Design, Synthesis, and Antitumor Activity of Novel 5-Pyridyl-1,3,4-oxadiazole Derivatives against the Breast Cancer Cell Line MCF-7

Khalil, Nadia A.; Kamal, Amr; Emam, Soha H.

doi:10.1248/bpb.b14-00867

Cited by 26 publications

(11 citation statements)

References 23 publications

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“…The binding sites were generated from the co‐crystallized ligand, within crystal protein (PDB codes: 4URO). [ 43 ] At first water, molecules have been removed from the complex. Then, crystallographic disorders and unfilled valence atoms were corrected using protein reports and utility and, the saved file was opened, 3D structures were protonated and energy was clean protein options.…”

Section: Methodsmentioning

confidence: 99%

New palladium (II) complexes with 1‐phenyl‐1H‐tetrazole‐5‐thiol and diphosphine Synthesis, characterization, biological, theoretical calculations and molecular docking studies

Al‐Janabi

Al-Samrai

Yousef

2020

Applied Organom Chemis

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This paper reports the syntheses and spectral investigations of the new complexes [Pd(k1‐S‐ptt)2(k2‐dppmS2)] (1), [Pd(k1‐S‐ptt)2(k2‐dppp)] (2a), [Pd(k1‐N‐ptt)2(k2‐dppp)] (2b), [Pd(k1‐S‐ptt)2(k2‐dpppS2)] (3), [Pd(k1‐S‐ptt)2(k2‐dppb)] (4), [Pd(k1‐S‐ptt)2(k2‐dppf)] (5a) and [Pd(k1‐N‐ptt)2(k2‐dppf)] (5b), derived from 1‐phenyl‐5‐thiol‐1H‐tetrazole (Hptt) and diphosphine (dppmS2, dppp, dpppS2, dppb and dppf) as co‐ligand. The Hptt ligand acts as monodentate through the thiolato sulfur atom in complexes 1, 3 and 4. While in complexes 2 and 5, the Hptt ligand also acts as monodentate through the nitrogen of heterocyclic ring, or sulfur of thiol group after deprotonation, as two linkage isomers. Theoretical calculations on the all complexes were performed, isomers based on 2a, 2b and 5a, 5b reveal that each pair of isomers is isoenergetic. For the 2a and 2b complexes the energy difference was 19.92 kcal mol−1, while for the 5a and 5b complexes the difference was 11.78 kcal mol−1. These differences are relatively small and suggest that the linkage isomers may be in equilibrium in solution. The reasons for the adoption of these different coordination modes are not clear but steric factors are likely to be a major contributory factor. Further, in vitro anti‐bacterial activity and molecular docking analysis has been carried out to study the activity of the compound.

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Section: Methodsmentioning

confidence: 99%

New palladium (II) complexes with 1‐phenyl‐1H‐tetrazole‐5‐thiol and diphosphine Synthesis, characterization, biological, theoretical calculations and molecular docking studies

Al‐Janabi

Al-Samrai

Yousef

2020

Applied Organom Chemis

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“…After selecting a protein for the target location, several processes were put forth to gain an understanding of the molecular binding modes of the tested compounds within the pocket of the epidermal growth factor receptor tyrosine kinase (ATP binding site of EGFR kinase) using the MOE 2015 Software. The binding sites were generated by co-crystallizing the ligand within the crystal protein (PDB code: 1M17) (Khalil et al 2015). Water molecules were first removed from the complex, and then crystallographic disorders, and unfilled valence atoms were corrected using protein report, and utility, and clean protein options.…”

Section: Molecular Docking Studymentioning

confidence: 99%

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

Abbas¹,

Mahmood²,

Tahtamouni³

et al. 2021

PHAR

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Thirteen new derivatives of picolinic acid (4–7) were designed and synthesized from the starting parent molecule, picolinic acid. The new compounds were characterized by ATR-FTIR, 1HNMR, and CHNS analysis. A molecular docking study was performed to evaluate the binding affinity of the synthesized compounds toward EGFR kinase domain that indicated occupation of the critical site of EGFR kinase pocket and excellent positioning of the compounds in the pocket. The cytotoxic activity of the compounds against two human cancer cell lines (A549 and MCF-7), the non-tumorigenic MCF10A cell line, and white blood cells (WBC) was evaluated using the MTT assay. Compound 5 showed anticancer activity against A549 lung cancer cells (IC50 = 99.93 µM) but not against MCF-7 breast cancer cells or normal cells. Compound 5 mediated cytotoxicity in A549 lung cancer cells by inducing apoptotic cell death, as suggested by fragmented nuclei after DAPI staining, and agarose gel electrophoresis. Moreover, compound 5 triggered the activation of caspases 3, 4 and 9. However, compound 5 treatment did not affect the release of cytochrome c from the mitochondria to the cytosol, as compared to the vehicle-treated control cells. Nevertheless, compound 5-treated cells reported greater release of smac/DIABLO to the cytosol. In the same context, both compound 5 and thapsigargin (specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)) enhanced eIF2 phosphorylation, reflecting the activation of the atypical ER stress pathway and the potential applicability of compound 5 in lung cancer treatment.

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“…oxadiazol-2-yl-methyl}-phenyl-amine (57) was found to be highest cytotoxic against Caco-2 cell lines (IC 50 = 2.3 μm) ( Figure 22) (Vinayak et al, 2017). Khalil et al (2015) designed 36 novel 5-pyridyl-1,3,4-oxadiazoles using computer-aided program, and then these designed compounds were synthesized to investigate the anticancer activity against breast cancer cell line MCF-7. However only two compounds, that is, compound N′-[(Z/E)-(3-Indolyl)methylidene]-2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl} acetohydrazide (58) and 4-Ethyl-N′-({[5-(pyridin-4-yl)-1,3,4oxadiazol-2-yl]sulfanyl}-acetyl)benzohydrazide (59), had shown comparable anticancer activity (i.e., IC 50 : 0.010 µm and 0.012 µm, respectively) with reference drug, that is, erlotinib.…”

Section: Pyridines Linked 134-oxadiazolesmentioning

confidence: 99%

1,3,4‐oxadiazole and its derivatives: A review on recent progress in anticancer activities

2020

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The 1,3,4-oxadiazole nucleus is a biologically imperative scaffold possesses numerous biological activities. The broad and potent activity of 1,3,4-oxadiazole and their derivatives has established them as important pharmacological scaffolds especially in the treatment of cancer disease. Several di-, tri-, aromatic, and heterocyclic substituted 1,3,4-oxadiazole derivatives have been reported to possess potent anticancer activity. These substituted 1,3,4-oxadiazoles had shown different mechanism of action and participated in anticancer drug discovery and development. This review is complementary to earlier reviews and aims to review the work reported on anticancer activities of 1,3,4-oxadiazole derivatives from year 2000 to the beginning of 2020. K E Y W O R D S 1,3,4-oxadiazole, cancer, histone deacetylase, synthesis, tubulin polymerizations | 573 VAIDYA et Al. anticancer evaluation of 1,3,4-oxadiazole derivatives as inhibitors of Kinesin spindle protein (KSP). KSP inhibitors have been utilized for the treatment of inflammation, hyperplasias, cancer, and immune disorders. Furthermore, Shashikumar and colleagues in year 2015 obtained a WO (World intellectual property organization) patent for 1,3,4-oxadiazoles as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signaling pathway. Theses patented compounds having the ability to boost the immunity and were reported as immunomodulators. The growing patent literature of recent years demonstrates that the 1,3,4-oxadiazoles are becoming of great practical significance. The literature clearly reported numerous mechanism for anticancer activities of substituted 1,3,4-oxadiazole derivatives (Zhang et al., 2010, 2011). Recently, Glomb et al. (2018) published a notable review article, describing antiproliferative effects of 1,3,4-oxadiazoles associated with their numerous mechanisms, including inhibition of growth factors, enzymes, kinases and others. Irrespective of Glomb et al. (2018) review in which they were cited numerous anticancer mechanism of 1,3,4-oxadiazoles, herein we had focused on several 1,3,4-oxadiazole derivatives for their anticancer activity. Especially, we focus this review on in vitro and in vivo anticancer activities of 1,3,4-oxadiazoles in the perspective of cancer drug development and refinement.

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Design, Synthesis, and Antitumor Activity of Novel 5-Pyridyl-1,3,4-oxadiazole Derivatives against the Breast Cancer Cell Line MCF-7

Cited by 26 publications

References 23 publications

New palladium (II) complexes with 1‐phenyl‐1H‐tetrazole‐5‐thiol and diphosphine Synthesis, characterization, biological, theoretical calculations and molecular docking studies

New palladium (II) complexes with 1‐phenyl‐1H‐tetrazole‐5‐thiol and diphosphine Synthesis, characterization, biological, theoretical calculations and molecular docking studies

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

1,3,4‐oxadiazole and its derivatives: A review on recent progress in anticancer activities

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