Synthesis of Some Chalcone and Their Heterocyclic Derivatives as Potential Antimicrobial Agents: A Review.

 

Arun Kumar¹, Vinita Gupta², Sanchita Singh², Y.K. Gupta^3*

¹Research Scholar, School of Applied Sciences Singhania University, Pacheri Bari, Jhunjhunu (Raj.), India

²Department of Chemistry, Agra College, Agra, U.P, India

³Head Department of Chemistry, B K Birla Institute of Engineering and Technology, Pilani, Rajasthan, India

*Corresponding Author E-mail: ykgbkbiet123@gmail.com

The Chalcone is aromatic compounds that forms the central core for different necessity of biological compounds, and are prepared by Claisen-Schmidt condensation of equimolar concentrations of arylaldehydes and acetophenones which are generally base catalysed. Chalcones are considered as the precursors of flavonoids and isoflavonoids. as the precursors the precursors of flavonoids and isoflavonoids. Chemically, chalcones are 1,3-diaryl-2-propen-1-ones in which two aromatic rings are joined by a three carbon bridge having a carbonyl moiety and α,β unsaturation. One of the most important classes of chalcones is the ring closure reactions with hydrazine, phenyl hydrazine, guanidine, urea etc. forming heterocyclic derivatives of chalcones. Both chalcones and their heterocyclic derivatives have a large number of pharmacological activities such as anti antimicrobial, antifungal, antibacterial, antioxidant, inflammatory, antitumor, anticancer, anti mitotic, anti leishmanial, anti-malarial, anti tubercular, antiviral, cytotoxic, etc. In this research paper (review) the efforts have been made to show some synthesis and biological activities of chalcones and their derivatives.

 

 

 

1. INTRODUCTION:

Chalcones are a major class which is belongs to the flavonoid family. They are considered as the precursors of flavonoids and is flavonoids. They are also the precursors of a number of biologically important heterocycles such as benzothiazepines, pyrazolines, and flavones. ^[1] They are generally distributed in tea, spices, soy based foods, fruits, vegetables and other plant products. Chemically, chalcones are 1,3-diaryl-2-propen-1-ones in which two aromatic rings or substituted aromatic rings are joined together by a three carbon atom α, β unsaturated carbonyl system. They have the following structure.

 

Figure 1 Structure of Chalcones

 

Generally, chalcones are prepared by Claisen-Schmidt condensation of aryl aldehydes and acetophenones. The reactions are catalyze based, but acid catalyzed, solid and resin supported, and microwave assisted versions are also reported. These reaction methodologies are related with draw backs such as long reaction times, low yields, use of expensive reagents and catalysts etc^{. [2]}

 

 

Figure 2 Synthesis of Chalcones

 

One of the essential class of reactions which chalcones undergo are the ring closure reactions with, malonitrile, hydrazine, guanidine  and so on bearing heterocyclic derivatives such as pyrimidine, pyrazoline, cyanopyridine, iso-oxazole   etc.^[3,4] The enone present in the chalcones provides an attractive site for 1,3-dinucleophiles affording such heterocyclicring-systems.^[5] Such reactions are generally catalysed by ethanolic NaOH or ethanolic KOH solutions under reflux conditions, however the utilization of different agents like piperidine is also reported.^[6]

 

Figure 3 Ring closure reactions of chalcones

 

Chalcones and their derivatives, whether naturally or synthetic occurring are an interesting and significant group of molecules as they have an extensive variety of pharmacological activities such as antimicrobial, antifungal, antibacterial, antioxidant, antitumor, anticancer, anti-inflammatory,  anti mitotic, anti leishmanial, anti-malarial, anti tubercular, antiviral, cytotoxic etc.^[7-20] Various chalcone and their derivatives are reported to inhibit various important enzymes of dissimilar cellular systems. Such enzymes incorporate aldose reductase, epoxide hydrolase, xanthine oxidase, protein tyrosine kinase, quinone reductase, monoamine oxidase and lipoxygenase. ^[21-23]

 

SYNTHESIS

Chemists are dealing with chalcones and their heterocyclic derivatives. A combined study was done on the synthesis of the compounds, where the researchers announced diverse synthetic pathways. These reports are presented below:

 Sivakumar PM et al reported the synthesis of α,β unsaturated ketones from substituted aromatic aldehydes and acetophenone.^[24]

 

Tomar V et al prepared a series of substituted chalcones by reacting 4’-piperazino acetophenone or 3-acetyl-2,5-dichlorothiophene and aromatic aldehyde.^[25]

 

Hans RH et al synthesized acetylenic chalcones from commercially available hydroxyacetophenone or benzaldehyde and commercially available vanillin or acetovanill one by O-alkylation followed by Claisen-Schmidt condensation. ^[26]

 

Bonesi M et al synthesized of a series of chalcones by aldolic condensations of 3,4,5- trimethoxy-acetophenone with appropriately substituted benzaldehydes.^[27]

 

The corresponding pyrazoles were synthesised by reacting each chalcone with methylhydrazine in tetrahydrofuran anhydrous at room temperature under argon.

 

Kumar D et al synthesized indolylchalcones by reacting indol-3-carboxaldehyde and appropriate acetophenone in presence of piperidine under reflux.^[28]

 

A second series of indolylchalcones were synthesized by reacting 3-acetylindole and appropriate aldehyde in presence of dilute sodium hydroxide under reflux.

 

Wanare G et al synthesized α-pyranochalcones from 3-acetyl-coumarin by condensation with substituted benzaldehydes by using a heterogeneous catalyst, silica sulfuric acid and novel solvent-free method.^[29]

 

Another pair of α-pyranochalcones were synthesized from 6-acetyl-5-hydroxy-4-methyl-2Hchromen- 2-one by condensation with substituted benzaldehydes using silica sulfuric acid as catalyst in solvent free conditions.

 

Mizuno CS et al synthesized retinoid-chalcone hybrids by coupling acetophenone with different aldehydes using NaOH in ethanol.^[30]

 

Siddiqui ZN et al synthesized heteroarylchalcones and their pyrazoline derivatives by reacting 5-chloro-3-methyl-1-phenyl pyrazole-4-carboxaldehyde and barbituric acid derivatives in both onventional and thermal solvent free conditions.^[31]

 

Solankee A et al synthesized chalcones by condensation of ketones with various aldehydes in presence of DMF and KOH. These chalcones were further reacted with hydrazine hydrate, guanidine nitrate, malononitrile to form acetylpyrazolines, aminopyrimidines and cyanopyridines respectively.^[32]

 

Champelovier P et al synthesized two chalcones (A and B) by reacting 2, 4,6-trimethoxy acetophenone and arylaldehydes in ethanol in presence of aqueous KOH.^[33]

 

Bandgar BP et al synthesized 3-(2,4-dimethoxy-phenyl)-1-phenyl-propenone by reacting substituted 1-phenyl ethanone and 2,4-dimethoxy-benzaldehyde or 3,4,5-  methoxybenzaldehyde

using NaOH as catalyst.^[34]

 

Budakoti A et al synthesized chalcones by Claisen-Schmidt condensation of acetophenone and substituted aromatic aldehydes in the presence of methanolic sodium hydroxide solution. Further derivatives were also synthesised.^[35]

 

Lavania A et al synthesised substituted chalcones by reacting 2-acetyl-5-chloro thiophene and aromatic aldehydes in the presence of sodium hydroxide, ethanol and PEG 400 acting as polymer support.^[36]

 

R=Anisaldehyde, 2-OH-5-BrBenzaldehyde,2-OHNaphthaldehyde,4-Nitro  Benzaldehyde 4-Cl Benzaldehyde,Piperonal,Furfural,4-Br Benzaldehyde

 

Zangade S et al synthesised some novel chalcones by grinding substituted 2-acetyl-1- naphthol and substituted benzaldehydes in presence of potassium hydroxide.^[37]

 

BIOLOGICAL ACTIVITIES

Chalcones and their heterocyclic derivatives were evaluated for several biological activities by various researchers. Here we are presenting a list of few biological activities reported by the researchers on chalcones and their heterocyclic derivatives.

 

Author	Synthesized Compounds	Activity Studied	Cell lines/Animal model/Organisms/ Enzymes
Sivakumar PM et al [24]		Antimycobacterial	M. tuberculosis (H37Rv)
Tomar V et al [25]		Anti-microbial	Staphylococcusaureus (209p),Escherichia coli (ESS 2231),Proteus vulgaris,Klebsiella pneumonia,Aspergillus fumigates,Candidaalbicans,Candida krusei(GO3),Candida glabrata(HO3)
Hans RH et al [26]		Anti-malarial, Anti-tubercular	P. falciparum (D10, W2 strains) M. tuberculosis (H37Rv strain)
Bonesi M et al [27]		ACE inhibitory activity	ACE preparation from rabbit lung (EC 3.4.15.1)
Kumar D et al [28]		Anti-tumor	Epithelial (A-549), Pancreatic carcinoma (PaCa-2), Androgen in dependent Human prostatic denocarcinoma (PC-3)
Wanare G et al [29]		Anti-malarial	Plasmodium falciparum(3D7), Plasmodium falciparum (RKL9), HeLa
Mizuno CS et al [30]		Anti-cancer	Colon cancer cell lines (HT-29)
Siddiqui ZN et al [31]		Anti-microbial	Streptococcus pyogenes (clinical isolate), Staphylococcus aureus (MRSA +Ve), Pseudomonas aeruginosa (ATCC-27853), Klebsiella Pneumoniae (clinical isolate), Escherichia coli (ATCC-25922), Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, Penicilliummarneffei
Solankee A et al [32]		Anti-microbial	Bacillus cereus, Micrococcus flavus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Salmonella typhimurium, Listeria monocytogenes
Champelovi er P et al [33]		Anti-cancer	Human glioblastoma glioma-derived cell lines U87, U118, U138, U373, T98G, GL26 and LN229
Bandgar BPet al [34]		Anti-cancer,Antiinflammatory, Anti-oxidant	ACHN (renal cell carcinoma),Pancc1 (pancreaticcarcinoma),Calu1 (non-smallcell lung arcinoma),H460 (non-small celllungcarcinoma),HCT116 (coloncarcinoma),THP-1 cells
Budakoti A et al [35]		Anti-amoebic	HM1:IMSS strain of E.histolytica
Dave SS et al [38]		Anti-bacterial, Anti-fungal	Escherichia coli,Pseudomonas vulgaris,Bacillus ubtilis,Staphylococcus aureus,Staphylococcus typhi,Candida albicans,Aspergillus niger,Pseudomonas chrysogenum.
Beyhan N etal[39]		Anticonvulsant	BALB/c mice
Rahaman SA et al [40]		Antihistaminic	Guinea pig (ilium)
Bandgar BP et al [41]		Antiinflammatory, Anti-bacterial, Anti-fungal	Bacillus subtilis (NCIM 2546), Escherichia coli (NCIM 2065), Staphylococcus aureus (NCIM 2120), Klebsiella pneumonia (NCIM5082), Proteus vulgaris (NCIM 2813), Aspergillus fumigatus (NCIM 902),spergillus niger(NCIM 545), Trichoderma viride (TT),Candida albicans (NCIM 3100),Penicilli- umchrysogenum (NCIM 707)
Sunduru N et al [42]		Antileishmanial	L.donovani(MHOM/IN/Dd8)
Rahaman SA et al [43]		Anti-microbial	Bacillus subtilis, Bacillus pumilis, Proteus vulgaris, Eschirichia coli
Mohammad F et al [44]		Anti-microbial	Bacillus pumilis, Bacillus subtilis, Escherichia coli, Proteus vulgaris, Aspergillus niger, Candida albicans
Ramalho SD et al [45]		Cytotoxic, Inhibition of Cathepsins K and B	MDA-MB-435, HCT-8,SF-295, Cathepsin B, Cathepsin K
Chimenti F et al [46]		MAOInhibitory	hMAO-A, hMAO-B

 

 

CONCLUSION:

From the above review it is evident that chalcones and their heterocyclic derivatives represent a promising class of compounds as they show a wide range of pharmacological activities, such as: anti-inflammatory, antimicrobial, antifungal, antibacterial, antioxidant, cytotoxic, antitumor, anticancer, antimitotic, antileishmanial, anti-malarial, antitubercular, antiviral etc. They also possess enzymes inhibitory activities including xanthine oxidase, aldose reductase, epoxide hydrolase, protein tyrosine kinase, quinone reductase, monoamine oxidase and lipoxygenase. A number of substitutions are possible in the aromatic rings and ring closure reactions of the chalcones affords heterocyclic derivatives which are pharmacologically active which further warrants the exploitation of this class of compounds.

 

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Received on 12.04.2017         Modified on 16.04.2017

Accepted on 26.04.2017         © AJRC All right reserved