Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies

Eldehna, Wagdy M.; Abo-Ashour, Mahmoud F.; Nocentini, Alessio; Gratteri, Paola; Eissa, Ibrahim H.; Farès, Mohamed; Ismael, Omnia E; Ghabbour, Hazem A.; Elaasser, Mahmoud M.; Abdel‐Aziz, Hatem A.

doi:10.1016/j.ejmech.2017.07.073

Cited by 114 publications

(39 citation statements)

References 51 publications

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“…It has been reported that tryptophan obtained from food sources is usually converted to indole by gastrointestinal bacteria, which is further oxidized in the liver by CYP450 to isatin, therefore, isatin is present as an endogenous molecule in humans [ 19 , 20 ]. Various substituents on the isatin nucleus displayed numerous biological activities [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], including antimicrobial activity[ 31 , 37 ], topoisomerase inhibitory activity [ 7 , 38 ], epidermal growth factor receptor (EGFR) inhibitory activity [ 39 ], inhibitory activities on histone deacetylase (HDAC) [ 40 , 41 ], carbonic anhydrase [ 42 , 43 , 44 ], tyrosine kinase [ 45 , 46 , 47 ], cyclin-dependent kinases (CDKs) [ 9 , 48 , 49 ], adenylate cyclase inhibition [ 50 ] and protein tyrosine phosphatase (Shp2) [ 51 ]. A number of isatin-based marketed drugs and potential anticancer agents [ 41 ] are illustrated in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

et al. 2020

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Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.

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Section: Introductionmentioning

confidence: 99%

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

et al. 2020

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“…Sulfonamide derivative 2 could decrease the cell viability of HT-29 cell line in a concentration dependent manner and with an IC 50 value of 5.45 mM 5 . Benzenesulfonamide 3 displayed a potent antiproliferative activity against MCF-7 cells with an IC 50 value of 3.96 mM as an apoptosis inducer 6 . Quinolinesulfonamide 4 exhibited the anticancer activity in vitro against T47D cells with an IC 50 value of 0.27 mM 7 .…”

Section: Introductionmentioning

confidence: 99%

Anticancer sulfonamide hybrids that inhibit bladder cancer cells growth and migration as tubulin polymerisation inhibitors

Liu

Zhang

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel sulfonamide-dithiocarbamate hybrids were designed and synthesised via the molecular hybridisation strategy. Among them, compound 13d displayed a potent activity with IC 50 values of 0.9, 0.7, 1.9 and 2.6 µM against UM-UC-3, RT-112, RT4 and T24. Compound 13d inhibited the migration and regulated the migration-related markers (E-cadherin, N-cadherin, Vimentin, Snail and Slung) against RT-112 cells in a concentration dependent manner. By the tubulin polymerisation assay in vitro and immunostaining assay, compound 13d was identified as a novel tubulin polymerisation inhibitor. Intragastric administration of compound 13d could inhibit the growth of RT-112 cells in vivo in a xenograft mouse model with the low toxicity, indicating that it may be a leading candidate with antitumor properties to treat bladder cancer.

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“…These results agreed with the previous reports where the bax/bcl-2 ratio is the major influential value to determine cell susceptibility to apoptosis. 35 However, treatment of HCT-116 cells by compounds 4c, 4d and 8c resulted in a significant elevation in the protein expression levels of active caspase-3 by about 2.59, 3.75 and 5 folds, respectively, compared to the nontreated HCT-116 control ( Figure 1C).…”

Section: Anticancer Activitymentioning

confidence: 89%

“…The analysis of the apoptotic markers Bax and caspase-3 levels as well as the anti-apoptotic marker Bcl-2 levels were assessed as reported earlier 35 for the most potent synthesized compounds on HCT-116 cells using ELISA colorimetric kits according to the manufacturer's instructions.…”

Section: Mechanistic Study On the Antitumor Activitymentioning

confidence: 99%

<p>One-Pot Synthesis of Novel Thiazoles as Potential Anti-Cancer Agents</p>

Sayed¹,

Gomha²,

Taher³

et al. 2020

DDDT

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Background: Thiazole and thiosemicarbazone derivatives are known to have potential anticancer activity with a mechanism of action related to inhibition of matrix metalloproteinases, kinases and anti-apoptotic BCL2 family proteins. Materials and Methods: A novel three series of 5-(1-(2-(thiazol-2-yl)hydrazono)ethyl) thiazole derivatives were prepared in a one-pot three-component reaction using 2-(2-benzylidene hydrazinyl)-4-methylthiazole as a starting precursor. MS, IR, 1 H-NMR and 13 C-NMR were used to elucidate the structures of the synthesized compounds. Most of the synthesized products were evaluated for their in vitro anticancer screening against HCT-116, HT-29 and HepG2 using the MTT colorimetric assay. Results: The results indicated that compounds 4c, 4d and 8c showed growth inhibition activity against HCT-116 with IC 50 values of 3.80 ± 0.80, 3.65 ± 0.90 and 3.16 ± 0.90 μM, respectively, compared to harmine (IC 50 = 2.40 ± 0.12 μM) and cisplatin (IC 50 = 5.18 ± 0.94 μM) reference drugs. Also, compounds 8c, 4d and 4c showed promising IC 50 values of 3.47 ± 0.79, 4.13 ± 0.51 and 7.24 ± 0.62 μM, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC 50 = 4.59 ± 0.67 μM) and cisplatin (IC 50 = 11.68 ± 1.54 μM). On the other hand, compounds 4d, 4c, 8c and 11c were the most active (IC 50 values of 2.31± 0.43, 2.94 ± 0.62, 4.57 ± 0.85 and 9.86 ± 0.78 μM, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC 50 = 2.54 ± 0.82 μM) and cisplatin (IC 50 = 41 ± 0.63 μM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds (4c, 4d and 8c) inside HCT-116 cells was apoptosis through the Bcl-2 family. Conclusion: Thiazole scaffolds 4c, 4d and 8c showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.

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Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies

Cited by 114 publications

References 51 publications

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

Anticancer sulfonamide hybrids that inhibit bladder cancer cells growth and migration as tubulin polymerisation inhibitors

<p>One-Pot Synthesis of Novel Thiazoles as Potential Anti-Cancer Agents</p>

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