Med Chem Res
inflammatory and antioxidant activities. Arzneimittel-Forschung
54:530–537
rule of five. In the case of cinnamaldehyde derivatives
(Compounds C1, C2, and C3), the predicted CNS activity
was in agreeable range −1, 0, and 1 respectively (refer
Supplementary Table S1). Similarly, CNS activities of
vanillin azomethines were −2, 0, and 0 for V1, V2, and V3,
respectively. Therefore, it is clear that these two classes of
compounds can be utilized as a good series to inhibit
Aetylcholinesterase. The possible docked binding mode of
the azomethine derivatives reveal that the combination of
both electron withdrawing group and hydrophobic moieties
at the terminal end of the azomethine derivatives is
responsible for the activity, which in-turn reflects in the
activity profile as revealed in our study. Hence, these azo-
methine derivatives could be proposed as a potent class of
compounds for the AD.
Gwaram NS, Ali HM, Abdulla MA, Buckle MJ, Sukumaran SD,
Chung LY, Othman R, Alhadi AA, Yehye WA, Hadi AH, Has-
sandarvish P, Khaledi H, Abdelwahab SI (2012) Synthesis,
characterization, X-ray crystallography, acetylcholinesterase
inhibition and antioxidant activities of some novel ketone deri-
vatives of gallic hydrazide-derived Schiff bases. Molecules
17:2408–2427
Hameed A, Al-Rashida M, Uroos M, Abid Ali S, Khan KM (2017)
Schiff bases in medicinal chemistry:
a
patent review
(2010–2015). Expert Opin Ther Pat 27:63–79
Iqbal J, Saeed A, Shah SJ, al-Rashida M, Shams-ul M (2016) Biolo-
gical evaluation of azomethine–dihydroquinazolinone conjugates
as cancer and cholinesterase inhibitors. Med Chem 12:74–82
Jawale A, Datusalia AK, Bishnoi M, Sharma SS (2016) Reversal of
diabetes-induced behavioral and neurochemical deficits by cin-
namaldehyde. Phytomedicine 23:923–930
Kaupp G (2009) Mechanochemistry: the varied applications of
mechanical bond-breaking. Cryst Eng Comm 11:388–403
King AA, Shaughnessy DT, Mure K, Leszczynska J, Ward WO,
Umbach DM, Xu Z, Ducharme D, Taylor JA, Demarini DM,
Klein CB (2007) Antimutagenicity of cinnamaldehyde and
vanillin in human cells: global gene expression and possible role
of DNA damage and repair. Mutat Res 616:60–69
Kryger G, Silman I, Sussman JL (1999) Structure of acet-
ylcholinesterase complexed with E2020 (Aricept): implications
for the design of new anti-Alzheimer drugs. Structure 7:297–307
Kundu A, Mitra A (2013) Flavoring extracts of Hemidesmus indicus
roots and Vanilla planifolia pods exhibit in vitro acet-
ylcholinesterase inhibitory activities. Plant Foods Hum Nutr
68:247–253
Acknowledgements The authors are thankful to AIMST University,
Malaysia for providing laboratory facilities. These authors are indebted
to the Ministry of Higher Education (MOHE), Putrajaya, Malaysia for
funding the computational part (software and workstation) through the
Translational Research Grant Scheme (TRGS) 600-RMI/TRGS 5/3 (1/
2014) -3 to Universiti Teknologi MARA (UiTM).
Compliance with ethical standards
Conflict of interest The authors declare that they have no competing
interests.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experi-
mental and computational approaches to estimate solubility and
permeability in drug discovery and development settings. Adv
Drug Deliv Rev 46:3–26
Maestro Schrodinger Release 2015-1: version 10.1, Schrodinger, LLC,
New York (2015)
Molyneux P (2004) The use of the stable free radical diphenylpi-
crylhydrazyl (DPPH) for estimating antioxidant activity. Songk-
lanakarin J Sci Technol 26:211–219
Perumal P, Vasudevan M, Sridevi C, Manikandan S (2017) Antic-
holinesterase activity of octa peptides related to human histatin 8:
in-silico drug design and in-vitro. Asian J Pharm Clin Res
10:115–117
References
Augustyniak A, Bartosz G, Čipak A, Duburs G, Horáková L, Łuczaj
W, Majekova M, Odysseos AD, Rackova L, Skrzydlewska E,
Stefek M, Štrosová M, Tirzitis G, Venskutonis PR, Viskupicova
J, Vraka PS, Žarković N (2010) Natural and synthetic anti-
oxidants: an updated overview. Free Radic Res 44:1216–1262
Bendale AR, Bhatt R, Nagar A, Jadhav AG, Vidyasagar G (2011)
Schiff base synthesis by unconventional route: an innovative
green approach. Der Pharma Chemica 3:34–38
QikProp (2012) Rapid ADME. Schrödinger LLC, New York
Razik BM, Osman H, Ezzat MO, Basiri A, Salhin A, Kia Y, Mur-
ugaiyah V (2016) Efficient synthesis and discovery of schiff
bases as potent cholinesterase inhibitors. Med Chem 12:527–536
Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C
(1999) Antioxidant activity applying an improved ABTS radical
cation decolorization assay. Free Radic Biol Med 26:1231–1237
Salga SM, Ali HM, Abdullah MA, Abdelwahab SI, Wai LK, Buckle
MJ, Sukumaran SD, Hadi AH (2011) Synthesis, characterization,
acetylcholinesterase inhibition, molecular modeling and anti-
oxidant activities of some novel Schiff bases derived from 1-(2-
ketoiminoethyl) piperazines. Molecules 16:9316–9330
Santosh Kumar S, Priyadarsini KI, Sainis KB (2002) Free radical
scavenging activity of vanillin and o-vanillin using 1,1-diphenyl-
2-picrylhydrazyl (DPPH) radical. Redox Rep 7:35–40
Skoog DA, West DM, Holler FJ (1996) Fundamentals of analytical
chemistry. Saunders College Pub., New York
Chigurupati S, Selvaraj M, Mani V, Selvarajan KK, Mohammad JI,
Kaveti B, Bera H, Palanimuthu VR, Teh LK, Salleh MZ (2016)
Identification of novel acetylcholinesterase inhibitors: indolo-
pyrazoline derivatives and molecular docking studies. Bioorg
Chem 67:9–17
Ellman GL, Courtney KD, Andres Jr. V, Featherstone RM (1961) A
new and rapid colorimetric determination of acetylcholinesterase
activity. Biochem Pharmacol 7:88–95
Elseweidy MM, Askar ME, Elswefy SE, Shawky M (2017) Vanillin as
a new modulator candidate for renal injury induced by cisplatin in
experimental rats. Cytokine pii: S1043-4666(17):30225–30229
Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz
DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE,
Francis P, Shenkin PS (2004) Glide: a new approach for rapid,
accurate docking and scoring. 1. method and assessment of
docking accuracy. J Med Chem 47:1739–1749
Fugu M, Ndahi N, Paul B, Mustapha A (2013) Synthesis, character-
ization, and antimicrobial studies of some vanillin schiff base
metal (II) complexes. J Chem Pharm Res 5:22–28
Geronikaki A, Vicini P, Incerti M, Hadjipavlou-Litina D (2004)
Thiazolyl and isothiazolyl azomethine derivatives with anti-
Sridevi C (2015) Designing new vanillin schiff bases and their anti-
bacterial studies. J Med Bioeng 4:363–366
Sridevi C, Muralidharan S, Lim SC, Wei YR, Santhi K, Kesavanar-
ayanan KS (2017) Studying newly synthesized and developed 4-