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 Ariffin
  • Zanariah Abdullah
  • Mahmood Ameen Abdulla
  • John Kwong Siew Shia
  • Kok Hoong Leong
Original Research
  • 519 Downloads

Abstract

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.

Keywords

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

Abbreviations

BDH

bond-dissociation enthalpies

BxPC-3

human primary pancreatic adenocarcinoma

CoQ

coenzyme q10

δ

chemical shift in parts per million

J

coupling constant (in nmr spectrometry)

DPPH

2,2-diphenyl-1-picrylhydrazyl radical

FRAP

ferric ion reducing antioxidant power

HBA

number of hydrogen bond acceptor

HBD

number of hydrogen bond donor

HAT

hydrogen atom transfer

hTERT-HPNE

normal pancreas cell line

IC50

half-maximum inhibitory concentration

log p

logarithm of partition coefficient

MCF-7

human breast adenocarcinoma cells

MDA-MB-231

human breast adenocarcinoma

MTT assay

cell proliferation colorimetric assay

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
  • Zanariah Abdullah
    • 1
  • Mahmood Ameen Abdulla
    • 3
  • John Kwong Siew Shia
    • 4
  • Kok Hoong Leong
    • 5
    • 6
  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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