Vol.:(0123456789) 1 3
Cancer Chemother Pharmacol
DOI 10.1007/s00280-017-3414-6
SHORT COMMUNICATION
Inhibitory growth evaluation and apoptosis induction in MCF‑7
cancer cells by new 5‑aryl‑2‑butylthio‑1,3,4‑oxadiazole derivatives
Rashmin Khanam
1
· Kamal Ahmad
1
· Iram I. Hejazi
1
· Ibrar A. Siddique
2
·
Vikash Kumar
2
· Abdul Roouf Bhat
3
· Amir Azam
4
· Fareeda Athar
1
Received: 14 March 2017 / Accepted: 3 August 2017
© Springer-Verlag GmbH Germany 2017
involved in the attainment of cellular immortality and
carcinogenesis.
Result In vitro MTT screening assay showed the com-
pound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e)
showing the highest inhibitory efect against MCF-7 cancer
cell with IC
50
value 10.05 ± 1.08 µM while it is much safer
and less toxic on normal cell line (HEK-293). The dose-
dependent treatment of MCF-7 cells with 5e resulted in
inhibition of cell migration in the wound healing assay. The
fow-cytometry analysis showed the cells arrested in G0/
G1 phase of the cell cycle. Compound 5e induced apopto-
sis of MCF-7 cells was characterized using DAPI staining
and Annexin V-PE/7-AAD dual binding assay. Reduction
of NBT by compound 5e showed a reduced generation of
ROS. Western blotting studies showed high activation of
apoptotic protein Caspase3 and decrease in expression of
anti-apoptotic protein BCL-2.
Conclusion Based on the results of in vitro studies, it could
be concluded that compound 5e showed a signifcant inhibi-
tory growth efect on MCF-7 cells and have the potential to
be developed as lead molecule and further structural modif-
cations may result in promising new anticancer agents.
Abstract
Background Cancer has become one of the global health
issues and it is the life-threatening disease characterized by
unrestrained growth of cells. Despite various advances being
adopted by chemotherapeutic management, the use of the
current anticancer drugs such as Doxorubicin, Asparginase,
Methotrexate, Vincristine remains limited due to high tox-
icity, side efects and developing drug resistance. Apopto-
sis is a crucial cellular process and improper regulation of
apoptotic signaling pathways may lead to cancer formation.
Subsequently, the synthesis of efective chemotherapeutic
agents that can induce apoptosis in tumor cell has emerged
as a signifcant approach in cancer drug discovery.
Methods The goal of this work is to develop a potential
antitumor agent exerting signifcant inhibitory efects on
cancer cell and low cytotoxicity, for which we focused on
the structural features of 1,3,4-oxadiazoles as it a privileged
scafold in modern medicinal chemistry and have the ability
to inhibit growth factors, enzymes and kinases potentially
Electronic supplementary material The online version
of this article (doi:10.1007/s00280-017-3414-6) contains
supplementary material, which is available to authorized users.
* Abdul Roouf Bhat
abroouf@gmail.com
* Fareeda Athar
fathar@jmi.ac.in
1
Centre for Interdisciplinary Research in Basic Sciences,
Jamia Millia Islamia, New Delhi 110025, India
2
National Institute of Immunology, New Delhi 110067, India
3
Department of Chemistry, Sri Pratap College, Cluster
University, Srinagar 190001, India
4
Department of Chemistry, Jamia Millia Islamia,
New Delhi 110025, India