Quinazoline based 1,3,5-triazine derivatives as cancer inhibitors by impeding the phosphorylated RET tyrosine kinase pathway: Design, synthesis, docking, and QSAR study
Corresponding Author
Prateek Pathak
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorVladislav Naumovich
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Search for more papers by this authorMaria Grishina
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Search for more papers by this authorParjanya Kumar Shukla
Sam Higginbottom University of Agriculture Technology and Sciences, Allahabad, Uttar Pradesh, India
Search for more papers by this authorCorresponding Author
Amita Verma
Sam Higginbottom University of Agriculture Technology and Sciences, Allahabad, Uttar Pradesh, India
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Vladimir Potemkin
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Prateek Pathak
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorVladislav Naumovich
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Search for more papers by this authorMaria Grishina
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Search for more papers by this authorParjanya Kumar Shukla
Sam Higginbottom University of Agriculture Technology and Sciences, Allahabad, Uttar Pradesh, India
Search for more papers by this authorCorresponding Author
Amita Verma
Sam Higginbottom University of Agriculture Technology and Sciences, Allahabad, Uttar Pradesh, India
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Vladimir Potemkin
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia
Correspondence Prateek Pathak and Vladimir Potemkin, Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Tchaikovsky str. 20-A, 454008 Chelyabinsk, Russia.
Email: [email protected] (PP) and [email protected] (VP)
Amita Verma, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, India 211007.
Email: [email protected]
Search for more papers by this authorAbstract
The present research focused on designing a quinazoline skeleton, framed via 1,3,5-triazine derivatives (QBT) through field mapping and alignment studies. The QBT derivatives were synthesized via time- and cost-effective protocol. The 3D-QSAR study, computational physicochemical properties, and ADME calculation of the derivatives were performed to establish the affinity towards the biological system. Molecular docking in the adenosine triphosphate binding site of the RET tyrosine kinase domain (PDB ID: 7IVU) was studied to elucidate vital structural residues necessary for bioactivity. The derivatives were evaluated for anticancer potency against TPC-1 cells (thyroid cancer), MCF-7 cells (breast cancer), and one normal cell line (human foreskin fibroblasts) via 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay followed by an in ovo CAM assay. The entire series of derivatives (8a–o) showed mild to significant anticancer potency against the selected cancer cell lines.
CONFLICT OF INTERESTS
The authors declared that there is no conflict of interests.
Supporting Information
| Filename | Description |
|---|---|
| ardp201900053-sup-0001-ArchPharm_SupplMat_InChI.doc86 KB | Supporting information |
| ardp201900053-sup-0002-NMR_data.docx4.7 MB | Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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