Design, Synthesis and Evaluation of Aryloxybenzylidene Hydrazinyl-Benzoxazoles/Benzothiazoles Analogs as Antimycobacterial Agents

2020 ◽  
Vol 5 (3) ◽  
pp. 185-191
Author(s):  
G. Aruna ◽  
Ravindra Kulkarni ◽  
Baswaraj Machaa ◽  
Malathi Jojula ◽  
Shravan Gunda ◽  
...  
Keyword(s):  
Spectral Data ◽  
Condensation Reaction ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Molecular Hybridization ◽  
Design Synthesis ◽  
Antitubercular Drugs ◽  
Pantothenate Synthetase ◽  
Antimycobacterial Agents ◽  
Mic Value

Substituted 2-(2-(4-aryloxybenzylidene)hydrazinyl)benzothiazole/benzoxazoles series were designed through molecular hybridization and synthesized in condensation reaction of hydrazinylbenzothiazole/ benzoxazole with substituted aryloxy benzaldehydes. All the synthesized compounds were assigned structure based on spectral data and were evaluated for antimycobacterial activity. Among both benzothiazole and benzoxazole derivatives, the compounds 8f and 9e were found to show most potent antitubercular activity with MIC value of 0.89 and 0.92 μM which are on a par with those of standard antitubercular drugs. In order to know the binding interactions of all the compounds were docked within the mycobacterial pantothenate synthetase, which showed interactions with Asp88, Arg200, Ser196, Asn199, Met 195 and Lys 160 of pantothenate synthetase.

scholarly journals Design, synthesis, characterization and antitubercular activity of some nov-el 2, 4-disubstituted thiazole derivatives

2019 ◽  
Vol 10 (2) ◽  
pp. 1504-1509
Author(s):  
Gobala Krishnan P ◽  
Gnanaprakash K ◽  
Chandrasekhar KB
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Condensation Reaction ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Alamar Blue ◽  
Thiazole Derivatives ◽  
Design Synthesis ◽  
Literature Reviews ◽  
Mic Value

Literature reviews reveal that thiazole and pyrazine carboxamide derivatives exhibit anticonvulsant, antimicrobial, anticancer and anti-tubercular activities due to the presence of –S-C=N- and-CO–NH- moiety. A series of thiazolyl pyrazine carboxamide derivatives (5a-j) were synthesized by condensation reaction between 2-amino, 4-substituted phenyl 2-amino thiazole and pyrazine 2-carboxylic acid. These synthesized thiazole derivatives (5a-j) were evaluated for their inhibitory activity against Mycobacterium tuberculosis (Mtb), H37Rv using microplate Alamar Blue assay (MABA). The compound, 5c and 5h showed high anti-mycobacterial activity with MIC value of 6.25 µg/ml, and the compound 5g also exhibited anti-mycobacterial activity with MIC value of 12.50 µg/ml. Molecular docking studies of these synthesized molecules with b-Ketoacyl-ACP Synthase (KasA) protein of Mycobacterium tuberculosis (Mtb) have been carried out to understand the mechanism of anti-mycobacterial action.

Design, Synthesis and Biological Evaluation of Carbazole Derivatives as Antitubercular and Antibacterial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 83-97
Author(s):  
Satheeshkumar Sellamuthu ◽  
Mohammad F. Bhat ◽  
Ashok Kumar ◽  
Gopal Nath ◽  
Sushil K. Singh
Keyword(s):  
Structural Similarity ◽  
Antitubercular Activity ◽  
Vero Cells ◽  
Antibacterial Activities ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Antitubercular Drugs ◽  
Carbazole Derivatives ◽  
Antipsychotic Activity ◽  
Bbb Permeability

Background:The neuroleptic chlorpromazine has been reported for antitubercular activity but the associated antipsychotic activity restricted its clinical presentation.Objectives:Novel derivatives of carbazole having structural similarity with chlorpromazine were designed, in an attempt to reduce the associated side effects, while retaining the antitubercular activity.Materials and Methods:The designed molecules were synthesized and screened for antitubercular and antibacterial activities. The blood-brain barrier (BBB) permeability and mammalian cell (VERO) cytotoxicity (CC50) were examined to determine the safety of compounds.Results:Among the developed compounds, 14c, 15c, 16c and 17c were found to be promising against Mtb H37Rv at MIC of 1.56 µg/ml. They were also effective against S. aureus and E. coli at MIC of 0.98 and 7.81 µg/ml, respectively. The BBB permeability of the compounds was found to be less than chlorpromazine. Therefore, the developed compounds are expected to have diminished antipsychotic effect. The compounds were further marked safe against mammalian VERO cells at CC50 > 90 µg/ml.Conclusion:The profound antitubercular activity with a concomitant reduction in BBB permeability of carbazole derivatives can pave new vista in the discovery of antitubercular drugs.

Synthesis and antimycobacterial activity of 3-(Arylaminomethyl)-5-(Pyridin-4-yl)-1,3,4-oxadiazole-(3H)-thi-2-one Derivatives against Mycobacterium tuberculosis H37rv Strain

2020 ◽  
Vol 16 ◽  
Author(s):  
Mohammad Asif ◽  
Mohd Imran
Keyword(s):  
Antimycobacterial Activity ◽  
Mannich Bases ◽  
Tuberculosis H37rv ◽  
Biologically Active ◽  
Mass Spectral ◽  
Mycobacterium Tuberculosis H37rv ◽  
H37rv Strain ◽  
Antimycobacterial Agents ◽  
Oxadiazole Derivatives ◽  
Mic Value

Background: Oxadiazole derivatives are the biologically active hetrocyclic compounds. So we synthesized a series of Mannich bases, 3-(arylaminomethyl)-5-(pyridin-4-yl)- 1,3,4-oxadiazole-(3H)-thi-2-one derivatives (3a-3g) were synthesized from Isoniazid [INH (1)], a first line antimycobacterial drug and these compounds were evaluated as antimycobacterial agents. Methods: The INH was reacted with potassium hydroxide and carbon disulfide to gives 5- (pyridin-4-yl)-1,3,4-oxadiazole-2(3H)-thione (2), followed by reacting of compound 2 with appropriate aromatic amines in the presence of formaldehyde to obtained desired compounds (3a-3g). The structures of these compounds have been established by IR, 1H-NMR and Mass spectral and elemental analysis. These synthesized compounds (3a-3g) were evaluated for their antimycobacterial activity against M. tuberculosis H37Rv strain. Results: All the synthesized compounds (3a-3g) were exhibited antimycobacterial activity and compared to reference drugs Streptomycin (MIC value of 6.25μg/mL), INH (MIC value of 3.125μg/mL) and pyrizinamide (MIC value of 3.125μg/mL). Compounds 3c and 3e were exhibited most promising antimycobacterial activity. Conclusion: All the title compounds were synthesized, characterized and exhibited promising antimycobacterial activity against M. tuberculosis H37Rv strain.

Benzoylthioureas: Design, Synthesis and Antimycobacterial Evaluation

2020 ◽  
Vol 16 (1) ◽  
pp. 93-103
Author(s):  
Tiago O. Brito ◽  
Lethícia O. Abreu ◽  
Karen M. Gomes ◽  
Maria C.S. Lourenço ◽  
Patricia M.L. Pereira ◽  
...  
Keyword(s):  
Benzene Ring ◽  
Biological Activities ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
New Drugs ◽  
Design Synthesis ◽  
Thiourea Derivatives ◽  
Structural Modifications ◽  
General Series ◽  
Wide Range

Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed. In this context, thiourea derivatives have a wide range of biological activities, including anti-TB. This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea as a pharmacophore group. Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of fifty-nine benzoylthioureas derivatives. Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship study of this series of compounds has been performed. Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1 and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the para-position in benzene ring plays an important role in the antitubercular activity of Series A. These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2 and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general, Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles. Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the first line anti-TB drug ethambutol and 0.65 times less active than isoxyl.

scholarly journals SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF PIPERIDINE AND MORPHOLINE 1, 8 NAPHTHYRIDINE ANALOGUES

2016 ◽  
Vol 8 (12) ◽  
pp. 252 ◽  
Author(s):  
Muwaffag Badawneh ◽  
Jalal Aljamal
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inhibitory Concentration ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Significant Activity ◽  
Reference Drug ◽  
Novel Drugs ◽  
Elemental Analyses ◽  
Antimycobacterial Agents

<p><strong>Objective: </strong>The search for new, potentially useful antimycobacterial agents. In continuation with our previous screening for the discovery of novel drugs for tuberculosis, a new series of 1,8-naphthyridines derivatives were synthesized and evaluated <em>in vitro </em>for antimycobacterial activity against <em>Mycobacterium tuberculosis </em>H37Rv.</p><p><strong>Methods: </strong>Several 4-morpholinomethyl-1.8-naphthyridine derivatives have been synthesized in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimycobacterial activity. The growth was monitored radiometrically in 7H12 broth with the BACTEC 460 TB system. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated ≥ 90% growth inhibition in the primary screening.</p><p><strong>Results: </strong>The obtained data suggested that all compounds showed significant activity against <em>Mycobacterium tuberculosis </em>H37Rv<em> </em>compared to the standard reference drug. Analogues (6-11) having heterocyclic groups in position 7 were the most potent of those we tested.</p><p><strong>Conclusion: </strong>These findings clearly identify the 1,8-naphthyridine analogue (10) with a 6-amino-2-(4'-methoxy benzylamine-4-morpholinomethyl-7-morpholino-substituent as promising anti-tubercular agents possessing significant activity against <em>Mycobacterium tuberculosis </em>H37Rv</p>

Ring Functionalization and Molecular Hybridization of Quinolinyl Pyrazole: Design, Synthesis and Antimycobacterial Activity

2017 ◽  
Vol 2 (22) ◽  
pp. 6529-6534
Author(s):  
Venkatesham Rachakonda ◽  
Sudha Sravanti Kotapalli ◽  
Ramesh Ummanni ◽  
Manjula Alla
Keyword(s):  
Antimycobacterial Activity ◽  
Molecular Hybridization ◽  
Design Synthesis

scholarly journals Design, Synthesis and Study of Antibacterial and Antitubercular Activity of Quinoline Hydrazone Hybrids

2020 ◽  
Vol 26 (1) ◽  
pp. 137-147
Author(s):  
Shruthi T G ◽  
Sangeetha Subramanian ◽  
Sumesh Eswaran
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bacterial Resistance ◽  
Biological Activities ◽  
Antitubercular Activity ◽  
Bacterial Strains ◽  
Acinetobacter Baumanii ◽  
Design Synthesis ◽  
Mic Value

AbstractEmerging bacterial resistance is causing widespread problems for the treatment of various infections. Therefore, the search for antimicrobials is a never-ending task. Hydrazones and quinolines possess a wide variety of biological activities. Herewith, eleven quinoline hydrazone derivatives have been designed, synthesized, characterized and evaluated for their antibacterial activity and antitubercular potential against Mtb WT H37Rv. Compounds QH-02, QH-04 and QH-05 were found to be promising compounds with an MIC value of 4 μg/mL against Mtb WT H37Rv. Compounds QH-02, QH-04, QH-05, and QH-11 were also found to be active against bacterial strains including Acinetobacter baumanii, Escherichia coli and Staphylococcus aureus. Further, we have carried out experiments to confirm the cytotoxicity of the active compounds and found them to be non-toxic.

Design, synthesis and antimycobacterial activity of cinnamide derivatives: A molecular hybridization approach

2011 ◽  
Vol 21 (7) ◽  
pp. 1997-1999 ◽  
Author(s):  
Manoj D. Kakwani ◽  
Prashant Suryavanshi ◽  
Muktikant Ray ◽  
M.G.R. Rajan ◽  
Sharmila Majee ◽  
...  
Keyword(s):  
Antimycobacterial Activity ◽  
Molecular Hybridization ◽  
Design Synthesis

A Comparative Study of 1D Descriptors Supported CoMFA and CoMSIA QSAR Models to Gain Novel Insights into 1,2,4-Triazoles Acting As Antitubercular Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Rajdeep Ray ◽  
Gautham Shenoy ◽  
N V Ganesh Kumar Tummalapalli
Keyword(s):  
External Validation ◽  
Antitubercular Activity ◽  
New Drugs ◽  
Rational Approach ◽  
Antitubercular Drugs ◽  
Comfa Model ◽  
Qsar Models ◽  
Structural Insights ◽  
The Way

: Tuberculosis is one of the leading cause for deaths due to infectious disease worldwide. There is an urgent need for developing new drugs due to the rising incidents of drug resistance. Triazoles have previously been reported to show antitubercular activity. Various computational tools pave the way for a rational approach in understanding the structural importance of these compounds in inhibiting Mycobacterium tuberculosis growth. The aim of this study is to develop and compare two different QSAR models based on a set of previously reported molecules and use the best one for gaining structural insights in to the Triazole molecules. In the current study, two separate models were generated with CoMFA and CoMSIA descriptors respectively based on a dataset of triazole molecules showing antitubercular activity. Several one dimensional (1D) descriptors were added to each of the models and the validation results and the contour data generated from them were compared. The best model was studied to give a detailed understanding of the triazole molecules and their role in the antitubercular activity.The r2, q2, predicted r2 and SEP (Standard error of prediction) for the CoMFA model were 0.866, 0.573, 0.119 and 0.736 respectively and for the CoMSIA model the r2, q2, predicted r2 and SEP were calculated to be 0.998, 0.634, 0.013 and 0.869 respectively. Although both the QSAR models produced acceptable internal and external validation scores but the CoMSIA results were significantly better. The CoMSIA contours also provided a better match than CoMFA with most of the features of the active compound 30b. Hence, the CoMSIA model was chosen and its contours were explored for gaining structural insights on the triazole molecules. The CoMSIA contours helped us to understand the role of several atoms and groups of the triazole molecules in their biological activity. The possibilities for substitution in the triazole compounds that would enhance the activity were also analysed. Thus, this study paves the way for designing new antitubercular drugs in future.

scholarly journals ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3667
Author(s):  
Mashooq A. Bhat ◽  
Ahmed M. Naglah ◽  
Siddique Akber Ansari ◽  
Hanaa M. Al-Tuwajiria ◽  
Abdullah Al-Dhfyan
Keyword(s):  
Reaction Times ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Environmentally Benign ◽  
Reaction Yield ◽  
Benign Synthesis ◽  
Xanthene Derivatives ◽  
Wide Range ◽  
Major Application

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5−15.10 µg/mL and 0.26–14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

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