scholarly journals Synthesis, Characterization, and Biological Evaluation of Novel 7-Oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic Acid Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1307
Author(s):  
Dong Cai ◽  
Tai Li ◽  
Qian Xie ◽  
Xiaofei Yu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Intramolecular Cyclization ◽  
Antibacterial Properties ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Trna Synthetase ◽  
Ethyl Esters ◽  
X Ray Diffraction ◽  
Step Procedure

A series of novel 7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid derivatives was synthesized in good yields by a multi-step procedure that included the generation of the S-alkylated derivatives from 6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones with ethyl 2-chloroacetoacetate, intramolecular cyclization with microwave irradiation, hydrolysis and amidation. All of the target compounds were fully characterized through 1H-NMR, 13C-NMR and HRMS spectra. The intramolecular cyclization occurred regioselectively at the N2-position of 1,2,4-triazine ring, which was confirmed by compound 3e using single-crystal X-ray diffraction analysis. The antibacterial and antitubercular activities of the target compounds were evaluated. Compared with Ciprofloxacin and Rifampicin, compounds 5d, 5f and 5g containing the terminal amide fragment exhibited broad spectrum antibacterial activity, and carboxylic acid derivatives or its corresponding ethyl esters had less effect on antibacterial properties. The most potent compound 5f also displayed excellent in vitro antitubercular activity against Mycobacterium smegmatis (minimum inhibitory concentration (MIC) = 50 μg/mL) and better growth inhibition activity of leucyl-tRNA synthetase (78.24 ± 4.05% at 15 μg/mL).

Synthesis and Biological Evaluation of 3,4-Dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic Acid Derivatives as Antitubercular Agents

2020 ◽  
Vol 5 (2) ◽  
pp. 138-148
Author(s):  
Macchindra S. Tambe ◽  
Sonali Gadhe ◽  
Amit Choudhari ◽  
Dhiman Sarkar ◽  
Jaiprakash N. Sangshetti ◽  
...  
Keyword(s):  
Free Energy ◽  
Carboxylic Acid ◽  
Binding Site ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Antibacterial Screening ◽  
Free Energy Of Binding

A series of side chain modified structurally diverse 3,4-dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic acid derivatives were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral study. All the newly synthesized compounds were examined for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra. The synthesized compounds exhibited minimum inhibitory concentration (IC50) ranging from 5.98 to >30 (μg/mL) against MtbH37Ra. Among the screened compounds, compounds 5a, 5c, 5d, 5f, 5g, 5h, 5I, 5j exhibited IC50 as 10.42, 11.81, 18.79, 5.98, 19.21, 24.81 and 14.81 μg/mL, respectively. The antibacterial screening study of these compounds was conducted against four different bacteria to asses there selectivity towards MTB. The antibacterial screening of all the synthesized compounds was conducted against four bacterial strains (Gram-negative strains: E.coli and S.aureus; Gram-positive strains: P. aeruginosa and B.subtilis. The compounds 5a, 5b, 5c, 5e and 5j showed higher antibacterial activity up to 7-25 μg/mL. Furthermore, molecular docking studies revealed the binding modes of the compounds in the binding site of the good agreement with the in vitro antitubercular screening. The compounds 5a, 5c and 5f with free energy of binding lower than -9.0 Kcal/mol binds more favourably at the binding site of panC as compared to other compounds. Specifically, the compound 5f with free energy of binding -9.6 Kcal/mol is indeed found more active in docking study as well as in the in vitro antitubercular screening. These findings open the possibility for potential lead for antituberculosis chemotherapy.

Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

2020 ◽  
Vol 17 (3) ◽  
pp. 365-375
Author(s):  
Vasyl Kovalishyn ◽  
Diana Hodyna ◽  
Vitaliy O. Sinenko ◽  
Volodymyr Blagodatny ◽  
Ivan Semenyuta ◽  
...  
Keyword(s):  
Machine Learning ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Predictive Ability ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Starting Point ◽  
Binary Classifiers ◽  
Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

scholarly journals Synthesis, Characterization, Antibacterial Properties, and In Vitro Studies of Selenium and Strontium Co-Substituted Hydroxyapatite

2021 ◽  
Vol 22 (8) ◽  
pp. 4246
Author(s):  
Muhammad Maqbool ◽  
Qaisar Nawaz ◽  
Muhammad Atiq Ur Atiq Ur Rehman ◽  
Mark Cresswell ◽  
Phil Jackson ◽  
...  
Keyword(s):  
Negative Impact ◽  
Antibacterial Properties ◽  
Biological Properties ◽  
Ion Concentration ◽  
Charge Composition ◽  
Bacterial Strains ◽  
X Ray Diffraction ◽  
Molar Ratios ◽  
Human Osteosarcoma Cells

In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32−) in HA, strontium (Sr2+) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell–material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications.

scholarly journals Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Saundane Anand Raghunath ◽  
Kirankumar Nandibeoor Mathada
Keyword(s):  
Radical Scavenging ◽  
Antitubercular Activity ◽  
Antimicrobial Activities ◽  
Biological Evaluation ◽  
Secondary Amines ◽  
Anticancer Activities ◽  
One Pot ◽  
Antioxidant Power ◽  
Mic Value

An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3-carboxaldehydes (2), and secondary amines (3) has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene-ols (4) derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r) are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r), the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland) cell lines.

scholarly journals Synthesis of Novel Sulfamethaoxazole 4-Thiazolidinone Hybrids and Their Biological Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3570 ◽  
Author(s):  
Mashooq A. Bhat ◽  
Mohamed A. Al-Omar ◽  
Ahmed M. Naglah ◽  
Azmat Ali Khan
Keyword(s):  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Biological Evaluation ◽  
Oral Drug ◽  
Drug Candidates ◽  
Cyclocondensation Reaction ◽  
Aryl Aldehyde ◽  
Hct 116 ◽  
Mcf 7

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (7a–l) by using a cyclocondensation reaction between 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a–l), and mercapto acetic acid (6) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra (MTB) strains. The compounds 7d, 7g, 7i, 7k, and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC90 values in the range of 0.058–0.22 and 0.43–5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.

scholarly journals Novel Nonsymmetrically p-Benzyl-Substituted (Benz)imidazole N-Heterocyclic Carbene-Silver(I) Acetate Complexes: Synthesis and Biological Evaluation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Frauke Hackenberg ◽  
Anthony Deally ◽  
Grainne Lally ◽  
Sina Malenke ◽  
Helge Müller-Bunz ◽  
...  
Keyword(s):  
Cancer Cell Line ◽  
Benzyl Bromide ◽  
Biological Evaluation ◽  
Diffusion Method ◽  
X Ray Diffraction ◽  
Gram Positive Bacteria ◽  
Acetate Complex ◽  
Renal Cancer Cell ◽  
Synthesis And Biological Evaluation

Nonsymmetrically substituted N-heterocyclic carbene (NHC) precursors 1a–d and 3a–d were synthesised by first reacting 1H-(benz)imidazole with p-cyanobenzyl bromide to give 4-(1H-imidazole-1-ylmethyl)benzonitrile (1) and 4-(1H-benzimidazole-1-ylmethyl)benzonitrile (3) and afterwards introducing benzyl bromide, 1-(bromomethyl)-4-methylbenzene, 1-(bromomethyl)-4-methoxybenzene, and methyl 4-(bromomethyl)benzoate. The NHC-silver(I) acetate complexes (1-benzyl-3-(4-cyanobenzyl)-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate (2a), (1-(4-cyanobenzyl)-3-(4-methylbenzyl)-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate (2b), (1-(4-cyanobenzyl)-3-[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate (2c), (1-benzyl-3-(4-cyanobenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate (4a), (1-(4-cyanobenzyl)-3-(4-methylbenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate (4b), (1-(4-cyanobenzyl)-3-(4-methoxybenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate (4c), and (1-(4-cyanobenzyl)-3-[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate (4d) were yielded by reacting these NHC precursors with silver(I) acetate. The silver(I) acetate complex 4b was characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial studies against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli, using the Kirby-Bauer disc diffusion method, were carried out on the seven NHC-silver(I) acetate complexes 2a–c and 4a–d. Also the IC50 values of these seven complexes were determined by an MTT-based assay against the human renal cancer cell line Caki-1. The complexes 2a–c and 4a–c revealed the following IC50 values, respectively, 25 (±1), 15 (±2), 5.4 (±0.8), 16 (±2), 7.1 (±1), 20 (±4), and 14 (±1) μM.

scholarly journals Design, Synthesis, and In Vitro Evaluation of Benzofuro[3,2-c]Quinoline Derivatives as Potential Antileukemia Agents

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 203 ◽  
Author(s):  
Ying Lin ◽  
Dong Xing ◽  
Wen-Biao Wu ◽  
Gao-Ya Xu ◽  
Li-Fang Yu ◽  
...  
Keyword(s):  
Intramolecular Cyclization ◽  
Biological Evaluation ◽  
Quinoline Derivatives ◽  
Reaction Conditions ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
Metal Free ◽  
Sequential Transformation ◽  
High Yields

Herein, we design and synthesize an array of benzofuro[3,2-c]quinolines starting from 3-(2-methoxyphenyl)quinolin-4(1H)ones via a sequential chlorination/demethylation, intramolecular cyclization pathway. This sequential transformation was efficient, conducted under metal-free and mild reaction conditions, and yielded corresponding benzofuro[3,2-c]quinolines in high yields. In vitro biological evaluation indicated that such type of compounds showed excellent antileukemia activity and selectivity, and therefore may offer a promising hit compound for developing antileukemia compounds.

Synthesis and biological evaluation of newer 1,3,4-oxadiazoles incorporated with benzothiazepine and benzodiazepine moieties

2017 ◽  
Vol 72 (3-4) ◽  
pp. 133-146 ◽  
Author(s):  
Patel Navin ◽  
Patel Sarvil ◽  
Purohit Amit ◽  
Patel Divyesh ◽  
Rajani Dhansukh ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Giardia Lamblia ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Leishmania Mexicana ◽  
Aspergillus Clavatus ◽  
Biological Screening ◽  
Synthesis And Biological Evaluation

Abstract A series of thiazepines and diazepines having 1,3,4-oxadiazole moiety were synthesized, and they were analyzed for their in vitro antimicrobial activity against several bacteria (Staphylococcus aureus, Staphylococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, and Aspergillus Clavatus) and protozoa (Entamoeba histolytica, Giardia lamblia, Trypanosoma cruzi and Leishmania mexicana). Few of the selected compounds were tested for their antitubercular activity. However, it was noticed that the potency of final analogs against each strain placed reliance on the type of substituent present on aryl ring of oxadiazole as well as presence of thiophene, pyridine, and furan at benzothiazepines and benzodiazepines. The biological screening identified that some of the compounds were found to possess good antimicrobial and antitubercular (62.5–100 μg/mL of MIC) activity.

scholarly journals Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5320
Author(s):  
Shouting Wu ◽  
Xi Liang ◽  
Fang Luo ◽  
Hua Liu ◽  
Lingyi Shen ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Condensation Reaction ◽  
Acid Hydrazide ◽  
13C Nmr Spectroscopy ◽  
X Ray Diffraction ◽  
1H And 13C Nmr ◽  
X Ray ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Thiazolyl Blue Tetrazolium

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

Sign in / Sign up

Export Citation Format

Share Document