Design, synthesis, molecular docking and antiproliferative activity of some novel benzothiazole derivatives targeting EGFR/HER2 and TS

Abdellatif, Khaled R.A.; Belal, Amany; El‐Saadi, Mohammed T.; Amin, Noha H.; Said, Eman G.; Hemeda, Loah R.

doi:10.1016/j.bioorg.2020.103976

Cited by 42 publications

(14 citation statements)

References 59 publications

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“…Compounds 10 and 11 are analogues of benzothiazole linked to triazole as potent inhibitors of the EGFR kinase reported by Rezki et al [38] Both compounds showed IC 50 Compounds 12 and 13 have been reported as potent EGFR kinase inhibitors by Abdellatif et al [39] Both compounds showed potent EGFR-inhibitory activity, with IC 50 values of 1.08 and 0.432 µM, respectively. The cytotoxicity of compounds 12 and 13 was also found to be promising against A549, HCT-116, PC-3, and MCF-7 cancer cell lines, with IC 50 values below 2.35 µM.…”

Section: Egfr Inhibitorsmentioning

confidence: 95%

Advances in 2‐substituted benzothiazole scaffold‐based chemotherapeutic agents

Haider

Rehman

Pathak

et al. 2021

Archiv der Pharmazie

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Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential.Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold-based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture-based derivatives as potent anticancer agents.

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Section: Egfr Inhibitorsmentioning

confidence: 95%

Advances in 2‐substituted benzothiazole scaffold‐based chemotherapeutic agents

Haider

Rehman

Pathak

et al. 2021

Archiv der Pharmazie

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“…All of the experiments were accomplished in triplicates, and the viable cell average was determined. Using the formula used by Abdellatif et al, the percentage cell viability was calculated as follows c ell viability ( % ) = false( normaloptical density of the sample − normaloptical density of control false) normaloptical density of control × 100 Prism software was used for plotting the graph b/w the cell viability and dilutions.…”

Section: Methodsmentioning

confidence: 99%

“…All of the experiments were accomplished in triplicates, and the viable cell average was determined. Using the formula used by Abdellatif et al, 45 the percentage cell viability was calculated as follows In PBS + 2% FBSS, a mono cell suspension was formed after harvesting the cells. They were then resuspended at 3−6 × 10 6 cells per mL after the MCF-7 cells were washed and spun at 300× g for 5 min.…”

Section: Ethyl 2-(2-(2-(4-fluorophenyl)-2-oxoethyl)-3-oxo-2h-benzo[b]...mentioning

confidence: 99%

Synthesis, Molecular Docking, and Biological Evaluation of a New Series of Benzothiazinones and Their Benzothiazinyl Acetate Derivatives as Anticancer Agents against MCF-7 Human Breast Cancer Cells and as Anti-Inflammatory Agents

et al. 2023

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Six 1,4-benzothiazin-3-ones (2a–f) and four benzothiazinyl acetate derivatives (3a–d) were synthesized and characterized by various spectroscopic methods, namely, 1H NMR, 13C NMR, IR, MS, and elemental analysis. The cytotoxic effects of the compounds were assessed against MCF-7, a human breast cancer cell line, along with their anti-inflammatory activity. Molecular docking studies performed against the VEGFR2 kinase receptor displayed a common binding orientation of the compounds in the catalytic binding pocket of the receptor. The generalized Born surface area (GBSA) studies of compound 2c with the highest docking score also proved its stability in binding to the kinase receptor. Compounds 2c and 2b showed better results against VEGFR2 kinase with IC50 values of 0.0528 and 0.0593 μM, respectively, compared to sorafenib. All of the compounds (2a–f and 3a–d) showed effective growth inhibition having (IC50) values of 2.26, 1.37, 1.29, 2.30, 4.98, 3.7, 5.19, 4.50, 4.39, and 3.31 μM, respectively, against the MCF-7 cell line compared to standard 5-fluorouracil (IC50 = 7.79 μM). However, compound 2c displayed remarkable cytotoxic activity (IC50 = 1.29 μM), suggesting it as a lead compound in the cytotoxic assay. Additionally, compounds 2c and 2b showed better results against VEGFR2 kinase with IC50 values of 0.0528 and 0.0593 μM, respectively, compared to sorafenib. It also inhibited hemolysis by stabilizing the membrane comparable to that of diclofenac sodium, a standard used in the human red blood cell membrane stabilization assay and hence can act as a template for designing novel anticancer and anti-inflammatory agents.

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“…14 Previous studies have reported that incorporation of different heterocycles in the skeleton has shown significant inhibition of TS. For example, derivatives containing pyrimidine-indole, 15,16 N -phenyl-(2,4-dihydroxy pyrimidine-5-sulfonamido)phenyl urea, 17 pyrrolo-pyrimidine, 18–20 cyanopyrimidine, 21 benzothiazole, 22 phenolnaphthalein 23 and thiouracil 24 displayed promising inhibition of TS. In this context, benzimidazole is a promising scaffold that is present in numerous anticancer drugs with diverse modes of action.…”

Section: Introductionmentioning

confidence: 99%