INTRODUCTION:
Synthetic or natural chalcones are known to exhibit
various biological activities. They have been reported to possess
antibacterial,1 antifungal,2 anti-inflammatory,3
antitumor,4 and antioxidant activities.5, 6 The presence
of a reactive α, β-unsaturated keto function in chalcones is found to
be responsible for their antimicrobial activity, which may be altered depending
on the type and position of substituent on the aromatic rings. Chalcones are
also used as starting materials in the synthesis of many heterocyclic
compounds.7-10 In view of these observations and in continuation
work on the synthesis of bioactive heterocyclic compounds,11 it was
thought to synthesize some new series of chalcone derivatives.
EXPERIMENTAL:
All
the melting points were determined in an open capillary tube and are
uncorrected. Completion of the reaction was monitored by thin layer
chromatography on pre-coated sheets of silica gel-G. IR spectra were recorded
on FTIR-Shimadzu (in KBr cm-1) spectrometer. PMR spectra were
recorded in DMSO-d6 on Avanve-300 MHz spectrometer using TMS
as an internal standard. The mass were recorded on EI-Shimadzu-GC-MS
spectrometer.
General procedure for the synthesis of 2’-hydroxy-chalcone derivatives
(3a-f)
A
mixture of substituted acetophenone (0.01mol), aromatic carboxaldehyde
(0.01mol) and NaOH (0.02mol) were dissolved in methanol solution. The reaction
mixture was heated for 2-3 hr. The progress of the reaction was monitored by
TLC. After completion of the reaction the contents were poured in ice water and
then acidified by dil. HCl. The solid obtained was filtered, washed with cold
water. Then crude product was crystallized from ethanol to give the
corresponding product.
Spectral data of some selected compounds:
(3a): IR (KBr): 3133
(-OH), 1646 (>C=O), 1598 (C=C) cm-1; 1H NMR (DMSO-d6):
δ 6.89-8.62 (m, 9H, Ar-H + CH=CH), δ 12.51 (s, 1H, OH) ppm; M.S
(m/z): 260 (M+).
(3b): IR (KBr): 3088
(-OH), 1652 (>C=O), 1620 (C=C) cm-1; 1H NMR (DMSO-d6):
δ 7.31-8.65 (m, 8H, Ar-H + CH=CH), δ 13.22 (s, 1H, OH) ppm; M.S
(m/z): 291 (M+).
(3c): IR (KBr): 3067
(-OH), 1656 (>C=O), 1624 (C=C) cm-1; 1H NMR (DMSO-d6):
δ 7.28-8.68 (m, 8H, Ar-H + CH=CH), δ 13.45 (s, 1H, OH) ppm; M.S
(m/z): 386 (M+).
(3d): IR (KBr): 3152
(-OH), 1650 (>C=O), 1608 (C=C) cm-1; 1H NMR (DMSO-d6):
δ 7.35–7.55 (m, 8H, Ar-H + CH=CH), δ 12.38 (s, 1H, OH) ppm; M.S
(m/z): 247 (M+).
Antimicrobial activity:
The
antibacterial activity of the compounds was determined by agar diffusion method
against various bacteria like E. coli, S. typhi, S. aureus, B.
subtilis at various concentrations such as 20, 50 and 100 µg /ml. The zone
of inhibition was measured in mm and DMSO was used as solvent. Sterile nutrient
agar was seeded with test organism and layered in sterile petri plate.
After
solidification, agar cups were borered with cork borer 0.1 ml of the compound
solution was added to the cup with the help of micropipettes, one cup in the
plates was filled with solvent. Standard penicillin (10v/ml) was used as
reference drug.
The
plates were kept at low temperature (4 °C) for 20 minute to allow diffusion of
the compound. Then the plates were incubated at 37 °C for 24 hr. After proper
incubation the plates were observed for zone of no growth (zone of inhibition
of growth) around the cup.
Similarly
the same compounds were screened for the antifungal activity against different
organisms like P. chrysogenum, A. niger, F. moniliformae, and C.
albicans by using poison plate method. The compound was mixed with sterile
potato dextrose agar medium so as to get final concentration 2%. It was then
poured in sterile petri plate and allowed to solidify. Spots of test organisms
were placed on the agar surface. A plate without compound was prepared for
control. The plates were incubated at room temperature for 48 hr. After proper
incubation plates were observed for growth of the test organisms. The growth
indicates that the compound is not antifungal while inhibition of growth of
test organism indicates antifungal activity. The antifungal activities of the
compounds were compared with standard grysofulvin.
RESULTS
AND DISCUSSION:
In
this present paper, a series of various substituted chalcones were synthesized
by the condensation of substituted acetophenones with
pyridine-2-carbaldehyde/pyrrole-2-carbaldehyde in alkaline (NaOH) ethanolic
solution (Scheme-1 and Table-1).
The
products were confirmed by their spectral analysis. Appearance of IR bands at
3050-3160 (-OH) and 1645-1655cm-1 (>C=O) supported the structure.
1H NMR spectra, the multiplate around the δ 7.05-8.46 ppm
assigned to the aromatic protons. The phenolic proton appeared as singlet at
δ 12.20-13.50 ppm, while other aliphatic protons are appeared at excepted
regions. The mass spectra of the compounds showed corresponding molecular ion
peak which was correlated with their molecular weight of that respected compound.
The
results of antimicrobial data are given in Table-2. The data revealed that all
the compounds were found to be active against S. aureus and B. subtilis. Only
Compounds 3a and 3e were showed inhibition of growth against all the tested
fungi. Compound 3b showed reduced growth against one or more pathogens
CONCLUSION:
In
summary, we have synthesized some novel hetero chalcones having
pyridine/pyrrole moiety. All the synthesized compounds gave satisfactory
spectral and analytical data. The screening of antimicrobial data revealed that
the compounds 3a and 3e showed good antifungal activity. It was
also concluded that compounds with pyridine nucleus showed much active than
pyrrole.
ACKNOWLEDGEMENT:
The
authors are thankful to Principal, Yeshwant Mahavidyalaya, Nanded for providing
laboratory facilities and also to the Director, IICT, Hyderabad for providing
the instrumentation facilities.
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