Mata Gujri College of Pharmacy, Mata Gujri University, Purabpalli Road, Kishanganj, Bihar, 855107.
A simple structure found in naturally occurring compounds, chalcone has been utilised in medicinal chemistry to generate drugs that show promise in treating a range of illnesses. Here, we discuss the synthesis, properties, and structural diversity of chalcones. We next go over how chalcones are made and their biological properties, including their antibacterial, anti-inflammatory, anti-cancer, and antioxidant properties, highlighting the relationships between structure and activity. Chalcone derivatives continue to enthral medical scientists due to their straightforward synthesis, straightforward chemistry, ease of working with hydrogen atoms, and a number of intriguing biological functions. Chalcones have not yet gotten the recognition they merit despite their enormous potential as chemical feedstock for the creation and development of new, potent drugs.
Chalcones are naturally occurring substances in various plants, including vegetables, fruits, drinks, and more.1 Term "chalcone" derives from Greek word "chalcos," which translates to "bronze." referring to the colors found in most natural chalcones. 2 These include common in consumable plants and serve as precursors of flavonoids as well as isoflavonoids.3 Chalcones possess conjugated double bonds as well as a delocalized pi-electron system spanning both benzene rings. Molecules with this structure often have lower redox potentials and are more likely to conduct electron transfer processes. 4 Pure chalcones from several plants had licensed for medical studies to treat cancer and viral, and cardiovascular illnesses, demonstrating potential pharmacological action.5
Chemistry: -
Many chalcones found in nature have aryl rings that are polyhydroxylated. There are two isomeric forms of chalcones: cis and trans, with the transform being thermodynamically advantageous.6 However, as bioactivity is lost when this structural characteristic is removed, the common alpha-beta unsaturated ketone moiety is probably in charge of the many biological activities shown.7 Novel bioactive chalcone analogs compounds had created by altering both rings while leaving this moiety unaltered.8 Chalcones are often created via “Claisen-Schmidt condensation” of aldehyde as well as ketone, which can be catalyzed by acid or base and then dehydrated to produce chalcones.9
Synthesis: -
General Procedure:-
With stirring, 5 mmol of acetophenone and 5 mmol of benzaldehyde derivatives were dissolved in 10 ml of methanol. To produce a blood-red solution, quantities of potassium hydroxide (15 mmol) were added.10 For eight to twelve hours, resultant solution was swirled, causing chalcone to precipitate as potassium salt.11 After adding more concentrated HCl until solution became acidic, solution or suspension was poured into 10 milliliters of cold 1 N HCl.12 Product was obtained by filtering the resultant yellow solid, washing it with two 20 ml batches of water, and then recrystallizing it from appropriate solvent.13
Claisen-Schmidt condensation: -
The most popular and widely used method for creating chalcone is Claisen-Schmidt condensation, which condenses ketone and aldehyde with less work-up and fewer byproducts.14 Schmidt condensation is the most dominating method employing a diversity of catalysts such as lithium aluminum hydride, Potassium carbonate, and Pot. Hydroxide, Sodium Hydroxide, Aluminium Chloride, and Silica-Sulphuric acid.15 Here aldehyde and ketone react in presence of base in organic solvent and produce Chalcone with 60-80% yield.16
Microwave-assisted synthesis of chalcone:-17
Microwave-assisted synthesis is an efficient and eco-friendly method for preparing chalcones, which are important intermediates in medicinal and material chemistry.18,19 The reaction involves condensing an aromatic aldehyde with acetophenone in presence of a base catalyst like NaOH or KOH.20 Mix reactants with a base, optionally in ethanol or under solvent-free conditions.21 Irradiate mixture at 50–120°C for 2–10 minutes.[20] Cool, precipitate, and recrystallize product by using the ethanol.22, 23
Synthesis of chalcones using Schiff bases: -
Chalcones synthesis via Schiff bases is an alternative approach in organic synthesis, often leveraging the pre-formed Schiff base as a starting material or an intermediate.24 Schiff bases, Imine derivatives produced from condensation of primary amines with aldehydes or ketones, can react further to form chalcones under suitable conditions.25 it is a two-step process where an aromatic aldehyde with a primary amine forms a Schiff base.26 Schiff base undergoes a reaction with ketone in presence of a basic catalyst like NaOH and KOH, undergoing an aldol condensation to produce the chalcone.27
Recrystallization Process: -
Recrystallization is process where we isolate desired compound from a racemic mixture or mixed compound.28 Here we recrystallized chalcone derivative in various organic solvents based on their solubility.29, 30 Compounds 001 002 and 003 were recrystallized in methanol and compound 004 was recrystallized in ethanol and chloroform and compound 005 was recrystallized on methanol and Dichloromethane.31
Pharmacological Activities: -
Many antioxidants are produced by plants to protect molecules against reactive oxygen species, as well as main class of antioxidants obtained from plants is made up of phenolics.31,33 The flavonoids are arguably the most significant class of phenolic chemicals.34 They are capable of scavenging free radicals as well as to stop lipid peroxidation.35 The antioxidant potential is present in a large number of hydroxy chalcones with isoprenyl substituents on their phenyl rings.36 According to induction period measurements, chalcones, including 4-Chlorochalcone (001) and 2,4 Dichlorochalcone (002), are very potent antioxidants within concentration range of 0.025–0.1%.37
Anticancer Activity: -
Recent publications highlighting anti-proliferative as well as tumor-reducing properties of certain chalcones have heightened interest in this family of chemicals. Additionally, it has been established that substantial consumption of plant-based dietary flavonoids seems safe yet not linked to negative health effects.38,39 Chalcones represent a notable class of naturally occurring small molecules that were beneficial in cancer chemotherapy among currently recognized anticancer agents.40,41 According to sulforhodamine staining, 2,3-Dichlorochalcone might be useful as chemopreventive medication during prostate carcinogenesis, prostate hyperplasia, as well as decreased proliferation(IC50 between 26 & 12?M for 24,48, & 72 h).42 Studies on the toxicity of compounds to animals suggested that compound 002 might not be dangerous to people.43 Several chlorochalcones for their modes of action and anticancer properties. Compound 002 had strongest growth inhibitory efficacy of five chalcone derivatives examined, exhibiting IC50 values 1.5 & 0.6M in colony formation assay & (MTT) assay, correspondingly.44,45
Anti-inflammatory Activity: -
Inflammation constitutes multifaceted biological reaction to damaging factors that may result in various pathological conditions.46 Upon exposure to inflammatory triggers, macrophages produce pro-inflammatory substances, such as the transient free radical nitric oxide.47,48 Compound 001 was one of various chalcone derivatives evaluated for possible anti-inflammatory properties.49,50 It effectively scavenges superoxide anion created through activated human neutrophils or hypoxanthine/xanthine oxidase system(HX/XO), exhibiting IC50 values, 0.1 & 0.3M, correspondingly.51 Investigated the inhibitory effects of dimethyl amino-chalcones on creation of NO & PGE2 mediators within RAW 264.7 macrophage cells treated with lipopolysaccharide (LPS).52
Anti-bacterial Activity: -
Rapid resistance in Gram-positive bacteria presents a considerable safety risk.53 Methoxy-chalcone and chalcone exhibited strong antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, as well as Bacillus subtilis, exhibiting MIC values varying from 3.13 to 12.5 g/mL.54,55 Antibacterial action was seen on MRSA strains(OM481,OM505) exhibit MIC values 16~g/mL, while MRSA strains (K3& ST28) demonstrate MIC values 6.25~g/mL.56,57 The antibacterial activity of methoxy-chalcone analogs against S. aureus was found to be dependent on free hydroxyl group at 4-position in ring A. Elimination of lipophilic prenyl group leads to complete lack of activity.58
CONCLUSION: -
Present study shows that Chalcone derivatives have many Pharmacological activities that include anti-inflammatory, anti-cancer, antimicrobial, as well as antioxidant activities. This study also shows that synthesis of chalcone is done majorly via the Claisen-Schmidt condensation method. Chlorochalcone gives antioxidant activity while methoxy chalcone gives anti-bacterial activity. This study also shows that position of Chloro group in chalcone structure poses the anticancer activity. Moreover, significant actions, including anti-obesity, anti-hypertensive, as well as hepatoprotective effects, suggest that chalcone may serve as promising source of biologically active chemicals for these conditions.
REFERENCES
Saurabh Kumar Das, Jasvinder Singh, Naiyar Alam, Beauty Kumari, Sukanta Debnath*, Niharjyoti Saharia, The Role of Chalcones in Modern Medicinal Chemistry: A Review of Their Potential and Biological Activity, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 2289-2297. https://doi.org/10.5281/zenodo.14750375
10.5281/zenodo.14750375
