1. Introduction
The steadily increasing microbial resistance to existing
irst drugs is a serious problem in antimicrobial cure
and necessitates continuing research into new classes
of antimicrobials [1]. Moreover, the progression of drug-
resistant strains has contributed to the ineficiency of
antimicrobial therapy. This has led to enormous interest
in antibacterial research, and we strongly believe that
there is an urgent call for development of new drugs
with diverse and unique structures and with novel
mechanisms of action from that of existing irst line
drugs. Consequently, this area of research is signiicant
and attracts much attention of an increasing number of
medicinal chemists.
Recently, we have been particularly interested
in the synthesis of N-arylpyrazole and 4H-chromene
incorporating structures for antimicrobial evaluation
[2] on the premise that N-arylpyrazole is a chemically
useful synthon bearing diverse biological activities like
antimicrobial [3-5], anti-inlammatory (COX-2 inhibitor
and ulcerogenic activity) [4], antitubercular [5], antitumor
[6,7], antiangiogenesis [7], anti-parasitic [8], antiviral
[9], analgesic and anxiolytic activity [10]. Moreover,
the 4H-pyrano[3,2-c]chromene nucleus is a fertile
source of biologically important molecules possessing
a wide spectrum of pharmacological activities, such
as antimicrobial [11], antiviral [12], mutagenicity [13],
antiproliferative [14], sex pheromone [15], antitumor [16],
cancer therapy [17] and central nervous system activity
[18].
Despite their importance from pharmacological and
synthetic point of views, comparatively few modiied
methods for the preparation of 4-aryl-4H-pyrano[3,2-c]
chromene derivatives [19] have been reported using
piperidine, morpholine, K
2
CO
3
, diammonium hydrogen
phosphate, H
6
[P
2
W
18
O
62
]•18H
2
O, tetrabutylammonium
bromide or water using various aromatic/heterocyclic
aldehydes, wherein not a single reference have been
found where 3-methyl-5-aryloxy-1-aryl-1H-pyrazole-
4-carbaldehyde is used. Thus, in view of the biological
signiicance of 4H-chromene, a modiication of the
4-position on 4H-pyrano[3,2-c]chromene by 3-methyl-
5-phenoxy-1-phenyl-1H-pyrazole is undertaken to
check whether it may bring signiicant changes in the
bioactivities of 4H-chromene derivatives. As a part of our
current studies in developing new antimicrobial agents
via combination of two therapeutically active moieties
Central European Journal of Chemistry
* E-mail: patelranjanben@yahoo.com
Department of Chemistry, Sardar Patel University,
Vallabh Vidyanagar-388120, Gujarat, India
Chetan B. Sangani, Divyesh C. Mungra, Manish P. Patel, Ranjan G. Patel
*
Synthesis and antimicrobial screening
of pyrano[3,2-c]chromene derivatives
of 1H-pyrazoles
Research Article
Abstract:
© Versita Sp. z o.o.
Received 20 January 2011; Accepted 10 March 2011
Keywords: Chromene • MCR • Pyrazole-4-carbaldehyde • Antimicrobial activity
A new series of twenty four derivatives of pyrano[3,2-c]chromene IVa-x bearing 1H-pyrazole were synthesized by a one pot,
base-catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde Ia-l, malononitrile II and 4-hydroxycoumarin IIIa-b.
All the synthesized compounds were characterized by elemental analysis, FT-IR,
1
H NMR and
13
C NMR spectral data.
All the synthesized compounds were screened against six bacterial pathogens, namely B. subtilis, C. tetani, S. pneumoniae, S. typhi,
V. cholerae, E. coli and for antifungal activity against two fungal pathogens, A. fumigatus and C. albicans using the broth microdilution
MIC method. Some of the compounds were found to be equipotent or more potent than commercial drugs against most of employed
strains, as evident from the screening data.
Cent. Eur. J. Chem. • 9(4) • 2011 • 635-647
DOI: 10.2478/s11532-011-0041-7
635