Quinoline–1,3,4-Oxadiazole Conjugates: Synthesis, Anticancer Evaluation, and Molecular Modelling Studies

Nosipho Cele, Paul Awolade, Sanjeev Dhawan, Lungisani Khubone, Asif Raza, Arun K. Sharma, Parvesh Singh

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer continues to have overwhelming impacts on human health and the development of new chemotherapeutics. Molecular hybridization has thus been valued as a structure-based drug design approach to drugs with enhanced efficacy. Herein, we report the multistep synthesis of quinoline–2-mercapto-1,3,4-oxadiazole conjugates and their cytotoxicity evaluation. Compound 4j 2-[(5-bromopentyl)thio]-5-[(quinolin-8-yloxy)methyl]-1,3,4-oxadiazole showed the best cytotoxicity to pancreatic (MIA PaCa-2) and colorectal (HCT116) cancer cells with IC50 values of 29.19 ± 0.99 and 75.10 ± 1.87 µM, respectively. The compound is also less cytotoxic to non-cancerous human primary dermal fibroblast cells with IC50 = 91.87 ± 1.29 µM compared to the parent compound 8-hydroxyquinoline (IC50 = 72.36 ± 4.23 µM). ADME properties prediction suggested the drug-likeness of potent compounds while molecular docking and molecular dynamics simulations with doublecortin-like kinase (DCLK1) revealed the compounds’ stable binding interactions at the kinase domain. Overall, the results illuminate compound 4j as a structural model to furnish new cytotoxic agents against pancreatic and colorectal cancer.

Original languageEnglish (US)
Pages (from-to)6437-6457
Number of pages21
JournalPolycyclic Aromatic Compounds
Volume43
Issue number7
DOIs
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • Materials Chemistry
  • Polymers and Plastics
  • Organic Chemistry

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