Synthesis and Biological Evaluation of 5-Formyl-6-arylimidazo(2,1-b)-1,3,4-thiadiazole-2-N-(dimethylaminomethino)sulfonamides as Antitumor Agents

Gadad, Andanappa K.; Karki, Subhas S.; Rajurkar, Vikas G.; Bhongade, Bhoomendra A.

doi:10.1055/s-0031-1300515

Cited by 12 publications

(11 citation statements)

References 4 publications

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“…Later, antitumor activity of 5-formyl-6-arylimidazo-[2,1-b]-1,3,4-thiadiazole sulfonamides were also reported [20]. Based on these promising results, we synthesized a series of analogues containing fluorine at position 4 of 6-phenyl in imidazo-[2,1-b]-1,3,4-thiadiazole and identified 4a as the lead compound [21].…”

Section: Introductionmentioning

confidence: 97%

Novel Levamisole Derivative Induces Extrinsic Pathway of Apoptosis in Cancer Cells and Inhibits Tumor Progression in Mice

et al. 2012

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BackgroundLevamisole, an imidazo(2,1-b)thiazole derivative, has been reported to be a potential antitumor agent. In the present study, we have investigated the mechanism of action of one of the recently identified analogues, 4a (2-benzyl-6-(4′-fluorophenyl)-5-thiocyanato-imidazo[2,1-b][1], [3], [4]thiadiazole).Materials and MethodsROS production and expression of various apoptotic proteins were measured following 4a treatment in leukemia cell lines. Tumor animal models were used to evaluate the effect of 4a in comparison with Levamisole on progression of breast adenocarcinoma and survival. Immunohistochemistry and western blotting studies were performed to understand the mechanism of 4a action both ex vivo and in vivo.ResultsWe have determined the IC50 value of 4a in many leukemic and breast cancer cell lines and found CEM cells most sensitive (IC50 5 µM). Results showed that 4a treatment leads to the accumulation of ROS. Western blot analysis showed upregulation of pro-apoptotic proteins t-BID and BAX, upon treatment with 4a. Besides, dose-dependent activation of p53 along with FAS, FAS-L, and cleavage of CASPASE-8 suggest that it induces death receptor mediated apoptotic pathway in CEM cells. More importantly, we observed a reduction in tumor growth and significant increase in survival upon oral administration of 4a (20 mg/kg, six doses) in mice. In comparison, 4a was found to be more potent than its parental analogue Levamisole based on both ex vivo and in vivo studies. Further, immunohistochemistry and western blotting studies indicate that 4a treatment led to abrogation of tumor cell proliferation and activation of apoptosis by the extrinsic pathway even in animal models.ConclusionThus, our results suggest that 4a could be used as a potent chemotherapeutic agent.

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Section: Introductionmentioning

confidence: 97%

Novel Levamisole Derivative Induces Extrinsic Pathway of Apoptosis in Cancer Cells and Inhibits Tumor Progression in Mice

et al. 2012

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“…They are also used as the carbonic anhydrase inhibitors. Some of them have revealed the antimycobacterial, anesthetic, antidepressant, and anxiolytic activity . Several compounds containing 1,3,4‐thiadiazole ring are well known drugs .…”

Section: Introductionmentioning

confidence: 99%

The Studies of Structure of 2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] Thiadiazol‐2‐yl) Amine in Solution

Strzemecka

Fijałkowski

Nowaczyk

2016

Journal of Heterocyclic Chem

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2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] thiadiazol‐2‐yl) amine was studied by means of the 1H, 13C, 15N NMR spectroscopy and DFT calculations. On the basis of the one‐dimensional 1H, 13C, 15N‐NMR and two‐dimensional 1H‐13C HMQC, 1H‐13C HMBC, 1H‐15N HMQC, 1H1H NOESY, 1H1H COSY correlation spectra the amine‐type and the imine‐type tautomers have been determined in the solution. Variety of structural forms including: biradical, ionic–biradical, and ionic structures of the amine‐type a and of the imine‐type b, c tautomers exist in the solution. According to the DFT computations the differences in the total energy between a and b, a and c, and b and c tautomers are equal to 1.5 kJ/mol, 1.2 kJ/mol, and 0.3 kJ/mol, respectively.

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“…Imidazothiadiazoles show a wide spectrum of biological properties like antibacterial, 9 antifungal, 10 antitubercular 11 and anticancer. [12][13][14][15][16] Imidazothiadiazoles display different types of molecular mechanisms in cancer chemotherapy. [13][14][15][16][17][18] Previous work on 2-amino-1,3,4-thiadiazole analogues reports the activity of these compounds against numerous transplanted animal tumours.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of imidazothiadiazole–benzimidazole conjugates as mitochondrial apoptosis inducers

et al. 2014

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A series of imidazothiadiazole-benzimidazole conjugates (3a-z) were synthesized and evaluated for their cytotoxic activity against a set of four selected human cancer cell lines. Amongst them, compounds 3b and 3y exhibited significant antiproliferative activity in ME-180 (cervical) cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G 0 /G 1 phase leading to the loss of mitochondrial membrane potential followed by apoptotic cell death. Further, Hoechst 33258 staining, DNA fragmentation assay, Annexin V staining assay and caspase-3 also suggested that 3b and 3y induced cell death by apoptosis. Docking studies revealed that compound 3b binds to the Gly142, Phe101, Asn140 and Arg143 on B-cell lymphoma 2 (Bcl-2) proteins and inhibition of Bcl-2 protein could be the possible mechanism of action for these compounds.

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Synthesis and Biological Evaluation of 5-Formyl-6-arylimidazo(2,1-b)-1,3,4-thiadiazole-2-N-(dimethylaminomethino)sulfonamides as Antitumor Agents

Cited by 12 publications

References 4 publications

Novel Levamisole Derivative Induces Extrinsic Pathway of Apoptosis in Cancer Cells and Inhibits Tumor Progression in Mice

Novel Levamisole Derivative Induces Extrinsic Pathway of Apoptosis in Cancer Cells and Inhibits Tumor Progression in Mice

The Studies of Structure of 2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] Thiadiazol‐2‐yl) Amine in Solution

Synthesis of imidazothiadiazole–benzimidazole conjugates as mitochondrial apoptosis inducers

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