Convenient one-pot synthesis of chromone derivatives and their antifungal and antibacterial evaluation

Article abstract of DOI:10.1080/00397911.2011.647222

A one-pot method for the synthesis of chromone derivatives from the reaction of 2-hydroxyacetophenones with aliphatic or aromatic acid chlorides is reported. Esterification and Baker-Venkataraman rearrangement were promoted by t-BuOK, which was followed directly by acid-catalyzed cyclization in one pot. Some of 2-cyclohexyl- and 2-cyclohexylmethyl-substituted chromones displayed activity against plant pathogenic fungal strains. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.647222

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Convenient One-Pot Synthesis of
Chromone Derivatives and Their
Antifungal and Antibacterial Evaluation
Sherif B. Abdel Ghani a , Patrick J. Mugisha b , Juliet C. Wilcox b
,
Emad A. M. Gado a c , Erere O. Medu d , Andrew J. Lamb d & Richard
C. D. Brown b
a Faculty of Agriculture, Ain Shams University, Hadayek Shoubra,
Cairo, Egypt
b School of Chemistry, University of Southampton, Highfield,
Southampton, United Kingdom
c Department of Biological Sciences, Faculty of Science, Taif
University, Taif, Saudi Arabia
d School of Pharmacy and Life Sciences, Robert Gordon University,
Aberdeen, United Kingdom
Accepted author version posted online: 05 Jun 2012.Version of
record first published: 06 Mar 2013.
To cite this article: Sherif B. Abdel Ghani , Patrick J. Mugisha , Juliet C. Wilcox , Emad A. M. Gado ,
Erere O. Medu , Andrew J. Lamb & Richard C. D. Brown (2013): Convenient One-Pot Synthesis of
Chromone Derivatives and Their Antifungal and Antibacterial Evaluation, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:11, 1549-1556
To link to this article: http://dx.doi.org/10.1080/00397911.2011.647222
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Synthetic Communications1, 43: 1549–1556, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.647222
CONVENIENT ONE-POT SYNTHESIS OF CHROMONE
DERIVATIVES AND THEIR ANTIFUNGAL AND
ANTIBACTERIAL EVALUATION
Sherif B. Abdel Ghani,1 Patrick J. Mugisha,2 Juliet C. Wilcox,2
Emad A. M. Gado,1,3 Erere O. Medu,4 Andrew J. Lamb,4 and
Richard C. D. Brown2
1Faculty of Agriculture, Ain Shams University, Hadayek Shoubra, Cairo,
Egypt
2School of Chemistry, University of Southampton, Highfield, Southampton,
United Kingdom
3Department of Biological Sciences, Faculty of Science, Taif University,
Taif, Saudi Arabia
4School of Pharmacy and Life Sciences, Robert Gordon University,
Aberdeen, United Kingdom
GRAPHICAL ABSTRACT
Abstract A one-pot method for the synthesis of chromone derivatives from the reaction of
2-hydroxyacetophenones with aliphatic or aromatic acid chlorides is reported. Esterifica-
tion and Baker–Venkataraman rearrangement were promoted by t-BuOK, which was
followed directly by acid-catalyzed cyclization in one pot. Some of 2-cyclohexyl- and
2-cyclohexylmethyl-substituted chromones displayed activity against plant pathogenic
fungal strains.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Antifungal activity; chromones; flavonoids; heterocycles
Received November 22, 2011.
Address correspondence to Sherif B. Abdel Ghani, Faculty of Agriculture, Ain Shams University,
Hadayek Shoubra 11241, Cairo, Egypt. E-mail: sherifbiomy@yahoo.com; or Richard C. D. Brown,
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK. E-mail:
rcb1@soton.ac.uk
1549

1550
S. B. A. GHANI ET AL.
INTRODUCTION
The application of synthetic pesticides has undoubtedly played a vital role in deli-
vering enhanced yields of crops and securing food supplies in developed countries. How-
ever, there has been concern for many years regarding the persistence of pesticides in the
environment and their effect on human health and ecosystems,[1] leading to restrictions
in the use of synthetic pesticides.[2] In addition, increasing resistance has challenged the
efficacy of some available pesticides, fueling the search for new classes of active com-
pounds.[3–5] Natural products have proved to be a source of many compounds applied
in crop protection,[6,7] and their derivatives are likely to deliver additional novel leads in
the future. Flavonoids are widely distributed compounds in plants and are some of the
most studied natural products.[8] A variety of bioactivities has been reported for flavo-
noid derivatives including antifungal,[9,10] antibacterial,[9,11–14] and insecticidal[15–18]
activity. In a previous article, we described the synthesis of some flavones and chro-
mones and their preliminary antibacterial and antifungal evaluation.[9] Of the com-
pounds tested, we found those where the ring B in the flavone was replaced with
a cyclohexyl group gave enhanced activity against Gram-positive bacteria as well as
promising results against Aspergillus niger. In this article, we describe the synthesis of
chromone derivatives using a convenient one-pot procedure and the evaluation of
selected compounds for antifungal and antibacterial activities.
RESULTS AND DISCUSSION
To facilitate our studies of the antifungal and antibacterial potential of
chromone derivatives, we required an effective synthesis of the chromone core that
would deliver the compounds for testing as well as chromone intermediates suitable
for further diversification. In an earlier work, we employed a modification of the
well-known Baker–Venkataraman rearrangement reported by Riva et al. using
pyridine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to synthesize chromone
derivatives.[19] Overall, the process was performed in two steps, with the isolation
and purification of the b-diketone followed by an acid-catalyzed dehydrative
cyclization that was conducted under microwave irradiation.[9] Although this proto-
col worked well, we wished to develop a one-pot preparation while minimizing the
use of toxic and costly reagents. Ares et al. had shown potassium tert-butoxide to
be effective for both acylation and subsequent acyl transfer (Baker–Venkataraman)
reactions,[20] although cyclization of the diketone was performed as a separate
step. Herein we describe the application of a simple synthesis of chromones using
potassium tert-butoxide followed by acid treatment and cyclization in one pot. We
also report antifungal and antibacterial activity data for selected products.
Treatment of 2-hydroxy-5-bromoacetophenone (1a) and cyclohexanecarboxylic
acid (2a) with 2 equivalents of t-BuOK in tetrahydrofuran (THF) at ambient tempera-
ture resulted in rapid and clean conversion to the ester 3aa (Scheme 1). Alternatively,
the reaction mixture was heated under reflux for 1 h and rearrangement of the
intermediate ester to the b-diketone 4aa was observed. The b-ketoester was obtained
as a mixture of isomers including the enol tautomers. Analysis of the reaction mixture
indicated the presence of several compounds including structural isomers of 4aa and
some 2-hydroxyacetophenone due to cleavage of the intermediate ester. Nonetheless,

ONE-POT SYNTHESIS OF CHROMONE DERIVATIVES
1551
Scheme 1. One-pot synthesis of chromones.
cyclization of the crude reaction mixture was conveniently achieved by acidification of
the crude mixture with H2SO4 (final concentration of 2.3 M) and heating under reflux
to give the chromone 5aa. Following column chromatography, chromone 5aa was
isolated in 44% overall yield from the 2-hydroxyacetophenone 1a.
Under the relatively strongly acidic conditions employed for the cyclization,
by-products originating from acid-catalyzed ring-opening reactions of the reaction
solvent THF were observed. In some cases, these were difficult to remove by column
chromatography. Replacing the solvent with 1,4-dioxane led to inferior yields of
chromones. However, simply reducing the amount of H2SO4 (final solution concen-
tration of 0.2 M in THF) used in the cyclization step reduced the side reaction,
providing an enhanced yield of 5aa (58%, entry 1, Table 1). The one-pot synthetic
protocol was then applied to a variety of chromone derivatives 5aa–5ec, in satis-
factory to good yields (Table 1). A series of flavones (2-arylchromones) 5ad–5eg
were also synthesized in 46–75% yields using the one-pot protocol (Table 2).
Selected synthetic chromones were tested against Drechselera oryzae, Alternaria
alternate, Fusarium oxysporium, Aspergillus niger, and Macrophomina phaseolina
(Table 3).[21] Most of the tested compounds showed significant growth inhibition of
the tested fungal species, with the exception of the 7-fluorochromones, which showed
no inhibition at concentrations up to 42 mg=cm2. The previously reported cyclohexyl-
derivatives 5ac and 5bc (entries 4 and 5) were tested concurrently with the newly
synthesized analogs for comparison.
Drechselera oryzae was the most sensitive fungus among the tested fungi, with
compounds 5ac, 5bc, and 5bf displaying the most effective inhibition with IC50 values
of 0.007, 0.002, and 0.009 mg=cm2 respectively (entries 4, 5, and 7). Compounds 5ba
and 5da were the most potent inhibitors against Alternaria alternata, with IC50 values
of 2.27 and 2.67 mg=cm2 respectively (entries 2 and 3). In the case of Fusarium and
Aspergillus the similar inhibitory potency was observed for most of the tested com-
pounds with IC50 values in the range 2.20–3.12 mg=cm2 (entries 1–7), with the excep-
tion of compounds 5da and 5bf, which showed reduced potency toward Aspergillus
(IC50 values 8.7 and 37.39 mg=cm2 respectively). For the fungus Macrophomina,
broadly similar activity of the compounds in entries 1–7 was observed.
Following from the antifungal investigation, a small number of chromones were
used to screen for antibacterial activity.[22] When examined against a methicillin-sensitive

1552
S. B. A. GHANI ET AL.
Table 1. One-pot synthesis of chromones
Reactants
Entry
1
2
Product
R1
R2
Yield (%)a
1
2
3
4
5
6
1a
1b
1c
1d
1a
1b
2a
5aa
5ba
5ca
5da
5ab
5bb
6-Br
58
57
34
35
48
41
2a
2a
2a
2b
2b
6-OMe
6-OH
7-OMe
6-Br
6-OMe
7
8
1a
1b
1d
1e
2c
2c
2c
2c
5ac
5bc
5dc
5ec
6-Br
62
72
54
54
6-OMe
7-OMe
7-F
9
10
aIndicates isolated yield of analytically pure material.
strain of the Gram-positive organism Staphylococcus aureus (MSSA), 5ba was
observed to have a moderate minimum inhibitory concentration (MIC) of 64 mg=
mL. The only other compound with any notable activity was 5aa, which yielded an
MIC of 97.5 mg=mL against MSSA. Clearly, this antibacterial activity is somewhat
strain-specific, as only 5ba had any activity against a methicillin-resistant strain of this
organism. When screened against the Gram-negative organism Escherichia coli, 5ba
was found to display only very weak activity. A stronger antibacterial action of
5ba against Gram-positive organisms would suggest that the lipopolysaccharide
(LPS) layer surrounding E. coli prevents access of the compound into the cell
and in so doing limits activity. Lacking an LPS layer, Gram-positive cells with just
a peptidoglycan cell wall may be more easily accessed by the chromones.
In summary, a simple and effective one-pot synthesis of chromones is described,
which has been used to prepare a number of derivatives bearing cycloakyl and aryl
substituents at the 2-position. This approach avoids the use of toxic and expensive
amine bases such as pyridine and DBU. Preliminary investigations show some of these
chromones to possess activity against plant pathogenic fungi and one compound, 5ba,
displayed activity against a methicillin-resistant strain of Staphylococcus aureus.
EXPERIMENTAL
All reactions were carried out under an inert atmosphere of N2 gas in oven-
or flame-dried glassware. The solvents CH2Cl2 (from CaH2) and tetrahydrofuran
(THF) (from Na=benzophenone) were distilled prior to use. All other solvents

ONE-POT SYNTHESIS OF CHROMONE DERIVATIVES
1553
Table 2. One-pot synthesis of flavones
Reactants
Entry
1
2
Product
R1
Ar
Yield (%)a
1
2
3
4
5
6
7
1a
1b
1d
1e
1a
1b
1d
2d
5ad
5bd
5dd
5ed
5ae
5be
5de
6-Br
46
62
54
60
49
75
52
2d
2d
2d
2e
2e
2e
6-OMe
7-OMe
7-F
6-Br
6-OMe
7-OMe
8
9
1a
1b
1d
2f
2f
2f
5af
5bf
5df
6-Br
6-OMe
7-OMe
51 (68)b
67
49
10
11
12
1b
1e
2g
2g
5bg
5eg
6-OMe
7-F
61
56
aIndicates isolated yield of analytically pure material.
bIsolated yield obtained under modified conditions for the cyclisation step (0.2 M H2SO4).
and reagents were used as received. Thin-layer chromatography (TLC) was
performed on aluminium-precoated plates of silica gel 60, and chromatograms
were visualized under ultraviolet (UV) light and=or by staining with potassium
permanganate solution. Flash chromatography was performed using 35 to 70-mm
Table 3. IC50 dataa for chromone derivativesb 5aa, 5ba, 5da, 5ac, 5bc, 5af, and 5bf
Drechselera
oryzae
Alternaria
alternate
Fusarium
oxysporium
Aspergillus
niger
Macrophomena
spp.
Entry Compound
1
2
3
4
5
6
7
5aa
5ba
5da
5ac
5bc
5af
5bf
0.145 ꢀ 0.047 3.450 ꢀ 0.209 2.992 ꢀ 0.145
1.753 ꢀ 0.058 2.275 ꢀ 0.254 2.812 ꢀ 0.065
0.397 ꢀ 0.036 2.679 ꢀ 0.147 2.603 ꢀ 0.147
2.815 ꢀ 0.112
3.118 ꢀ 0.036
8.736 ꢀ 0.77
2.81 ꢀ 0.17
3.889 ꢀ 0.167
5.051 ꢀ 0.157
3.967 ꢀ 0.532
4.67 ꢀ 0.48
0.007 ꢀ 0.006
0.002 ꢀ 0.007
4.89 ꢀ 0.71
4.69 ꢀ 1.28
2.26 ꢀ 0.088
2.20 ꢀ 0.066
2.59 ꢀ 0.88
3.79 ꢀ 3.60
0.186 ꢀ 0.031 2.842 ꢀ 0.049 2.455 ꢀ 0.073
2.778 ꢀ 0.76
3.023 ꢀ 0.35
4.362 ꢀ 0.443
0.009 ꢀ 0.009 4.488 ꢀ 0.142 3.052 ꢀ 0.363 37.392 ꢀ 3.424
aIC50 values are reported in mg=cm2.
bCompounds 5ec, 5ef, and 5eg did not display activity in the assays up to 42 mg=cm2.

1554
S. B. A. GHANI ET AL.
silica gel. 1H spectra were recorded at 300 MHz while 13C NMR spectra were
recorded at 75MHz or 100 MHz, in CDCl3 (unless otherwise stated) with CHCl3
1
(d ¼ 7.27ppm H, d ¼ 77.0 ppm 13C) as the internal standard. Infrared (IR) spectra
were obtained using the neat compounds and are reported in wave numbers (cmꢁ1).
Melting points were obtained in open-ended capillary tubes and are uncorrected. All
electrospray positive (ESþ) low-resolution mass spectra (LRMS) were recorded on
a Waters ZMD quadrupole spectrometer. High-resolution electrospray positive (ESþ)
was performed on a FT-ICR Bruker Apex III spectrometer. Physical and spectroscopic
data for known compounds were consistent with reported values: 5ac,[9] 5bc,[9] 5dc,[23]
5ad,[9] 5bd,[18] 5dd,[18] 5ae,[9] 5de,[20] 5df,[24] and 5bg.[9] Compound 5ed has also been
reported previously,[25] although our data are not consistent with the partial data
reported. Our full characterization data for 5ed are therefore provided herein.
Procedure for the Synthesis of Chromones: 6-Bromo-2-
(cyclohexylmethyl)-4H-chromen-4-one (5aa)
Cyclohexylacetyl chloride (2a, 0.657 mL, 4.20 mmol) was added dropwise to
a stirred solution of 5-bromo-2-hydroxy-acetophenone (1a, 900 mg, 4.20 mmol)
and t-BuOK (988 mg, 8.80 mmol) in THF (50 mL), and then the mixture was heated
at 80 ꢂC for 5 h to afford the crude b-diketone. The reaction mixture was allowed to
cool to rt, concentrated H2SO4 (7.5 mL, 135 mmol) was added dropwise, and the
mixture was heated at 90 ꢂC for 3 h. The mixture was cooled to rt, diluted with
EtOAc, and then poured into aqueous 2 N NaOH (60 mL). The organic layer was
separated, re-extracting the aqueous solution with EtOAc. The combined organic
extract was washed sequentially with aqueous HCl (5%), NaHCO3 (5%), and brine
and then dried (MgSO4). Solvent was removed under reduced pressure to afford
a brown-orange oil (2.50 g). Purification by column chromatography (SiO2) eluting
with EtOAc=hexane (2.5:97.5 ! 20:80) afforded the title compound 5aa (780 mg,
2.41 mmol, 58%) as a pale orange solid.
Modified Procedure for the Synthesis of Chromones: 6-Bromo-2-
(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (5af)
4-Trifluoromethylbenzoyl chloride (2f, 600 mL, 4.0 mmol) was added dropwise
to a stirred solution of 5-bromo-2-hydroxy-acetophenone (1a, 860 mg, 4.0 mmol) and
t-BuOK (942 mg, 8.4 mmol) in THF (50 mL). The mixture was heated at 80 ꢂC for 3 h
to afford the crude b-diketone. The reaction mixture was allowed to cool to rt, con-
centrated H2SO4(0.5 mL, 9.0 mmol) was added, and the mixture was heated at 90 ꢂC
for 2 h. The mixture was diluted with EtOAc (50 mL), washed sequentially with
aqueous NaHCO3 (5%) and brine, and dried (MgSO4). The solvent was removed
under reduced pressure to afford an orange solid. Purification by column chromato-
graphy eluting with EtOAc=hexane (5:95 ! 30:70) afforded the title compound 5af
(1.01 g, 2.74 mmol, 68%) as an orange-yellow solid.
6-Bromo-2-(Cyclohexylmethyl)-4H-chromen-4-one (5aa).ꢁY1 ield 58%;
pale orange solid; mp 99–101 ꢂC; IR (neat) nmax 1651 (C O) cm
;
1H NMR
=
(300 MHz, CDCl3) d 8.31 (1H, d, J ¼ 2.4 Hz, Ar-H5), 7.72 (1H, dd, J ¼ 9.0,

ONE-POT SYNTHESIS OF CHROMONE DERIVATIVES
1555
2.4 Hz, Ar-H7), 7.33 (1H, d, J ¼ 9.0 Hz, Ar-H8), 6.16 (1H, s), 2.49 (2H, d, J ¼ 7.0 Hz,
CH2), 1.90–1.66 (6H,m), 1.36–1.05 (5H, m) ppm; 13C NMR (75 MHz, CDCl3) d
176.6 (C), 168.8 (C), 155.1 (C), 136.1 (CH), 128.1 (CH), 124.9 (C), 119.7 (CH),
118.1 (C), 110.7 (CH), 42.0 (CH2), 36.1 (CH2), 32.8 (CH), 25.9 (CH2), 25.8 (CH2)
ppm; LRMS (ESþ) m=z 321.1 (& 323.1) [M þ H]þ. HRMS (ESþ) m=z C16H18BrO2
requires 321.0485; found 321.0491.
6-Bromo-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (5af). Yield
51%; orange-yellow solid; mp 174–176 ꢂC; IR (neat) nmax 1659 (C O) cmꢁ1; H
1
=
NMR (300 MHz, CDCl3) d 8.37 (1H, d, J ¼ 2.6 Hz, Ar-H5), 8.04 (2H, d, J ¼ 8.9 Hz),
7.82 (1H, dd, J ¼ 8.9, 2.6 Hz, Ar-H7), 7.81 (2H, d, J ¼ 8.9 Hz), 7.50 (1H, d,
J ¼ 8.9 Hz, Ar-H8), 6.88 (1H, s, H3) ppm; 13C NMR (100 MHz, CDCl3) d 176.7
(C), 161.9 (C), 154.9 (C), 137.0 (CH), 134.8 (C), 133.4 (q, JCF ¼ 33 Hz), 128.5
(CH), 126.7 (CH), 126.1 (2 C, q, JCF ¼ 4 Hz, CH), 125.2 (C), 124.9 (JCF ¼ 271 Hz,
C), 120.0 (CH), 119.0 (C), 108.7 (CH) ppm; LRMS (ESþ) m=z 761.1 (& 763.2)
[2M þ Na]þ. HRMS (ESþ) m=z C32 H16 Br2F6O4Na requires 760.9212; Found
760.9164.
ACKNOWLEDGMENT
This work was partially supported by the Egyptian Ministry of Higher
Education and State for Scientific Research (MHESR) under the ParOwn programe.
REFERENCES
1. Gavrilescu, M. Eng. Life Sci. 2005, 5, 497–526.
2. House Resolution 1627. Food Quality Protection Act (FQPA) of 1996. Available at
http://www.epa.gov/pesticides/regulating/laws/fqpa/.
3. Orhan, D. D.; Ozcelik, B.; Ozgen, S.; Ergun, F. Microbiol. Res. 2010, 165, 496–504.
4. Thines, E.; Anke, H.; Weber, R. W. S. Mycol. Res. 2004, 108, 14–25.
5. Sultatos, L. G. J. Toxicol. Env. Health 1994, 43, 271–289.
6. (a) Copping, L. G.; Duke, S. O. Pest Manag. Sci. 2007, 63, 524–554; (b) Copping, L. G.;
Khambay, B. P. S. Pest Manag. Sci. 2000, 56, 649–650.
7. Dayan, F. E.; Cantrell, C. L.; Duke, S. O. Bioorg. Med. Chem. 2009, 17, 4022–4034.
8. Bohm, B. A. Introduction to Flavonoids; Harwood Academic Publishers: London, 1998.
9. Brown, R. C. D.; Ghani, S. B. A.; Weaver, L.; Zidan, Z. H.; Ali, H. M.; Keevil, C. W.
Bioorg. Med. Chem. Lett. 2008, 18, 518–522.
10. O’Neill, T. M.; Mansfield, J. W. Trans. Br. Mycol. Soc. 1982, 79, 229–237.
11. Mori, A.; Nishino, C.; Enoki, N.; Tawata, S. Phytochem. 1987, 26, 2231–2234.
12. Goker, H.; Boykin, D. W.; Yildiz, S. Bioorg. Med. Chem. 2005, 13, 1707–1714.
13. Basile, A.; Giordano, S.; Lopez-Saez, J. A.; Cobianchi, R. C. Phytochem. 1999, 52,
1479–1482.
14. Lamb, A. J.; Cushnie, T. P. T.; Hamilton, V. E. S. Microbiol. Res. 2003, 158, 281–289.
15. Isman, M. B.; Rodriguez, E. Phytochem. 1983, 22, 2709–2713.
16. Upasani, S. M.; Kotkar, H. M.; Mendki, P. S.; Maheshwari, V. L. Pest Manag. Sci. 2003,
59, 1349–1354.
17. Rao, K. V.; Chattopadhyay, S. K.; Reddy, G. C. J. Agric. Food Chem. 1990, 38,
1427–1430.

1556
S. B. A. GHANI ET AL.
18. Morimoto, M.; Tanimoto, K.; Nakano, S.; Ozaki, T.; Nakano, A.; Komai, K. J. Agric.
Food Chem. 2003, 51, 389–393.
19. Riva, C.; DeToma, C.; Donadel, L.; Boi, C.; Pennini, R.; Motta, G.; Leonardi, A. Syn-
thesis 1997, 195–201.
20. Ares, J. J.; Outt, P. E.; Kakodkar, S. V.; Buss, R. C.; Geiger, J. C. J. Org. Chem. 1993, 58,
7903–7905.
21. Kofujita, H.; Ota, M.; Takahashi, K.; Kawai, Y.; Hayashi, Y. Phytochem. 2002, 61,
895–898.
22. Cushnie, T. P. T.; Lamb, A. J. Int. J. Antimicrob. Agents 2005, 26, 343–356.
23. Rao, D. M.; Rao, A. V. S. Ind. J. Chem. Sect. B 1992, 31, 335–337.
24. Ismail, K. A.; Abd El Aziem, T. Eur. J. Med. Chem. 2001, 36, 243–253.
25. Fioravanti, R.; Chimenti, F.; Bolasco, A.; Chimenti, P.; Secci, D.; Rossi, F.; Yanez, M.;
Orallo, F.; Ortuso, F.; Alcaro, S.; Cirilli, R.; Ferretti, R.; Sanna, M. L. Bioorg. Med.
Chem. 2010, 18, 1273–1279.