Cancer Chemother Pharmacol
VIT University, India, for providing necessary laboratory facilities in
Chemistry and Biological evaluations. Authors also acknowledge Dr.
K. I. Sathiyanarayanan and B. Umamahesh, Department of Chemis-
try, VIT University, for their immense help in chemistry works.
the aromatic arene, azaarene, heteroarene, and phenol
ring were the substituent for PQPDs (4a–l) which were
played a major role in the anticancer activity. Since PI3
Kinases playing an important role in the cancer develop-
ment [34–36], PI3 Kinase enzyme inhibition assay was car-
ried out in support to understand the therapeutic abilities
of the PQPDs. 4a, 4b, and 4f were found as most potent
compounds in the activity (Fig. 1). PI3K-p110α is mostly
involved in the cancer development rather than other
subunits.
Funding No funding source available for this study. Sophisticated
Instrument Facility (SIF) from VIT University, Vellore-632014, India
is duly acknowledged for providing financial support and laboratory
facilities.
Compliance with ethical standards
A molecular docking study was also carried out in con-
nection with the PI3 Kinases enzyme inhibition assay stud-
ies. The least inhibitory constant derived in the molecu-
lar docking studies coincided the PI3 Kinase inhibition
assay. This indicates the association of functional groups
of PQPDs in the proposed activity. Compounds 4a and 4b
showed a most fortunate binding affinity values with low-
est ki (inhibitory constant) 53.33 and 41.23 pM. In the past
decades, quinoline scaffolds were analyzed for their anti-
cancer potent [37]. Structure–activity relationship (SAR)
studies were concerned in most of the reports to provide
strong support/evidence for contribution of small mole-
cules in the therapeutic activities. In the present study, SAR
studies revealed that few compounds among PQPDs (4a–l)
which were substituted with a different electron-withdraw-
ing and electron-releasing group at R2 position (C2) and at
R1 position (C16) of quinoline ring found as potent anti-
proliferative/anticancer agents. In fact, SAR studies dem-
onstrated the resemblance between the in silico and in vitro
evaluations as well as the correlation of functional group
contribution in the proposed activity.
Conflict of interest None.
Ethical approval No animal or human subjects were used in this
study. But all procedures performed in accordance with the ethical
standards of the institutional and/or national research committee or
comparable ethical standards.
References
1. Vikramdeep M, Amit N, Balasubramanian V, Prakash PB, Sarbjit
Singh J, Sukhraj K, Singh Prati Pal, Jain R (2004) Synthesis and
antimycobacterial activities of ring-substituted quinoline carbo-
hydrazide and ring-substituted quinoline carboxamide analogs.
Biorg Med Chem 12:6465–6472
2. Tseng CH, Chen YL, Lu PJ, Yang CN, Tzeng CC (2008) Syn-
thesis and antiproliferative evaluation of certain indeno[1,2-c]
quinoline derivatives. Bioorg Med Chem 16:3153–3162
3. Zhao YL, Chen YL, Chang FS, Tzeng CC (2005) Synthesis
and cytotoxic evaluation of certain 4-anilino-2-phenylquinoline
derivatives. Eur J Med Chem 40:792–797
4. Kuo SC, Lee HZ, Juang JP, Lin YT, Wu TS, Chang JJ, Lednicer
D, Paull KD, Lin CM, Hamel E, Lee KH (1993) Synthesis and
cytotoxicity of 1,6,7,8-substituted 2-(4′-substituted phenyl)-
4-quinolones and related compounds: identification as antimi-
totic agents interacting with tubulin. J Med Chem 36:1146–1156
5. Xia Y, Yang ZY, Xia P, Bastow KF, Tachibana Y, Kuo SC, Hamel
E, Hackl T, Lee KH (1998) Synthesis and biological evaluation
of 6,7,2′,3′,4′-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolo-
nes as a new class of antimitotic antitumor agents. J Med Chem
41:1155–1162
Conclusion
In conclusion, phenylquinoline phenol derivatives (PQPDs)
(4a–l) were successfully evaluated as PI3 Kinase inhibitors
so as the anticancer agents.
6. Firestone GL, Sundar SN (2009) Anticancer activities of arte-
misinin and its bioactive derivatives. Expert Rev Mol Med
11:e32
7. Lu JJ, Meng LH, Cai YJ, Chen Q, Tong LJ, Lin LP (2008)
Dihydroartemisinin induces apoptosis in HL-60 leukemia cells
dependent on iron and p38 mitogen-activated protein kinase acti-
vation but independent of reactive oxygen species. Cancer Biol
Ther 7:1017–1023
8. Kouznetsov VV, Rojas Ruíza FA, Vargas Méndeza LY, Gupta MP
(2012) Simple C-2-substituted quinolines and their anticancer
activity. Lett Drug Des Discov 9:680–686
9. Thigulla Y, Akula M, Trivedi P, Ghosh B, Jha M, Bhattacharya
A (2016) Synthesis and anticancer activity of 1,4-disubstituted
imidazo[4,5-c]quinolines. Org Biomol Chem 14:876–883
10. Mikata Y, Mika Y, Shun-ichiro O, Ichiro O, Kawasaki M, Maeda
M, Shigenobu Y (1998) Effect of side chain location in (2-ami-
noethyl)aminomethyl-2-phenylquinolines as antitumor agents.
Bioorg Med Chem Lett 8:1243–1248
• PQPDs 4a, 4b, 4f, 4g, and 4j were displayed potent PI3
Kinase enzyme inhibition activity conducted.
• Same compounds found with similar dominance in the
anticancer activity against MCF-7, a human breast can-
cer cell line.
• Binding mode and binding affinities in the docking
evaluations favoring the PQPDs (4a–l) equipped with –
CHO containing alkanol and ether groups.
• SAR study demonstrated a significant increase in
the potency of PQPDs (4a–l) that were substituted at
C2-position (R1) with different groups.
Acknowledgements The authors are grateful for the Sophisticated
Instrument Facility (SIF) and School of Bio-Science and Technology,
11. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing
activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59
1 3