INTRODUCTION:

Chalcones are considered as one of the most versatile compounds due to its diverse distribution in nature with a vast array of biological activity. Naturally, chalcones are found plenty in plants¹ and are secondary plant metabolite². They fall under flavonoid family and serves as key precursors in the synthesis of many biologically active compounds such as pyrazolines, pyrimidines, aurones, benzalcoumaranones, aurones, flavones, flavanones etc^3,4. Chalcones manifest a bright yellow-colored compound⁵ and they can also be synthetically prepared in laboratory from commercially available chemical⁶. Two aromatic rings attached on opposite end with α, β-unsaturated carbonyl system constitute the general structure of chalcone. The aromatic ring in chalcone structure is completely delocalized system⁷. The conventional or most common reaction for preparing chalcone is Claisen-Schmidt condensation which are generally catalyzed by base but acid catalyzed are also employed sometimes⁸. Claisen-Schmidt condensation of chalcone is achieved by fusing acetophenone with benzaldehyde catalyzed by base ^{like NaOH, KOH,
Ba (OH)}₂^,

MgO and acid catalyst like HCl, BF3, B2O3, AlCl3 etc9. Chalcone possess a wide spectrum of biological activity with different compounds showing good activity against antifungal, anti-oxidant10-15, antimalarial16, anti-bacterial17,anti-inflammatory^18-20,antimicrobial activity^21-22,anti-diabetic activity²³,analgesic²⁴,anti-ulcerative, antiviral²⁵, Antileishmanial, antituberculosis²⁶,antipyretic, anti-hepatotoxic, antiallergic²⁷,antiparasitic, antileishmanial, antitubercular^28-29,antiplatelet, antitubercular, antihyperglycemic³⁰,immunosuppressive, antinociceptive properties³¹,anti-HIV, tyrosine kinase inhibitors³²,antiangiogenic³³,anti-spasmolytic activity, anti-invasive activity³⁴,effects on cancer cell growth³⁵, cytotoxic and anticancer activity^36-38.The diverse nature and vast spectrum of biological importance has prompted many researchers around the world to synthesized chalcone.

In recent years, the resistance of microbes to various antimicrobial drugs has raised major concerns over public health. Therefore, there is a urgent need to design and develop newer drugs with a wide spectrum of antimicrobial activity. Henceforth, we report the design and synthesis of a series of octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives (3a-e) and these compounds were investigated for their antimicrobial activity against two bacterial strains, gram positive Escherichia coli and gram-negative Staphylococcus aureus, and two fungal stains Penicillium italicum and Fusarium oxysporum.

MATERIALS AND METHODS:

All the reagents and solvents were purchased from commercially available sources and used without further purification. Melting points were recorded in open capillaries using IKON melting point apparatus and are uncorrected. FTIR spectra of the compounds were recorded on Perkin-Elmer spectrophotometer (Spectrum-Two) using KBr disk and values are expressed in cm^-1. ¹H-NMR and ¹³C-NMR spectra for the compounds were recorded using Bruker 300 MHz spectrophotometer in CDCl₃ as a solvent and TMS as an internal standard, values are given in parts per million (ppm). Mass spectra for the compounds were recorded on Advion Expression (S) CMS system. Progress of the reactions was monitored by Thin Layer Chromatography (TLC) with silica gel plates (Merck) using ethylacetate and n-hexane (3:7) as a solvent system and visualized under UV-light/iodine vapors.

General procedure for the synthesis of octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives (3a-3e):

To a mixture of octadecanoic acid (4-acetyl-phenyl)-amide 1 (0.401 g, 1 mmol), 4-chlorobenzaldehyde 2a (0.140 g, 1 mmol) in methanol (15 mL) was added NaOH (40%) and the reaction mixture was stirred under refluxing conditions for 24 h. The progress of the reaction was monitored by TLC. After completion of the reaction, crushed ice was added and filtered. The solid product was washed with water (3-4 times) to obtained the pure octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone (3a). The same method was followed for the synthesis of other compounds (3b-3e) (represented in Scheme-1).

Scheme 1. Synthesis of octadecanoic acid[4-(3-phenyl-acryloly)-phenyl]-amide chalcones (3a-e)

Antimicrobial activity:

The antimicrobial activity of the synthesized chalcone derivatives were evaluated against bacteria and fungi by agar well diffusion method^39-40.Escherichia coli and Staphylococcus aureus were used as test organisms for antibacterial study whereas, Penicillium italicum and Fusarium oxysporum were used as test organisms for antifungal study.

The bacterial strains were grown in nutrient broth media at 37℃±2℃ for 24 hours. An aliquot of 200µL of the freshly grown bacterial culture containing approximately 10⁵ – 10⁶ CFU/mL were spread over nutrient-agar plates. Wells were made on the agar plates using a sterilize cork borer and the test compounds were added into their respective marked wells. The compounds were tested in concentrations of 10µg/uL using dimethyl sulfoxide (DMSO) as solvent. Streptomycin was taken as the positive standard. The plates were incubated at 37℃ for 24hours. The antibacterial activity of the compounds was determined by measuring the diameter of inhibition zone.

All those compounds screened for antibacterial activity were also tested for their antifungal activity in Sabouraud dextrose agar medium by following the same well diffusion method against Penicillium italicum and Fusarium oxysporum. Fresh fungal cultures were grown in Sabouraud dextrose broth at 27℃±2℃ for around 48 hours. Around 200µL of the freshly grown cultures were seeded on Sabouraud agar plates. Wells were made on the agar plates and the test compounds at 10µg/µL concentration were added into the wells. The plates were incubated at 27℃ for 48 hours. The antifungal activity of the synthesized compounds was evaluated by measuring the diameter of the inhibition zone. The antifungal activity of the test compounds was compared with standard drug Fluconazole at the same concentration. All experiments were performed in triplicate to confirm reproducibility.

RESULTS AND DISCUSSIONS:

Chemistry:

In the present study, we report the synthesis of octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives under base-catalyzed Claisen-Schmidt condensation. The synthetic route begins with the reaction of octadecanoic acid (4-acetyl-phenyl)-amide 1 and substituted benzaldehyde 2a-2e in the presence of NaOH in methanol under reflux to yield the corresponding octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives 3a-3d (Scheme 1). The chalcone derivatives synthesized were reflux with constant stirring with most of the reaction completing within 24 hours depending upon the types of aldehyde used. The preliminary confirmation of the final product obtained was confirmed by thin layered chromatography with the formation of a single spot on the TLC plate. Figure 1 indicates that the halogen group in chalcone derivatives were highly reactive giving a good amount of solid product. This may be due to the electron withdrawing group which made it more electropositive which are likely bound to be attack by nucleophile. The base-catalyst NaOH used also enhances the reactivity of the reaction.

Figure 1. Synthesis of compound 3a-e

The reaction reported here is a one-step reaction using NaOH as catalyst along with 3 drops of water. Variation in the reaction mixture color and physical properties was observed with reaction initially after mixing the reactant shows pale yellow insoluble solid which upon further heating and stirring turns to dark yellow soluble solution. Generally, upon careful observation almost all the reaction started to form their product within 20-30 minutes of continuous refluxing. It was observed that in many reaction, formation of foam type on the top of the reaction mixture indicates the initial formation of the product which was confirmed by thin layer chromatography or simply TLC. The compounds bearing substituents of chloro and fluoro shows excellent yield. The workup procedure employed was quite simple with ice cold water wash for 3-4 times. The color of the final solid product obtained after filtration and drying gives a varied range with most of the compound exhibiting pale yellow to bright yellow. Melting point of the synthesized compounds ranges from 116-161^oC. The structure of octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives (3b-e) were elucidated by IR, ¹H-NMR, ¹³C-NMR and Mass spectroscopy.

Spectral data:

N-(4-((E)-3-(4-chlorophenyl)acryloyl)phenyl)stearamide(3a).

Pale yellow solid; yield 78%; M.P. =158-161^oC; FT-IR (KBr, cm^-1): 3,285 (NH), 3,041 (Ar-CH), 1,658 (C=O), 1,556 (C=C); ¹H NMR (300 MHz, CDCl₃), δ, ppm: 8.04-8.01(d, J = 8.72 Hz, 1H, Ar-H), 7.78-7.66 (m, 3H, Ar-H), 7.59-7.48 (m, 4H, Ar-H), 7.41-7.38 (m, 2H, HC=CH), 2.42-2.37 (t, 2H, CH₂), 1.79-1.70 (q, 2H, CH₂), 1.25 (s, 28H, (CH₂)₁₄), 0.89-0.85 (t, 3H, CH₃); ¹³C NMR (300 MHz, DMSO-d₆), δ_C, ppm: 194.17, 184.04, 174.68, 167.02, 164.16, 161.84, 132.69, 131.30, 130.60, 130.14, 128.21, 128.01, 123.72, 118.39, 31.30, 29.03, 28.81, 28.70, 22.09; MS: m/z 524.2 (M⁺).

N-(4-((E)-3-(3-chlorophenyl)acryloyl)phenyl)stearamide (3b).

Bright yellow solid; yield 82%; M.P. =118-120^oC; FT-IR (KBr, cm^-1): 3,324 (NH), 3,046 (Ar-CH), 1,662 (C=O), 1,563 (C=C); ¹H NMR (300 MHz, CDCl₃), δ, ppm: 8.18-8.15(d, J = 8.70 Hz, 1H, Ar-H), 8.08-7.92 (m, 4H, Ar-H), 7.80-7.77 (m, 3H, Ar-H), 7.49-7.45 (m, 2H, HC=CH), 6.63-6.60 (d, J = 8.81Hz, 1H, Ar-H), 2.37-2.33 (t, 2H, CH₂), 1.59-1.46 (q, 2H, CH₂), 1.22 (s, 28H, (CH₂)₁₄), 0.85-0.82 (t, 3H, CH₃); ¹³C NMR(300 MHz, DMSO-d₆), δ_C, ppm: 185.61, 171.95, 154.01, 139.63, 133.72, 131.25, 130.56, 129.99, 129.46, 127.81, 127.55, 127.47, 124.03, 118.28, 112.68, 31.25, 28.99, 28.67, 22.05, 13.91; MS: m/z 524.2 (M⁺).

N-(4-((E)-3-p-tolylacryloyl)phenyl)stearamide (3c).

Yellow solid; yield 70%; M.P. =132-135^oC; FT-IR (KBr, cm^-1): 3,309 (NH), 3,040 (Ar-CH), 1,672 (C=O), 1,556 (C=C); ¹H NMR (300 MHz, CDCl₃), δ, ppm: 8.04-8.01 (d, J = 8.16 Hz,1H, Ar-H), 7.95-7.92 (d, J = 8.46 Hz, 1H, Ar-H), 7.82-7.66 (m, 3H, Ar-H), 7.56-7.47 (m, 3H, Ar-H), 7.24-7.21 (m, 2H, HC=CH), 2.42-2.39 (m, 4H, (CH₂)₂), 1.77-1.72 (t, 3H, CH₃), 1.25 (s, 28H, (CH₂)₁₄), 0.89-0.85 (t, 3H, CH₃), ¹³C NMR(300 MHz, CDCl₃), δ_C, ppm: 187.96, 162.20, 143.74, 133.19, 129.96, 129.77, 129.49, 129.01, 128.90, 128.79, 121.17, 120.96, 118.29, 112.68, 31.25, 28.99, 22.05, 21.06, 13.91; MS: m/z 502.2 (M-1).

N-(4-((E)-3-(3-fluorophenyl)acryloyl)phenyl)stearamide (3d).

Bright yellow solid; yield 80%; M.P. =116-117^oC; FT-IR (KBr, cm^-1): 3,323 (NH), 3,040 (Ar-CH), 1,683 (C=O), 1,556 (C=C); ¹H NMR (300 MHz, CDCl₃), δ, ppm: 8.04-8.01(d, J = 8.86 Hz, 1H, Ar-H), 7.94-7.92 (d, J = 8.74 Hz, 1H, Ar-H), 7.78-7.67 (m, 2H, HC=CH), 7.55-7.49 (m, 1H, Ar-H), 7.41-7.32 (m, 4H, Ar-H), 7.14-7.06 (m, 1H, Ar-H), 2.42-2.32 (q, 2H, CH₂), 1.76-1.72 (m, 2H, CH₂), 1.25 (s, 28H, (CH₂)₁₄), 0.89-0.85 (t, 3H, CH₃); ¹³C NMR (300 MHz, CDCl₃), δ_C, ppm: 188.76, 172.07, 164.82, 161.55, 142.69, 141.86, 133.44, 131.33, 130.14, 124.63, 123.06, 119.16, 117.29, 114.09, 38.01, 32.06, 29.83, 25.60, 22.82, 14.25; MS: m/z 507.0 (M⁺).

N-(4-((E)-3-(4-methoxyphenyl)acryloyl)phenyl) stearamide (3e).

Yellow solid; yield 68%; M.P. =125-128^oC; FT-IR (KBr, cm^-1): 3,306 (NH), 3,034 (Ar-CH), 1,674 (C=O), 1,557 (C=C); ¹H NMR (300 MHz, CDCl₃), δ, ppm: 8.03-8.00(d, J = 8.42 Hz, 2H, Ar-H), 7.68-7.59 (m, 4H, Ar-H), 7.44-7.39 (m, 2H, HC=CH), 6.95-6.92 (d, J = 8.07 Hz, 2H, Ar-H), 3.86-3.85 (t, 3H, CH₃), 2.42-2.37 (t, 2H, CH₂), 1.79-1.69 (q, 2H, CH₂), 1.25 (s, 28H, (CH₂)₁₄), 0.89-0.85 (t, 3H, CH₃); ¹³C NMR (300 MHz, CDCl₃), δ_C, ppm: 189.21, 172.00, 161.80, 144.56, 142.30, 134.02, 131.13, 130.36, 129.98, 127.79, 119.57, 119.09, 114.55, 114.06, 55.53, 32.06, 29.83, 25.63, 22.82, 14.25; MS: m/z 519.0 (M⁺).

Biological activity:

The compounds 3a-3e were screened for their in vitro antibacterial activity against gram-negative bacteria (Escherichia coli) and gram-positive bacteria (Staphylococcus aureus), and antifungal activity against Penicillium italicum and Fusarium oxysporum. The activity was determined using well-diffusion method by measuring the diameter of the zone of inhibition in mm at a concentration of 10μg/uL in DMSO. The results of the antibacterial and antifungal activity of the tested compounds are presented in Table 1. All the synthesized compounds showed appreciable antibacterial activity for both gram-positive and gram-negative bacteria except compound 3e, which did not show any activity against Escherichia coli. The maximum inhibition against both Escherichia coli and Staphylococcus aureus was shown by compound 3a containing Cl substituents in para position in which the zone of inhibition was almost comparable to the standard drug.

The compounds also displayed antifungal activity against Fusarium oxysporum and Penicillium italicum. depicting its antifungal activity. All the tested compounds showed antifungal activity against Fusarium oxysporum. The maximum inhibition towards Fusarium oxysporum was exhibited by compound 3c containing methyl group and 3d containing Fluoro group. Whereas, the antifungal activity against Penicillium italicum was shown only by compound 3c, 3d and 3e, while 3a and 3b showed no potency.

Table 1. Antimicrobial activity of the tested compounds.

Zone of inhibition (mm)
Compound	*Escherichia coli*	*Staphylococcus aureus*	*Fusarium oxysporum*	*Penicillium italicum*
3a	28	29	11	-
3b	12	11	15	-
3c	16	16	19	7
3d	14	14	19	7
3e	-	15	4	9
Streptomycin	30	32	-	-
Flucanazole	-	-	28	27

CONCLUSION:

A series of novel octadecanoic acid [4-(3-phenyl-acryloyl)-phenyl]-amide chalcone derivatives (3a-e) were synthesized and characterized by various spectroscopic methods such as IR, 1H-NMR, 13C-NMR and MS. The newly synthesized chalcone compounds displayed appreciable antibacterial activity against gram-positive Escherichia coli and gram-negative Staphylococcus aureus. All the compounds except 3e showed good antibacterial activity against the tested strains, among which compound 3a exhibited the most promising antibacterial activity which was almost comparable to that of standard drug streptomycin. The results for antifungal studies indicated that all the compounds 3a, 3b, 3c, 3d and 3e exhibited antifungal activity against Fusarium oxysporum, however only compound 3c, 3d and 3e inhibited the growth of Penicillium italicum. Overall, the results revealed that the newly synthesized compounds can be of potential value in using as antifungal and antibacterial agents.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

Dr. Prabhakar M. highly acknowledges the SERB-DST, Govt. India, for the financial support (grant no.SB/EMEQ-030/2014) towards his research work. The author Shurhovolie Tsurho is grateful to UGC, India for NFHE fellowship. The authors also thank the DST-FIST, Government of India, University of Hyderabad and Nagaland University for conducting the spectral analysis.

REFERENCES:

1. John R. Sukumarana K. Kuttana G. Raob MNA. Subbarajuc V. Kuttana R. Anticancer and Antioxidant Activity of Synthetic Chalcones and Related Compounds. Cancer letters. 1995; 97(1):3–37. doi.org/10.1016/0304-3835(95)03945-s

2. Cabrera M. Simoens M. Falchi G. Lavaggi ML. Piro OE. Castellano EE. Vidal A. Azqueta A. Sagrera G. Seoane G. Synthetic Chalcones, Flavanones and Flavones as Antitumoral Agents: Biological Evaluation and Structure-Activity Relationships. Bioorganic and Medicinal Chemistry. 2007; 15(10):3356–3367. doi.org/10.1016/j.bmc.2007.03.031

3. Sharma V. Kumar V. Kumar P. Heterocyclic Chalcone Analogues as Potential Anticancer Agents. Anti-Cancer Agents in Medicinal Chemistry. 2013; 13(3):422–432.doi.org/10.2174/1871520611313030006

4. Yadav P. Lal K. Kumar A. Guru SK. Jaglan S. Bhushan S. Green Synthesis and Anticancer Potential of Chalcone Linked-1,2,3-Triazoles. European Journal of Medicinal Chemistry. 2017; 126:944–953. doi.org/10.1016/j.ejmech.2016.11.030

5. Katsori AM. Litina DH. Chalcones in Cancer: Understanding Their Role in Terms of QSAR. Current Medicinal Chemistry. 2009; 16(9):1062–1081. doi.org/10.2174/092986709787581798

6. Hsieh CT. Hsieh TJ. El-Shazly M. Chuang DW. Tsai YH. Yen CT. Wu SF. Wu YC. Chang FR. Synthesis of Chalcone Derivatives as Potential Anti-Diabetic Agents. Bioorganic & Medicinal Chemistry Letters. 2012; 22(12):3912–3915. doi.org/10.1016/j.bmcl.2012.04.108

7. Patil CB. Mahajan SK. Katti SA. Chalcone: A Versatile Molecule. Journal of Pharmaceutical Sciences and Research. 2009; 1(3):11–22. doi.org/10.1002/chin.201025251

8. Ghosh R. Das A. Synthesis and Biological Activities of Chalcones and Their Heterocyclic Derivatives: A Review. World Journal of Pharmaceutical Sciences. 2014; 3(3):578–595. doi.org/10.1002/chin.201514287

9. Kulathooran S. Selvakumar B. Dhamodaran M. Synthesis and Biological Activities of Novel Heterocyclic Chalcone Derivatives by Two Different Methods Using Anhydrous Potassium Carbonate as an Efficient Catalyst. Der Pharma Chemica. 2014; 6(3):240–249. available on https://www.derpharmachemica.com/pharma-chemica/synthesis-and-biological-activities-of-novel-heterocyclic-chalcone-derivatives-by-two-different-methods-using-anhydrous-.pdf

10. Rasool A. Panda R. Kachroo M. Synthesis of Some New Chalcone Derivatives and Evaluation of Their Anticancer Activity. International Journal of Drug Development and Research. 2013; 5(3):309–315. available on https://www.ijddr.in/drug-development/synthesis-of-some-new-chalcone-derivatives-and-evaluation-of-theiranticancer-activity.php?aid=7285

11. Dangi LL. Dulawat MS. Tiwari P. Dulawat SS. New Substituted M-Phenoxy Chalcones; Their Synthesis by Microwave Irradiation and Antifungal Activity. Asian Journal of Research in Chemistry. 2013; 6(5):461–463. available on https://ajrconline.org/HTMLPaper.aspx?PID=2013-6-5-5

12. Sharma VP. Synthesis, Characterization and Antimicrobial Screening of Some Novel Chromonyl Chalcones. Asian Journal of Research in Chemistry. 2014; 7(7):649–352. available on https://ajrconline.org/AbstractView.aspx?PID=2014-7-7-8

13. Fernandes J. Kumar A. Kumar P. Synthesis and Biological Activity of Some Novel Quinolinyl Chalcones Derived from N- Substituted 2-Quinolones Synthesis and Biological Activity of Some Novel Quinolinyl Chalcones Derived from N-Substituted. Research Journal of Pharmacy and Technology. 2013; 6(12):1336–1339. available on https://rjptonline.org/AbstractView.aspx?PID=2013-6-12-23

14. Bhat KI. Kumar A. Kumar P. Riyaz EK. Synthesis and Biological Evaluation of Some Novel Pyrimidine Derivatives Derived from Chalcones. Research Journal of Pharmacy and Technology. 2014; 7(9):995–998. available on https://rjptonline.org/AbstractView.aspx?PID=2014-7-9-25

15. Rani MS. Rohini C. keerthi BS. Mamata C. Green Synthesis of Novel Chalcone Derivatives, Characterization and Its Antibacterial Activity. Research Journal of Science and Technology. 2019; 11(3):183–185. doi.org/10.1016/j.arabjc.2013.11.018

16. Zhang HJ. Qian Y, Zhu DD. Yang XG, Zhu HL. Synthesis, Molecular Modeling and Biological Evaluation of Chalcone Thiosemicarbazide Derivatives as Novel Anticancer Agents. European Journal of Medicinal Chemistry. 2011; 46(9):4702–4708. doi.org/10.1016/j.ejmech.2011.07.016

17. Li J. Li D. Xu Y. Guo Z. Liu X. Yang H. Wu L. Wang L. Design, Synthesis, Biological Evaluation, and Molecular Docking of Chalcone Derivatives as Anti-Inflammatory Agents. Bioorganic & Medicinal Chemistry Letters. 2017; 27(3):602–606. doi.org/10.1016/j.bmcl.2016.12.008

18. Coşkun D. Tekin S. Sandal S. Coşkun MF. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones. Journal of Chemistry. 2016; 2016. doi.org/10.1155/2016/7678486

19. Mokle SS. Sayyed MA. Vibhute AY. Khansole SV. Nalwar YS. Synthesis of Some New Bioactive Chalcones and Flavones. Res. International Research Journal of Pharmacy. 2009; 2(4):846–849. available on https://rjptonline.org/AbstractView.aspx?PID=2009-2-4-111

20. Chabukswar AR. Bhanudas SK. Lokhande PD. Archana S. Ojha AML. Synthesis and Antibacterial Activity of Some Prop-2-En-1-One, Derivatives of Chalcone. Research Journal of Pharmacy and Technology. 2012; 5(11):1452–1456. available on https://rjptonline.org/AbstractView.aspx?PID=2012-5-11-10

21. Choudhary AN. Juyal V. Synthesis of Chalcone and Their Derivatives as Antimicrobial Agents. International Journal of Pharmaceutical Sciences Research. 2011; 3(3):3–6. available on https://innovareacademics.in/journal/ijpps/Vol3Issue3/2208.pdf

22. Singh S. Sharma S. Jadon PS. Synthesis and Biological Evaluation of Some New Chalcone Derivatives for Their Antimicrobial Activities. Research Journal of Pharmacy and Technology. 2012; 5(2):253–262. available on https://rjptonline.org/AbstractView.aspx?PID=2012-5-2-14

23. Jana S. Iram S. Thomas J. Liekens S. Dehaen W. Synthesis and Anticancer Activity of Novel Aza-Artemisinin Derivatives. Bioorganic and Medicinal Chemistry. 2017; 25(14):3671–3676. doi.org/10.1016/j.bmc.2017.04.041

24. Mowlana MY. Jamal A. Nasser A. Synthesis, Characterization and Microbial Activities of Novel Acetylthiophene Chalcone Derivatives. International Journal of Science and Research. 2014; 3(7):2012–2014. available on https://www.ijsr.net/get_abstract.php?PID=2014869

25. Wei Z. Chi K. Yu Z. Liu H. Sun L. Zheng C. Synthesis and Biological Evaluation of Chalcone Derivatives Containing Aminoguanidine or Acylhydrazone Moieties. Bioorganic & Medicinal Chemistry Letters. 2016; 26(24):5920–5925. doi.org/10.1016/j.bmcl.2016.11.001

26. Fang X. Yang B. Cheng Z. Zhang P. Yang M. Synthesis and Antimicrobial Activity of Novel Chalcone Derivatives. Research on Chemical Intermediates. 2014; 40(4):1715–1725. doi.org/10.1007/s11164-013-1076-5

27. Bandgar BP. Gawande SS. Bodade RG. Totre JV. Khobragade CN. Synthesis and Biological Evaluation of Simple Methoxylated Chalcones as Anticancer, Anti-Inflammatory and Antioxidant Agents. Bioorganic and Medicinal Chemistry. 2010; 18(3):1364–1370. doi.org/10.1016/j.bmc.2009.11.066

28. Ceylan M. Fındık E. Synthesis and Characterization of New Chalcone Derivatives from Cis-Bicyclo[3.2.0]Hept-2-En-6-One. Synthetic Communications. 2009; 39(6):1046-1054. doi.org/10.1080/00397910802474974

29. Singh PP. Jayalakshmi N. Kumar S. Synthesis, Characterization and Antimicrobial Evaluation of Some New Chalcones. Asian Journal of Research in Chemistry. 2013; 6(12):1133–1136. available on https://ajrconline.org/AbstractView.aspx?PID=2013-6-12-11

30. Prasad YR. Rao AL. Rambabu R. Synthesis and Antimicrobial Activity of Some Chalcone Derivatives. Journal of Chemistry. 2008; 5(3):461–466. doi.org/10.1155/2008/876257

31. Boeck P. Bandeira A. Ce P. Yunes RA. Filho VC. Torres-santos EC. Synthesis of Chalcone Analogues with Increased Antileishmanial Activity. Bioorganic and Medicinal Chemistry. 2006; 14:1538–1545. doi.org/10.1016/j.bmc.2005.10.005

32. Saxena HO. Faridi U. Kumar JK. Luqman S. Darokar MP. Shanker K. Chanotiya CS. Gupta MM. Negi AS. Synthesis of Chalcone Derivatives on Steroidal Framework and Their Anticancer Activities. Steroids. 2007; 72(13):892–900. doi.org/10.1016/j.steroids.2007.07.012

33. Venkataramireddy V. Shankaraiah M. Rao TA. Kalyani CH. Narasu LM. Varala R. Jayashree A. Synthesis and Anti-Cancer Activity of Novel 3-Aryl Thiophene-2-Carbaldehydes and Their Aryl/Heteroaryl Chalcone Derivatives. RASĀYAN Journal of Chemistry. 2016; 9(1):31–9. available on http://rasayanjournal.co.in/vol-9/issue-1/5_Vol.9,%20No.1,%2031-39,%20Jan.-March,%202016,%20RJC-1354.pdf

34. Barot VM. Gandhi SA. Mahato A. Mehta NB. Synthesis, X-Ray Diffraction Study and Antimicrobial Study of 1-(4-Butoxy-2-Hydroxyphenyl)-3-(2,5-Dimethoxyphenyl) Prop-2-En-1-One. International Journal of Science and Research. 2013; 3(2):5–8. available on http://www.ijsrp.org/research-paper-0213.php?PID=P14790

35. El-Meligie S. Taher AT. Kamal AM. Youssef A. Design, Synthesis and Cytotoxic Activity of Certain Novel Chalcone Analogous Compounds. European Journal of Medicinal Chemistry. 2017; 126:52–60. doi.org/10.1016/j.ejmech.2016.09.099

36. Sadula A. Subhashini NJP. Synthesis, Characterization and Biological Evaluation of Novel Chalcone Derivatives of Imidazolones. International Journal of Pharmacy and Biological Sciences. 2014; 5(2):433–442. available on https://www.ijpbs.net/abstract.php?article=MzM4MA==

37. Pathan IK. Babu NK. Kumar KKA. Ishwarya K. Kiran JH. Synthesis and Gastroprotective Evaluation of New Chalcone Derivatives. Research Journal of Pharmacology and Pharmacodynamics. 2013; 5(6):325–330. available on https://rjppd.org/AbstractView.aspx?PID=2013-5-6-24

38. Shahare HV. Pawar GR. Patil SS. Synthesis and Biological Evaluation of New Chalcone Analogs. Asian Journal of Research in Chemistry. 2011; 4(2):237–240. available on https://ajrconline.org/AbstractView.aspx?PID=2011-4-2-15

39. Castelli V. Zacchino SA. Lo SN. Ribas JC. Lobo G. Charris J. Corte JCG. Devia C. Rodrı M. Enriz RD. In Vitro Antifungal Evaluation and Structure-Activity Relationships of a New Series of Chalcone Derivatives and Synthetic Analogues, with Inhibitory Properties Against Polymers of the Fungal Cell Wall. Bioorganic and Medicinal Chemistry. 2001; 9(2001):1999–2013. doi.org/10.1016/s0968-0896(01)00116-x

40. Palombo EA. Semple SJ. Antibacterial Activity of Traditional Australian Medicinal Plants. Journal of Ethnopharmacology. 2001; 77(2-3):151–57. doi.org/10.1016/S0378-8741(01)00290-2

Received on 03.06.2021 Modified on 03.08.2021

Research J. Pharm. and Tech. 2022; 15(8):3412-3416.

DOI: 10.52711/0974-360X.2022.00571