Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents

Eldehna, Wagdy M.; Altoukhy, Ayman; Mahrous, Hoda; Abdel‐Aziz, Hatem A.

doi:10.1016/j.ejmech.2014.12.010

Cited by 89 publications

(41 citation statements)

References 55 publications

(56 reference statements)

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“…Synthesis of 5-Bromo-3-hydrazonoindolin-2-one To a stirred solution of 5-bromoisatin (2.26 g, 10 mmol) in methanol (20 mL), 99% hydrazine hydrate (2.5 mL, 50 mmol) was added. The reaction mixture was refluxed for 1 h. The precipitate was filtered, washed with methanol, and dried to afford 5-bromo-3-hydrazonoindolin-2-one [28] in almost quantitative yield.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

et al. 2017

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As part of the research endeavors to combat cancer, a non-symmetric bis-isatin derivative (compound 3) was synthesized and showed a significant anti-proliferative potency. The current study provides a comprehensive characterization of the interaction of compound 3 with the drug-transporting protein bovine serum albumin (BSA) via the use of spectroscopic tools along with molecular docking studies. Fluorescence spectral measurements showed that the BSA intrinsic fluorescence can be significantly quenched by the addition of compound 3 and the formation of a non-fluorescent complex. Further measurements revealed a static type of quenching with Stern-Volmer and Linweaver-Burk constants of 10 5 . The thermodynamic parameters of the binding were calculated to be ∆S • 105.09 ± 5.32 with ∆H • of −0.72 ± 0.71 and negative ∆G • values. In addition, synchronous fluorescence and 3D fluorescence spectroscopy suggested that compound 3 did not induce conformational changes in BSA. Site competition experiments revealed that compound 3 competes with warfarin within the BSA binding domain (Sudlow site I). This was further confirmed by the molecular docking results showing a binding energy of −25.93 kJ/mol for compound 3-BSA. Hence, the observed results in the present study assumed that the compound 3-BSA binding is spontaneous, involving electrostatic forces and hydrogen bonding.

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Section: Chemistrymentioning

confidence: 99%

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

et al. 2017

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“…In 2015, Eldehna et al [44] synthesized certain isatin-pyridine hybrids as potential anti-proliferative agents, four of these compounds 24a-d are 3-hydrazino-2-indolinone derivatives (Figure 15). Compounds 24b and 24c showed good activity against HepG2 cancer cell line with IC 50 = 11.5 and 8.7 µM, respectively.…”

Section: Figure 15mentioning

confidence: 99%

3-Hydrazinoindolin-2-one derivatives: Chemical classification and investigation of their targets as anticancer agents

Ibrahim

Abou‐Seri

Abdel‐Aziz

2016

European Journal of Medicinal Chemistry

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“…Regarding these points and as a continuation of our research program on the design and synthesis of effective antitumor candidates [29,30,31,32,33,34,35], it was thought worthwhile to extend our investigations around our study [28] to probe for benzimidazole derivatives having anti-proliferative activity towards TNBC. Our structure-based design was three-fold: (i) preserving benzimidazole structure with subsitution at 2-position; (ii) maintaining a terminal lipophilic group; and (iii) establishing a three-atom thio ethane-1-one linker to afford more flexibility for the designed molecules (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

Abdel‐Aziz

Eldehna

Ghabbour

et al. 2016

IJMS

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On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.

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Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents

Cited by 89 publications

References 55 publications

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

3-Hydrazinoindolin-2-one derivatives: Chemical classification and investigation of their targets as anticancer agents

Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

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