Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies

Farghaly, Thoraya A.; Abbas, Eman M. H.; Alsoliemy, Amerah; Sabour, Rehab; Shaaban, Mohamed R.

doi:10.1016/j.bioorg.2022.105684

Cited by 28 publications

(13 citation statements)

References 42 publications

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Section: Introductionmentioning

confidence: 63%

“…13 C NMR (CDCl 3 ): 26.7 (CH 2 ), 28.3 (CH 2 ), 122.9, 125.7, 128.9, 130.8, 135.8, 150.4, 156.5, 178.7 (C = S). MS(m/z): 285 (M + +2, 29), 284 (M + +1, 6), 283 (M + , 27), 268 (15), 266 (14), 129 (10), 115 (67), 102 (31), 90 (8), 89 (42), 76 (39), 60 (100). Elemental Analysis (%): (C 10 H 10 BrN 3 S; Mwt: 284.18) Calc.…”

Section: Synthesis Of 2-(5-bromo-23-dihydro-1h-inden-1-ylidene)hydraz...mentioning

confidence: 99%

“…1 H NMR(850 MHz, CDCl 3 ): 2.56 (s, 3H, CH 3 ), 2.78 (t, J = 8.5 Hz, 2H, CH 2 ), 3.16 (t, J = 8.5Hz, 2H, CH 2 ), 6.93 (t, J = 8.5Hz,1H, ArH), 7.17 (d, J = 8.5 Hz, 2H, ArH), 7.33 (t, J = 8.5Hz, 2H, ArH), 7.45-7.50 (m, 3H, ArH), 8.47 (s, 1H, NH), 11.62 (s, 1H, NH). MS(m/z): 384 (M + , 3), 212 (5), 210 (8), 176 (14), 115 (26), 105 (34), 102 (17), 92 (25), 77 (100), 70 (12) (45), 115 (59), 111 (100), 99 (45), 89 (16), 75 (40), 70 (27), 63 (23), 51 (10) MS(m/z): 463 (M + +2, 1), 462 (M + +1, 1), 461 (M + ,1), 147 (7), 129 (9), 120 (24), 115 (14), 107 (23), 102 (10), 92 (31), 77 (100), 65 (23), 51 (12)…”

Section: N'-(5-bromo-23-dihydro-1h-inden-1-ylidene)-2-oxo-n''-phenylp...mentioning

confidence: 99%

“…Cyclic formazan derivatives are good indicators, especially for lithium-ion in blood [ 30 ]. Combining all the above findings with our research project concerning the synthesis of bioactive heterocyclic compounds [ 31 – 35 ], we focused on synthesizing a new series of thiazole and formazan derivatives and then investigating their anti-gastric and anti-colon cancer activities.…”

Section: Introductionmentioning

confidence: 99%

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Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

2023

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Two new series of thiazole and formazan linked to 5-Bromo-indan were synthesized, and their structures were assured based on all possible analytical techniques. The size of the tested derivatives was calculated from the XRD technique and found five derivatives 3, 10a, 14a, 15, and 16 on the nanosized scale. The two series were tested for their efficacy and toxicity as anti-colon and stomach cancers. Derivative 10d showed activity more than the two reference drugs used in the case of SNU-16. Surpislly, in the case of COLO205, five derivatives 4, 6c, 6d, 6e, and 10a are better than the two benchmarks used, and two derivatives, 14a and 14b more potent than cisplatin. All potent derivatives showed a strong fit with the active site of the two tested proteins (gastric cancer (PDB = 2BID) and colon cancer (PDB = 2A4L)) in the molecular docking study. The Pharmacophore and ADME studies of the new derivatives showed that most derivatives revealed promising bioactivity, which indicates the drug-likeness properties against kinase inhibitors, protease, and enzyme inhibitors. In addition, the ProTox-II showed that the four compounds 10d, 16, 6d, and 10a are predicted to have oral LD50 values ranging from 335 to 3500 mg/kg in a rat model with (1 s,4 s)-Eucalyptol bearing the highest values and quercetin holding the lowest one.

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Section: Introductionmentioning

confidence: 63%

Section: Synthesis Of 2-(5-bromo-23-dihydro-1h-inden-1-ylidene)hydraz...mentioning

confidence: 99%

Section: N'-(5-bromo-23-dihydro-1h-inden-1-ylidene)-2-oxo-n''-phenylp...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

2023

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“…Besides, hydrazides‐hydrazones occupy a prominent place as versatile pharmacophores found in pharmacologically active molecules (Kumar & Narasimhan, 2013) and their unique structural features (e.g., presence of hydrogen bond donor and acceptor groups able to interact with crucial enzyme/receptor sites) (Mathew et al, 2015) make them suitable drug candidates for the targeted therapy of several diseases (Narang et al, 2012) including cancer (Bak et al, 2011; Han et al, 2019; Viswanathan et al, 2019). In particular, the molecular hybridization of the hydrazone motif with the thiazole scaffold has also resulted in the discovery of targeted anticancer agents (Altıntop et al, 2018; Chimenti et al, 2009; Farghaly et al, 2022; Narayanan et al, 2019; Secci et al, 2014; Wang et al, 2019; Zeytün et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A new series of thiazole‐hydrazone hybrids for Akt‐targeted therapy of non‐small cell lung cancer

Orujova

Ece

Çiftçi

et al. 2022

Drug Development Research

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In an attempt to identify potent antitumor agents for the fight against non-small cell lung cancer, new thiazolyl hydrazones (2a-n) were synthesized and examined for their in vitro cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells by means of the MTT assay. Furthermore, the effects of the most potent anticancer agents on apoptosis and Akt inhibition were investigated. 2-[2-((Isoquinolin-5yl)methylene)hydrazinyl]−4-(4-methylsulfonylphenyl)thiazole (2k) (IC 50 = 1.43 ± 0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]−4-(1,3-benzodioxol-5-yl)thiazole (2l) (IC 50 = 1.75 ± 0.07 µM) displayed more pronounced anticancer activity than cisplatin (IC 50 = 3.90 ± 0.10 µM) on A549 cell lines; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl] −4-(4-methoxyphenyl)thiazole (2j) (IC 50 = 3.93 ± 0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis in A549 cells.Compound 2j (IC 50 = 3.55 ± 0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC 50 = 4.93 ± 0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC 50 concentrations (1.43 and 1.75 µM, respectively). To comprehensively elucidate the binding pose of compound 2j and to provide a detailed understanding on the ligand' binding mechanism, induced-fit docking calculations were also conducted.Both in vitro and in silico studies suggest that compound 2j shows its cytotoxic and apoptotic effects on A549 cell lines via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways.

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Exploration of antiproliferative potential of modified triazole–benzohydrazone scaffold: Multitarget approach

Ali,

Khalaf,

Bhongade

et al. 2023

Archiv der Pharmazie

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A novel series of triazole–benzohydrazone hybrids was efficiently designed and synthesized as antiproliferative agents, targeting different kinases. All compounds were screened via the National Cancer Institute (NCI) against 60 cancer cell lines, where compounds 16, 17, and 18 exhibited growth inhibition percent (GI%) of various leukemia subpanels with values of 70.33%, 64.13%, and 76.03%, respectively. Compound 18 showed broad‐spectrum antiproliferative efficacy toward most cancer cells, with outstanding potency regarding melanoma (MALME‐3M GI% = 101.82%) and breast cancer cell lines (MCF7 GI% = 85.87%), while proving safe toward the WI‐38 normal cell line, compared to doxorubicin. Multikinase investigation including vascular endothelial growth factor receptor 2 (VEGFR‐2), mesenchymal epithelial transition factor (c‐Met), proto‐oncogene B‐Raf, mitogen‐activated protein kinase kinase, extracellular signal‐regulated kinase, and phosphoinositide 3‐kinase was accomplished to reveal its plausible mechanism of action, giving the ultimate potency against both VEGFR‐2 and c‐Met with IC50 values of 0.055 and 0.042 μM, respectively, while displaying moderate to good inhibition concerning the remaining kinases. DNA binding capability was excluded using the methyl green colorimetric assay. Further, it exhibited both early and late apoptotic induction by about 16‐ and 9.4‐fold over the control, respectively, triggering cell cycle arrest in the G2/M phase. Physicochemical properties and bioavailability radar plot inferred drug‐likeness characteristics for compound 18. The molecular docking study assessed the binding pattern with the active sites of c‐Met and VEGFR‐2.

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Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies

Cited by 28 publications

References 42 publications

Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

A new series of thiazole‐hydrazone hybrids for Akt‐targeted therapy of non‐small cell lung cancer

Exploration of antiproliferative potential of modified triazole–benzohydrazone scaffold: Multitarget approach

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