Medicinal Chemistry Research

, Volume 25, Issue 9, pp 2015–2029 | Cite as

Synthesis, characterization, drug-likeness properties and determination of the in vitro antioxidant and cytotoxic activities of new 1,3,4-oxadiazole derivatives

  • Nafal Nazarbahjat
  • Azhar AriffinEmail author
  • Zanariah Abdullah
  • Mahmood Ameen Abdulla
  • John Kwong Siew Shia
  • Kok Hoong LeongEmail author
Original Research


A series of new 1,3,4-oxadiazole derivatives were synthesized and evaluated for their antioxidant, cytotoxic, and apoptosis activities. Antioxidant activity was determined in vitro using free radical scavenging (2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power assays. Most of the synthesized compounds exhibited significant antioxidant activities. Compound 3 showed the most potent antioxidant activity, comparable to the antioxidants used as positive controls—quercetin, BHT, trolox, rutin, and ascorbic acid. Compound 1 displayed high radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl assay, with an half-maximum inhibitory concentration (IC50) = 2.22 ± 0.01 µg/mL. Cytotoxic activities were evaluated in vitro against three human cancer cell lines (BxPC-3, MCF-7, MDA-MB-231) and one normal cell line (hTERT-HPNE) using the MTT assay. Compound 4e showed the most potent cytotoxic activity against MDA-MB-231 (IC50 = 21.40 ± 1.22 µM), and compound 4c showed the most potent activity against BxPC-3 (IC50 = 26.17 ± 1.10 µM). Further investigation on BxPC-3 cells showed compound 4c induces apoptosis and cell cycle arrest at G0/G1 phase. The drug-likeness parameters of these oxadiazole derivatives were evaluated according to the Lipinski rule, the Veber rule, and Egan’s model. All of the derivatives were found to have good predicted absorption characteristics, with the exception of compound 4d due to its high lipophilicity.


1,3,4-oxadiazole Schiff bases Drug-likeness properties Antioxidant activity Cytotoxic activity Apoptosis 



bond-dissociation enthalpies


human primary pancreatic adenocarcinoma


coenzyme q10


chemical shift in parts per million


coupling constant (in nmr spectrometry)


2,2-diphenyl-1-picrylhydrazyl radical


ferric ion reducing antioxidant power


number of hydrogen bond acceptor


number of hydrogen bond donor


hydrogen atom transfer


normal pancreas cell line


half-maximum inhibitory concentration

log p

logarithm of partition coefficient


human breast adenocarcinoma cells


human breast adenocarcinoma

MTT assay

cell proliferation colorimetric assay



The authors would like to thank the University of Malaya for UMRG grants (RP021B-14AFR), PPP grant (PG033-2012B), PRPUM grant (CG021-2013) and the Ministry of Higher Education of Malaysia grant (FP024-2014A) for supporting this study. The authors acknowledge CRYSTAL for providing the computational resources for computational intensive calculation and model building.

Compliance with ethical standards

Conflict of Interest

The authors declare no conflicts of interest in this work.

Supplementary material

44_2016_1660_MOESM1_ESM.docx (19 kb)
Supplementary Information
44_2016_1660_MOESM2_ESM.docx (19 kb)
Supplementary Information


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Nafal Nazarbahjat
    • 1
    • 2
  • Azhar Ariffin
    • 1
    Email author
  • Zanariah Abdullah
    • 1
  • Mahmood Ameen Abdulla
    • 3
  • John Kwong Siew Shia
    • 4
  • Kok Hoong Leong
    • 5
    • 6
    Email author
  1. 1.Department of Chemistry, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  2. 2.Department of Medical AnalysisCollege of Health and Medical TechnologiesBaghdadIraq
  3. 3.Department of Biomedical Science, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  4. 4.Integrative Pharmacogenomics Institute (iPROMISE) Level 7, FF3 BuildingUniversiti Teknologi MARASelangorMalaysia
  5. 5.Department of Pharmacy, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  6. 6.Center for Natural Product and Drug Discovery (CENAR), Department of Chemistry, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia

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