tuberculosis H37Rv, with IC50 of 16μM, 13μM and 15μM, respectively. Conclusion: The designed strategy, to enhance the antitubercular activity against M. tuberculosis H37Rv, was proved fruitful. On considering the overall data, the promising results would be useful to design the next target with improved efficacy and potency of compounds for further medicinal importance.

Synthesis and In vitro Antibacterial, Antitubercular Studies of Novel Fluoroquinolones Analogs Containing 4-substituted Sec Amine

2020 ◽  
Vol 15 (6) ◽  
pp. 656-664
Author(s):  
Ravi K. Akula ◽  
Shanthan R. Pamulaparthy ◽  
Pranay K. Koochana ◽  
Dharmarajan Sriram
Keyword(s):  
Antitubercular Activity ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Antitubercular Drugs ◽  
Mycobacterium Tuberculosis H37rv ◽  
H37rv Strain ◽  
In Vitro Antibacterial Activity ◽  
Comparable Activity

Background: Tuberculosis is a contagious, air borne disease and second leading cause of death among infectious diseases worldwide. Fluoroquinolones are well-known antibacterial agents and they were recommended as second-line of antitubercular drugs. Method: A series of novel fluoroquinolone analogs 6-24 was effectively synthesized. An attempt was made by tagging the substituted pyrazole on to fluoroquinolones for the first time at C-7 position. The newly synthesized compounds were characterized by FTIR, 1HNMR, ESI-MS, HR-MS and elemental analysis. The in vitro antibacterial activity of all the title compounds was investigated against various gram positive, gram negative bacterial organisms and in vitro antitubercular activity against Mycobacterium Tuberculosis H37Rv strain. Result: Most of the synthesized compounds showed comparable activity against the entire gram positive and gram negative bacterial organisms. Fluoroquinolone 16 showed enhanced activity against both type of bacterial strains and compound 11showed promising activity against MTB-H37Rv strain. Conclusion: Some of the novel fluoroquinolone analogs (11, 16) showed potent antibacterial, antitubercular activity.

Antitubercular Potential of Novel Isoxazole Encompassed 1, 2, 4-Triazoles: Design, Synthesis, Molecular Docking Study and Evaluation of Antitubercular Activity

2020 ◽  
Vol 18 ◽  
Author(s):  
Neenu Ganesh ◽  
Arun Kumar S ◽  
Manisha Singh ◽  
Venkaraddi Mangannavar Chandrashekar ◽  
Gurubasavaraj Veeranna Pujar
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Normal Cell ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Amino Acid Residues ◽  
Antitubercular Agents ◽  
Molecular Docking Study ◽  
Good Safety Profile

Background: Decaprenylphosphoryl-β-D-ribose epimerase (DprE1), a flavoprotein enzyme engaged in the biosynthesis of decaprenylphosphoryl-β-D-arabinofuranose (DPA), is the only contributor of arabinose residues which is fundamental for the mycobacterium cell wall constituents. DprE1 is an interesting target for antitubercular agent and has been exploring to develop potential chemical entities as antitubercular agents. Objective: The objective of study is the development of novel antitubercular agents targeting Mtb Decaprenylphosphoryl-βD-ribose epimerase (DprE1). Methods: A series of isoxazole encompassed 1, 2, 4-triazoles were designed based on the antitubercular potential of triazoles and structural features of DprE1 inhibitors. Designed 1, 2, 4-triazoles were synthesized and characterized by spectral studies. The in vitro anti-TB activity of the compounds was screened against Mycobacterium tuberculosis H37Rv strain.by Microplate Almar Blue Assay and in vitro cytotoxicity against normal cell lines by MTT assay. Molecular docking study was carried out on DprE1 enzyme to understand designed compounds interactions with amino acid residues at the active site. Results: Antitubercular activity data revels that eight compounds (6d, 6e,7d, 7e, 10d, 10e, 11d and 11e) have shown promising antitubercular activity with minimum inhibitory concentration at 1.6µg/mL. Cytotoxicity data of anti-TB active compounds demonstrate the good safety profile on normal cell lines. Conclusion: Eight compounds have shown promising antitubercular activity with good safety profile on normal cell lines. Molecular docking study ascertain that the synthesized compounds have shown non-covalent interactions with amino acid residues of DprE1 enzyme.

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