2. Academic Validation
  3. Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives

Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives

  • Eur J Med Chem. 2014 Sep 12:84:247-63. doi: 10.1016/j.ejmech.2014.07.024.
Veda Prachayasittikul 1,  Ratchanok Pingaew 2,  Apilak Worachartcheewan 3,  Chanin Nantasenamat 3,  Supaluk Prachayasittikul 4,  Somsak Ruchirawat 5,  Virapong Prachayasittikul 6
Affiliations

Affiliations

  • 1 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 2 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
  • 3 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 4 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand. Electronic address: supaluk@swu.ac.th.
  • 5 Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand; Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, Thailand.
  • 6 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand. Electronic address: virapong.pra@mahidol.ac.th.
PMID: 25019480 DOI: 10.1016/j.ejmech.2014.07.024
Abstract

A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3-12) were synthesized as Anticancer agents and tested against four Cancer cell lines including HepG2, HuCCA-1, A549 and MOLT-3. The most potent cytotoxic activity against the HepG2, HuCCA-1 and A549 cell lines was found to be m-acetylphenylamino-1,4-naphthoquinone (8) affording IC50 values of 4.758, 2.364 and 12.279 μM, respectively. On the Other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent cytotoxic activity against the MOLT-3 cell line with an IC50 of 2.118 μM. Quantitative structure-activity relationship (QSAR) investigations provided good predictive performance as observed from cross-validated R of 0.9177-0.9753 and RMSE of 0.0614-0.1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13-36) for which cytotoxic activities were predicted using equations obtained from the previously constructed QSAR models. Interpretation of informative descriptors from QSAR models revealed pertinent knowledge on physicochemical properties governing the cytotoxic activities of tested Cancer cell lines. It is anticipated that the QSAR models developed herein could provide guidelines for further development of novel and potent Anticancer agents.

Keywords

1,4-Naphthoquinone derivatives; Anticancer; QSAR; Structural modification.

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