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In silico design of novel anticancer drugs with amino acid and carbohydrate building blocks to inhibit PIM kinases

Kalhor, S ; Sharif University of Technology | 2022

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  1. Type of Document: Article
  2. DOI: 10.1080/08927022.2022.2030862
  3. Publisher: Taylor and Francis Ltd , 2022
  4. Abstract:
  5. PIM-1 is a serine-threonine kinase mainly expressed in tissues like the Thymus, spleen, bone marrow, and liver. Overexpression of PIM kinases occurs in various types of human tumours, such as lymphomas, prostate cancer, and oral cancer. As a result, the design of drugs to inhibit PIM-1 in cancerous cells has attracted much attention in recent years. This study aimed to design the alternative inhibitors for PIM-1 kinase, which are based on carbohydrates and amino acids and are expected to be non-toxic with the same chemotherapeutic effects as the traditional known anticancer drugs. The combinatorial use of quantum mechanics (QM) and molecular dynamic simulation (MD) has enabled us to precisely predict the inhibition of PIM-1 kinase by the novel designed drugs and compare them with the recently synthesized chemotherapeutic drugs such as DBC (Table 1). All designed structures were optimized at the B3LYP/6-311++G(d,p) level. The designed structure UNK4 (Table 1) was the most similar structure to DBC in terms of volumes, areas, and electrostatic potential map to DBC. The results obtained in this research represented that UNK4, with the building blocks of amino acid and cyclic carbohydrates could be considered an alternative anticancer drug for DBC. © 2022 Informa UK Limited, trading as Taylor & Francis Group
  6. Keywords:
  7. Amino acid ; Cancer cells ; Molecular dynamic simulation ; Monosaccharides ; Amino acids ; Bone ; Carbohydrates ; Diseases ; Enzymes ; Quantum theory ; Amino-acids ; Anticancer drug ; Bone marrow ; Building blockes ; Cancer cells ; In-silico ; Overexpressions ; PIM-1 ; Silico design ; Threonine kinase ; Molecular dynamics
  8. Source: Molecular Simulation ; Volume 48, Issue 6 , 2022 , Pages 526-540 ; 08927022 (ISSN)
  9. URL: https://www.tandfonline.com/doi/full/10.1080/08927022.2022.2030862