- Synthesis of coumarin-benzotriazole hybrids and evaluation of their anti-tubercular activity
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Background: Tuberculosis is one of the top ranked airborne infectious diseases caused by the bacillus Mycobacterium tuberculosis with high mortality rate from a single infectious agent. In the present article, we aimed to synthesize oxadiazole-coumarin-triazole based small molecules and evaluate for their possible anti-mycobacterial activity. Method: Herein, we describe the facile synthesis of 5-((1H-benzo[d][1, 2, 3]triazol-1-yl)methyl)-1, 3, 4- oxadiazole-2-thiol-tethered substituted 4-(bromomethyl)-7-methyl-2H-chromen-2-one derivatives and evaluated for their anti-mycobacterial activity against H37Rv strain of M. tuberculosis. We also evaluated the cytotoxic effect of new compounds on normal cells. Results: Among the 14 novel oxadiazole-coumarin-triazole derivatives, 4-((5-((1H-benzo[d][1, 2, 3]triazol-1- yl)methyl)-1, 3, 4-oxadiazol-2-ylthio)methyl)-6-methoxy-2H-chromen-2-one (5f) displayed good antimycobacterial activity towards M. tuberculosis with an MIC value of 15.5 μM. Pyrazinamide was used as reference drug. Our investigation also revealed that, 5f is not cytotoxic to normal cells. Conclusion: In summary, the findings suggested that novel 1, 3, 4-oxadiazole coumarin-triazole hybrids are promising antimycobacterial agents against M. tuberculosis.
- Ambekar, Sachin P.,Mohan, Chakrabhavi Dhananjaya,Shirahatti, Arunkumar,Kumar, Mahesh K.,Rangappa, Shobith,Mohan, Surender,Basappa,Kotresh, Obelannavar,Rangappa, Kanchugarakoppal S.
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- 1,3,4-Oxadiazole derivatives as potential antitumor agents: Discovery, optimization and biological activity valuation
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Recent studies have proved that focal adhesion kinase (FAK) is a new potential therapeutic target in cancer therapy. In this study, a virtual screening was conducted to discover potential candidates for FAK inhibitors. Based on the results, a series of novel oxadiazole derivatives (5a-5q) bearing the benzotriazole group were designed and synthesized for FAK inhibitory evaluation. Among the compounds, 5h, which has an ortho methoxy group on the benzene ring, exhibited the most potent inhibitory activity for cancer cell growth with an IC50 value of 11 μM and 0.250 μM against Hela cells and FAK, respectively. Further, the apoptosis assay indicated that compound 5h induced the apoptosis of HeLa cells, and docking simulation showed that 5h could bind to the FAK protein catalytic region. Taking these together, 5h could be a lead for discovering novel FAK inhibitors.
- Luo, Yin,Liu, Zhi-Jun,Chen, Guo,Shi, Jing,Li, Jing-Ran,Zhu, Hai-Liang
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- A “turn-on” small molecule fluorescent sensor for the determination of Al3+ion in real samples: theoretical calculations, and photophysical and electrochemical properties
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Aluminum, one of the most plentiful metal ions on Earth, demonstrates toxic effects after excessive accumulation in the environment and human bodies because it is a non-essential element for living organisms. Therefore, strict limits on Al3+intake by humans have been proposed by the EPA and WHO. In the current study, ultrasound sonication was used for the green synthesis of the naphthalene-based acetohydrazide derivative (3), and it was used as a fluorescent sensor in order to determine the levels of Al3+ions in real samples. Theoretical calculations were carried out and the photophysical and electrochemical properties of3were deeply investigatedviaDFT; steady-state fluorescence, UV-vis absorption, time-resolved fluorescence, and 3D-fluorescence spectroscopy; excitation-emission matrix (EEM) analysis; and CV and SWV measurements. The fluorescent sensor investigations demonstrated that3can sensitively and selectively detect Al3+ionsviaa “turn-on” fluorescence response, which is based on the inhibition of PET and ESIPT processes with a synergistic effect from CHEF. The optimal conditions with regards to the initial sensor concentration, pH, selectivity, and interaction time were determined for the detection of Al3+ions. The linear working range and detection limit for Al3+ions were calculated to be 1.00-20.00 μmol L?1and 0.34 μmol L?1, respectively. Method validation was examinedviathe analysis of a certified reference material (CRM-TMDW-500), and spike/recovery testing and spectrofluorimetric analysis of Al3+ions in drinking water, seawater, and urine samples were successfully carried out using3. Importantly,3-capped paper-based test strips were developed for the practical analysis and monitoring of Al3+ions in the field. According to the obtained results, the presented detection technique, which is based on a “turn-on” fluorescence response change of3, can be applied to the highly sensitive, facile, reliable, and fast determination of Al3+ions in real samples.
- ?enocak, Ahmet,Mermer, Arif,Tümay, Süreyya O?uz
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p. 18400 - 18411
(2021/10/19)
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- Synthesis and antimicrobial and antioxidant activities of hybrid molecules containing benzotriazole and 1,2,4-triazole
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Eleven novel 1,2,4-triazolylbenzotriazoles have been prepared using 1-(hydrazinylcarbonylmethyl)-1 H -benzotriazole (3) as a potent intermediate. Compound 3, however, was obtained from benzotriazole in two steps. All synthesized compounds were characteriz
- Chand, Mahesh,Kaushik, Reena,Chand Jain, Subhash
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p. 1663 - 1677
(2019/01/03)
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- Novel benzotriazole N-acylarylhydrazone hybrids: Design, synthesis, anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis and FAK inhibition
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A series of novel benzotriazole N-acylarylhydrazone hybrids was synthesized according fragment-based design strategy. All the synthesized compounds were evaluated for their anticancer activity against 60 human tumor cell lines by NCI (USA). Five compounds: 3d, 3e, 3f, 3o and 3q exhibited significant to potent anticancer activity at low concentrations. Compound 3q showed the most prominent broad-spectrum anticancer activity against 34 tumor cell lines, with mean growth inhibition percent of 45.80%. It exerted the highest potency against colon HT-29 cell line, with cell growth inhibition 86.86%. All leukemia cell lines were highly sensitive to compound 3q. Additionally, compound 3q demonstrated lethal activity to MDA-MB-435 belonging melanoma. Compound 3e exhibited the highest anticancer activity against leukemic CCRF-CEM and HL-60(TB) cell lines, with cell growth inhibition 86.69% and 86.42%, respectively. Moreover, it exerted marked potency against ovarian OVCAR-3 cancer cell line, with cell growth inhibition 78.24%. Four compounds: 3d, 3e, 3f and 3q were further studied through determination of IC50 values against the most sensitive cancer cell lines. The four compounds exhibited highly potent anticancer activity against ovarian cancer OVCAR-3 and leukemia HL-60 (TB) cell lines, with IC50 values in nano-molar range between 25 and 130 nM. They showed 18–2.3 folds more potent anticancer activity than doxorubicin. The most prominent compound was 3e, (IC50 values 29 and 25 nM against OVCAR-3 and HL-60 (TB) cell lines, respectively), representing 10 and 18 folds more potency than doxorubicin. The anti-proliferative activity of these four compounds appeared to correlate well with their ability to inhibit FAK at nano-molar range between 44.6 and 80.75 nM. Compound 3e was a potent, inhibitor of FAK and Pyk2 activity with IC50 values of 44.6 and 70.19 nM, respectively. It was 1.6 fold less potent for Pyk2 than FAK. Additionally, it displayed inhibition in cell based assay measuring phosphorylated-FAK (IC50 = 32.72 nM). Inhibition of FAK enzyme led to a significant increase in the level of active caspase-3, compared to control (11.35 folds), accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining in addition to cell cycle arrest at G2/M phase indicating that cell death proceeded through an apoptotic mechanism.
- Kassab, Asmaa E.,Hassan, Rasha A.
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p. 531 - 544
(2018/07/25)
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- Stereoselective synthesis and spectral studies of some benzotriazolylacetyl hydrazones of 3–alkyl–2,6–diarylpiperidin–4–ones
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An effort to include biologically potent benzotriazole nucleus into piperidine ring is achieved through hydrazone formation. The characterization of the synthesized compounds was carried out using FT-IR, 1H &13C NMR, 1H–1H COSY, 1H–13C COSY, NOESY spectral techniques and GC-Mass spectrum. The spectral assignments were done without ambiguity using 2D-NMR techniques. The conformational preference of the piperidine ring deduced from the spectral studies is ‘chair’. The diastereotopic nature of the methylene protons/methyl groups present in the molecules is revealed clearly in their spectral pattern observed.
- Pillai, M. Velayutham,Rajeswari,Kumar, C. Udhaya,Krishnan, K. Gokula,Mahendran,Ramalingan,Nagarajan,Vidhyasagar
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p. 558 - 565
(2017/09/19)
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- Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d] -[1,2,3]triazole derivatives using 1H-benzo[d][1,2,3]triazole as starting material
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A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2-14) have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d][1,2,3] triazole (1) as starting material. The reaction of benzotriazole 1 with chloroacetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotriazole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate afforded ester 4, which was treated with hydrazine hydrate to afford the corresponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide afforded the nitro-glycoside derivative 6, which was deacetylated using methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dianhydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9, respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to give potassium salt 10, which was reacted with hydrazine hydrate to afford aminotriazole derivative 11. The latter compound was reacted with carbon disulphide to afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the thioglycoside 13 using methanolic ammonia solution at room temperature afforded the deprotected thioglycoside 14. The antimicrobial screening of some synthesized compounds showed that many of these compounds have good antimicrobial activities comparable to streptomycin and fusidic acid as reference drugs.
- Ali, Omar M.,Amr, Abd El-Galil E.,Mostafa, Elsayed E.
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p. 1545 - 1556
(2014/05/06)
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- MW assisted synthesis of some pyrazoles containing benzotriazole moiety: An environmentally benign approach
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MW assisted synthesis of pyrazoles containing benzotriazole moieties 4a-n has been achieved by cyclocondensation of substituted chalcones 3a-n with hydrazide of benzotriazole 2 in presence of glacial acetic acid (GAA). Thus, synthesized compounds 4a-n have been characterized by their spectral data and evaluated for their antibacterial and antifungal activities against various microbes.
- Tiwari, Urvashi,Ameta, Chetna,Rawal, Manish K.,Ameta, Rakshit,Punjabi, Pinki B.
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p. 432 - 439
(2013/05/08)
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- Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity
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1,3,4-Oxadiazole derivatives have drawn continuing interest over the years because of their varied biological activities. In order to search for novel anticancer agents, we designed and synthesized a series of new 1,3,4-oxadiazole derivatives containing benzotriazole moiety as potential focal adhesion kinase (FAK) inhibitors. All the synthesized compounds were firstly reported. Among the compounds, compound 4 shows the most potent inhibitory activity against MCF-7 and HT29 cell lines with IC50 values of 5.68 μg/ml and 10.21 μg/ml, respectively. Besides, all the compounds were assayed for FAK inhibitory activity using the TRAP-PCR-ELISA assay. The results showed compound 4 exhibited the most potent FAK inhibitory activity with IC50 values of 1.2 ± 0.3 μM. Docking simulation by positioning compound 4 into the FAK structure active site was performed to explore the possible binding mode. Apoptosis which was analyzed by flow cytometry, demonstrated that compound 4 induced apoptosis against MCF-7 cells. Therefore, compound 4 may be a potential anticancer agent against MCF-7 cancer cell.
- Zhang, Shuai,Luo, Yin,He, Liang-Qiang,Liu, Zhi-Jun,Jiang, Ai-Qin,Yang, Yong-Hua,Zhu, Hai-Liang
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p. 3723 - 3729
(2013/07/19)
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- A New class of anticonvulsants possessing 6 hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides
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A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides was designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotarod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1Hbenzotriazol-1-yl) acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. None of the compounds exhibited neurotoxicity. A computational study was carried out for the calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.
- Kumar, Praveen,Tripathi, Laxmi
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experimental part
p. 337 - 348
(2012/08/28)
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- Substituted [1,3,4]-oxadiazole, [1,3,4]-thiadiazole and [1,2,4]-triazole; synthesis, characterization and antimicrobial study
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Series of compounds 5-(benzotriazol-1-yl-methyl)-2-aryl/alkyl-amino-[1,3,4] -oxadiazoles, 5-(benzotriazol-1-yl-methyl)-2-aryl/alkyl-amino-[1,3,4]- thiadiazoles and 5-(benzotriazol-1-yl-methyl)-3-mercapto-4-aryl/alkyl-4H-[1,2,4] -triazoles have been synthesized by the oxidative cyclization of 2-benzotriazol-1-yl-N-aryl/alkyl thiocarbamido-acetamides using alkaline ethanolic solution of iodine containing potassium iodide, ortho-phosphoric acid and aqueous potassium hydroxide solution respectively. These compounds on acetylation afforded acetyl derivatives, on benzoylation afforded benzoyl derivatives and on reaction with ethyl iodide afforded ethylmercapto derivatives. These compounds have been assayed for their antimicrobial activity against Gram-positive as well as Gram-negative microorganisms.
- Deohate, Pradip P.
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p. 253 - 259
(2012/11/06)
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- Substituted [1,2,4,5]-dithiadiazines and [1,3,4]-thiadiazolidines; synthesis, characterization and antimicrobial study
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Series of compounds 2-benzotriazol-1-yl-1-(3-phenylimino-6-aryl/alkylimino- [1,2,4,5]-dithiadiazinan-4-yl)-ethanones and 2-benzotriazol-1-yl-1-(2- phenylimino-5-aryl/alkylimino-[1,3,4]-thiadiazolidin-3-yl)-ethanones have been synthesized by the interaction of 2-benzotriazol-1-yl-N-aryl/alkyl thiocarbamido-acetamides with N-phenyl-S-chloro isothiocarbamoyl chloride and N-phenyl isocyanodichloride respectively. These compounds on acetylation afforded acetyl derivatives. The title compounds have been assayed for their antimicrobial activity against Gram-positive as well as Gram-negative microorganisms.
- Deohate, Pradip P.
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p. 1705 - 1710
(2013/08/24)
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- Synthesis and biological activity test of some new five membered heterocycles
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A new series of 1,3,4-oxadiazoles, 1,2,4-triazoles, 1,3,4-thiadiazoles were synthesized using alkylhydrazides as the starting materials, and then 1,2,4-triazoles were used to synthesize [1,2,4]triazolo[3,4-b][1,3,4] thiadiazoles. All the compounds were evaluated for in vitro antibacterial activity and antitumor activity. A new series of five membered heterocyclic compounds were synthesized using alkylhydrazides as the starting materials. All the compounds were evaluated for in vitro antibacterial activity and antitumor activity.
- Xia, Qingchun,Xu, Dongfang,He, Qizhuang,Li, Xingyu,Sun, Dazhi
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p. 2433 - 2440
(2011/10/05)
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- Synthesis of some new 5-[2-{(1,2,3-benzotriazole)-1- Yl-methyl}-1′- (4′-substituted aryl-3′-chloro-2′-oxo azetidine)]-amino-1,3,4- thiadiazoles: Antifungal and antibacterial agents
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As a part of systematic investigation of synthesis and biological activity, several new 5-[2-(1,2,3-benzotriazole)-1-yl-methyl]-arylidene hydrazino-1,3,4-thiadiazoles 7 and 5-[2-{(1,2,3-benzotriazole)-1-yl-methyl}- 1′-(4′-substituted aryl-3′-chloro-2′-oxo
- Shukla,Srivastava
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p. 463 - 469
(2008/09/20)
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- Synthesis of some new 3-(1,2,3-benzotriazolylmethyl)-4-(3-chloro-4- substituted aryl-2-oxo-azetidine)-5-mercapto-1,2,4-triazoles: Antifungal and antibacterial agents
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1,2,3-Benzotriazole on treatment with ethyl chloroacetate gave ethyl 1,2,3-benzotriazole-1-acetate 1 which on amination with hydrazine hydrate afforded 1,2,3-benzotriazole-1-acetic acid hydrazide 2. The compound 2 on cyclisation with CS2-KOH yi
- Nema,Srivastava
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p. 1037 - 1041
(2008/09/20)
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- Synthesis of 5-arylidene-2-aryl-3-(benzotriazoloacetamidyl)-1,3- thiazolidin-4-ones as analegesic and antimicrobial agents
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Benzotriazole on reaction with ethyl chloroacetate affords 1, which on treatment with hydrazine hydrate yields 2. Condensation of N 1(acetohydrazido)benzotriazole 2 with various carbonyls gives arylidene acetohydrazido benzotriazoles 3 which on
- Asati,Srivastava,Srivastava
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p. 526 - 531
(2007/10/03)
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- Synthesis of 5-arylidene-2-aryl-3-(phenothiazino/benzotriazoloacetamidyl)-1,3-thiazolidine-4-ones as antiimflammatory, anticonvulsant, analgesic and antimicrobial agents
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Condensation of N10(acetohydrazido) phenothiazine/benzotriazole 5, 6 with various carbonyls give arylidene acetohydrazido phenothiazines/benzotriazoles 7, 8 which on cycloaddition with mercapto acetic acid yield the corresponding 4-thiazolidino
- Mishra, Seema,Srivastava, S. K.,Srivastava, S. D.
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p. 826 - 830
(2007/10/03)
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- SYNTHESIS AND CHARACTERIZATION OF METAL COMPLEXES DERIVED FROM POTASSIUM 3-(BENZOTRIAZOLE-1-CARBONYLMETHYL)-DITHIOCARBAZATE
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The preparation and characterization of some dipositive metal ion complexes derived from potassium 3-(benzotriazole-1-carbonylmethyl)-dithiocarbazate (BCDHK) is reported.The solid complexes of the composition ML*nH2O (M=Mn(II), Ni(II), Cu(II), Cd(II), Zn(II) and Co(II), n=0,1) and ML2*2H2O (M=Pb(II), UO2(VI)), have been characterized on the basis of elemental analyses, IR, UV and TGA.IR spectral data indicate that BCDHK behaves as either a mononegative or binegative ligand and coordinates in a tridentate or bridging tetradentate manner.
- Xu, Peng-Fei,Liu, Zhang-Lu,Wu, Shao-Zu
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p. 579 - 584
(2007/10/02)
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