Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity

Liao, Weike; Wang, Zhongyuan; Han, Yufei; Qi, Yinliang; Liu, Jiaan; Xie, Juan; Tian, Ye; Lei, Qiancheng; Chen, Rui; Sun, Ming; Tang, Lei; Gong, Guowei; Zhao, Yanfang

doi:10.1016/j.ejmech.2020.112309

Cited by 8 publications

(2 citation statements)

References 25 publications

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“…The IC 50 values for these compounds 16a 16 The structure of curcumin-resveratrol-Nacylhydrazones 16a-c CCNB1, PLK1, AURKA, and AURKB enzymes, while simultaneously increasing CDKN1A (p21). [73] Liao et al [74] developed a variety of new 2,3,4,5-tetrasubstituted thiophene derivatives with an N-acylarylhydrazone scaffold using a rational design technique for the isoform-selective inhibition of phosphatidylinositol 3-kinase (PI3Kα). The most effective molecule, 17 (Figure 17) had been refined to a level equivalent to PF-4989216 and displayed an IC 50 of 6.5 nM against PI3Kα.…”

Section: N-acylhydrazones As Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Kassab

2023

Archiv der Pharmazie

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The N-acylhydrazone motif has been shown to be particularly adaptable and promising in the area of medicinal chemistry and drug development, due to its significant biological and pharmacological characteristics. Moreover, N-acylhydrazones are appealing synthetic and biological tools because of their simple and straightforward synthesis. This scaffold has emerged as a fundamental building block for the synthesis of bioactive compounds.Particularly, the N-acylhydrazone scaffold served as a base for the synthesis of a number of potent anticancer agents acting via different mechanisms. An updated summary of the anticancer activity of N-acylhydrazone derivatives described in the literature (from 2017 to 2022) is provided in the current review. It discusses the structure-activity relationship (SAR) of N-acylhydrazone derivatives exhibiting anticancer potential, which could be helpful in designing and developing new derivatives as effective antiproliferative candidates in the future.

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Section: N-acylhydrazones As Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Kassab

2023

Archiv der Pharmazie

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“…Among the various isoforms of PI3K, PI3Kα over expression leads to the occurrence of various types of cancer like colon, brain, breast, endometrial tumors and non-small cell lung cancer (NSCLC). [52] Among different possible molecular targets, targeting PI3Kα will effectively inhibit NSCLC.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis, Spectroscopic (FT‐IR, FT‐Raman), Electronic Properties and Molecular Docking Studies of 1‐(2, 6‐dibromo‐4‐methyl‐phenoxymethyl)‐benzo[f]chromen‐3‐one

Hiremath¹,

Khemalapure²

2023

ChemistrySelect

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Herein, 1‐(2,6‐dibromo‐4‐methyl‐phenoxymethyl)‐benzo[f]chromen‐3‐one (DBMPBC) is chosen to be thoroughly investigated in terms of structural, spectroscopic (FT‐IR, FT‐Raman) and molecular electronic properties based on density functional theory (DFT). The title molecule is synthesized by the reaction of 5,6‐benzo‐4‐bromomethylcoumarin with 2,6‐dibromo‐4‐methylphenol in presence of anhydrous potassium carbonate in dry acetone. All the computational studies for the selected structure are carried out at the theoretical level DFT/B3LYP/6‐311++G (d, p). The theoretically determined geometrical parameters from optimized structure and experimental values are compared to each other to confirm the structural properties of the molecule. The vibrational wavenumbers are studied by FT‐IR and FT‐Raman spectral techniques in both experimental and computational methods and compared to each other. The detailed vibrational assignments are assigned through potential energy distribution method by VEDA. The MEP surface analysis is carried out in order to identify the potential sites of electrophilic and nucleophilic attack. The Natural Bond Orbital (NBO) study significantly verified the existence of the intermolecular interactions in the molecule. The stability and reactivity properties of the molecule are estimated in terms of HOMO‐LUMO energies. Molecular docking investigations are carried out to simulate the inhibitory impact of the title molecule against the VEGFR2 (PDB: 2XIR) and PI3K (PDB: 2RDO) receptors for anti‐angiogenic therapy in the treatment of NSCLC. ADMET parameters and toxicity properties of the title molecule is conducted.

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Five-membered ring systems: thiophenes and selenium/tellurium analogues and benzo analogues

Joule¹

2021

Progress in Heterocyclic Chemistry

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Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity

Cited by 8 publications

References 25 publications

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Anticancer agents incorporating the N‐acylhydrazone scaffold: Progress from 2017 to present

Synthesis, Spectroscopic (FT‐IR, FT‐Raman), Electronic Properties and Molecular Docking Studies of 1‐(2, 6‐dibromo‐4‐methyl‐phenoxymethyl)‐benzo[f]chromen‐3‐one

Five-membered ring systems: thiophenes and selenium/tellurium analogues and benzo analogues

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