Synthesis and In-Vitro/Silico Evaluation of Fluorinated Chalcones

Introduction

The shikimate route produces chalcones, phenolic phytochemicals of the flavonoid class. Flavonoids can trace their biosynthesis back to chalcones. In chemical terms, chalcones are usually alkenones that consist of two rings of ketones joined by a three-carbon bond. This class may also include dihydrochalcones and other saturated ketones ¹. These ketones have a three-carbon alkenone unit rather than an alkenone unit. One or more phenolic hydroxyl functionalities, phenyl and geranyl substitutions on the aromatic rings, and other distinguishing features are found in naturally occurring chalcones. Some 3,000 chalcones have been identified in nature², and many of these have been shown to modulate and protect cells through interactions with other biomolecules. Cytotoxic, anti-inflammatory, anticancer, antioxidant, and antimitotic effects of chalcones and their derivatives have been the subject of multiple articles and patents³. Chalcone derivatives have been extensively studied for their bioactivities and bioinspired syntheses because of their medicinal potential and structural simplicity⁴. The natural product containing chalcone scaffold with a medicinal application. Chalcones enjoy a privileged status in medicinal chemistry because of their natural abundance and relative simplicity in synthetic chemistry. Many scientists have generated synthetic chalcones since the nineteenth century. Kostanecki and Tambor⁵ were the first to synthesize chalcones by treating o-acetoxychalcone dibromides with an alcoholic alkali. Modern methods of synthesizing chalcones^6-8 involve forming the core chalcone nucleus from two aromatic ring molecules, like benzaldehyde and acetophenone, by combining an alkaline base with a polar solvent. Many researchers synthesize chalcone in unique ways such as ultrasonic, microwave, solvent-free, grinding, etc. ^9-12. These techniques are very important today because they reduce energy, avoid hazardous reagents, and environmental risks, reduce wastewater pollution, protect biological life, save the environment, and save time.

Herein, we report the efficient strategy for the synthesis of a series of structurally interesting chalcone derivatives. A base-catalyzed condensation of FMAA with benzaldehydes to synthesize a series of chalcone derivatives in chemical, ultrasonic, and solvent-free grinding methods. B. subtilis MCC 2010 and S. aureus MCC 2408 are used for Gram-positive bacteria testing, while E. coli MCC 2412 and P. aeruginosa MCC 2080 are used for Gram-negative bacteria testing, to develop more effective and less toxic antibacterial medications. The structural features regulating the interaction of produced derivatives with an identified receptor were also elucidated using molecular docking techniques.                                     

Experimental

Materials and Methods

All of the synthetic chemical reagents and solvents utilized in this study were of the highest purity and were sourced from trustworthy suppliers. Borosilicate labware was used, an 8 x 8 x 6 cm Grinding bowl, and a pestle made of Ceramic material used for grinding purposes. For sonication use an ultrasonic 6.5 lit bath. The open capillary tubes were used to find the uncorrected melting points of the compounds that were produced. Using thin-layer chromatography (TLC), with silica gel as the stationary phase and pet ether and ethyl acetate as the mobile phases, we were able to confirm the reaction’s progress and the product’s conversion. Under ultraviolet light, each spot could be seen for what it was. An FT-IR spectrometer from Brucker was utilized to record the IR spectra, while a 400 MHz spectrometer, also from Brucker, was employed to capture the ¹H NMR spectra.

The general procedure of compound 1a-j

The synthesis involved the use of FMAA along with substituted aromatic benzaldehydes in the presence of a base and alcohol as the solvent, we present an efficient procedure for synthesizing a sequence of chalcones (1a-j). The typical pathway of a synthetic reaction is shown in Figure 1 below.

Figure 1: Reaction scheme of compound 1a-j Click here to View Figure

Chemical

Chalcones are synthesized using the Claisen-Schmidt condensation method. A solution was produced in 5 mL of ethanol with 1.31 mmol of FMAA and 1.31 mmol of substituted benzaldehydes. The solution was then supplemented with NaOH (1.97 mmol). Until the reaction was verified by TLC, the mixture was stirred at ambient temperature. The chalcone was then filtered out after the mixture was neutralized with diluted HCl at 0°C. The crude chalcone was refined by recrystallization in alcohol to yield (1a-j).

Ultra-sonication

Added 1.31 mmol of FMAA, 1.31 mmol of substituted benzaldehydes, and 1.97 mmol of NaOH in a test tube. The resultant mixture was raised to room temperature and agitated under ultrasonic radiation until the product (1a-j) was converted entirely to TLC. Once the reaction was complete, the solid chalcones (1a-j) were obtained by cooling the interacting components in an ice bath and neutralizing them by dil. HCl. The chalcone is recrystallized from alcohol.

Grinding

In a clean Grinding bowl and pestle 1.31 mmol of FMAA, 1.31 mmol of substituted benzaldehydes, and 1.97 mmol of NaOH at room temperature. Grind the mixture for several minutes, the solid product was observed which was checked in TLC. Once confirmed the complete absence of acetophenone the solid chalcones (1a-j) were obtained by cooling the interacting components in an ice bath and neutralizing by dil. HCl. The chalcone is recrystallized from alcohol.

The listed chalcones (1a-j) were synthesized using the method mentioned above.

Table 1: The listed chalcones (1a-j) were synthesized using the method mentioned above Click here to View Table

Spectral data of synthesis compound (1a-j)

(E)-1-(4-fluoro-3-methylphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one,

White solid, yield = 79.38%; m.p. 155°C. FT-IR (KBr) cm⁻¹: 3023 (Ar-CH₃), 2972 (-CH=), 2929 (C-CH₃), 1659 (C=O, chalcone), 1590 (C=C), 1243 (C-F), 1146 (C-OCH₃), 738 (Tri. Sub benz. Ring), 681 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.385 (s, 3H, CH₃), 3.944 (s, 3H, -OCH₃), 6.964 (d, 2H, -CH=), 6.964-8.164 (m, 7H, Aromatic H). Anal. calcd for C₁₆H₁₃FO₂: C, 75.54; H, 5.59; F, 7.03; O, 11.84.

(E)-1-(4-fluoro-3-methylphenyl)-3-(3-methoxyphenyl)prop-2-en-1-one,

Off-white solid, yield = 81.0%; m.p. 157°C. FT-IR (KBr) cm⁻¹: 3029 (Ar-CH₃), 2973 (-CH=), 2929 (C-CH₃), 1660 (C=O, chalcone), 1591 (C=C), 1250 (C-F), 1146 (C-OCH₃), 740 (Tri. Sub benz. Ring), 623 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.386 (s, 3H, CH₃), 3.950 (s, 3H, -OCH₃), 6.968 (d, 2H, -CH=), 7.012-8.166 (m, 7H, Aromatic H). Anal. calcd for C₁₆H₁₃FO₂: C, 75.54; H, 5.59; F, 7.03; O, 11.84.

(E)-1-(4-fluoro-3-methylphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one,

Off-white solid, yield = 84.63%; m.p. 155°C. FT-IR (KBr) cm⁻¹: 3027 (Ar-CH₃), 2974 (-CH=), 2922 (C-CH₃), 1660 (C=O, chalcone), 1585 (C=C), 1250 (C-F), 1153 (C-OCH₃), 751 (Tri. Sub benz. Ring), 683 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.366-2.540 (s, 3H, CH₃), 3.858 (s, 3H, -OCH₃), 7.043-7.063 (d, 2H, -CH=), 7.314-8.166 (m, 7H, Aromatic H). Anal. calcd for C₁₆H₁₃FO₂: C, 75.54; H, 5.59; F, 7.03; O, 11.84.

(E)-3-(2,4-dimethoxyphenyl)-1-(4-fluoro-3-methylphenyl)prop-2-en-1-one,

Off-White solid, yield = 74.0%; m.p. 159°C. FT-IR (KBr) cm⁻¹: 3012 (Ar-CH₃), 2968 (-CH=), 2939 (C-CH₃), 1649 (C=O, chalcone), 1592 (C=C), 1256 (C-F), 1144 (C-OCH₃), 761/715 (Tri. Sub benz. Ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.365 (s, 3H, CH₃), 3.968-3.944 (s, 6H, -OCH₃), 6.921 (d, 2H, -CH=), 7.087-7.914 (m, 6H, Aromatic H). Anal. calcd for C₁₆H₁₃FO₃: C, 71.99; H, 5.71; F, 6.33; O, 15.98.

(E)-3-(3-chlorophenyl)-1-(4-fluoro-3-methylphenyl)prop-2-en-1-one,

White solid, yield = 73.91%; m.p. 156°C. FT-IR (KBr) cm⁻¹: 3025 (Ar-CH₃), 2971 (-CH=), 2927 (C-CH₃), 1662 (C=O, chalcone), 1594 (C=C), 1241 (C-F), 738 (Tri. Sub benz. Ring), 688 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.368 (s, 3H, CH₃), 7.120 (d, 2H, -CH=), 7.142-7.923 (m, 7H, Aromatic H). Anal. calcd for C₁₆H₁₃FOCl: C, 69.95; H, 4.40; F, 6.92; O, 5.82; Cl, 12.91.

(E)-1-(4-fluoro-3-methylphenyl)-3-(2-fluorophenyl)prop-2-en-1-one,

Light yellow solid, yield = 70.60%; m.p. 157°C. FT-IR (KBr) cm⁻¹: 3065 (Ar-CH₃), 2978 (-CH=), 2924 (C-CH₃), 1657 (C=O, chalcone), 1586 (C=C), 1235 (C-F), 752 (Tri. Sub benz. Ring), 625 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.393 (s, 3H, CH₃), 7.122-7.144 (d, 2H, -CH=), 7.166-7.944 (m, 7H, Aromatic H). Anal. calcd for C₁₇H₁₄F₂O: C, 74.41; H, 4.66; F, 14.71; O, 6.20.

(E)-1-(4-fluoro-3-methylphenyl)-3-(3-fluorophenyl)prop-2-en-1-one,

Yellow solid, yield = 73.31%; m.p. 159°C. FT-IR (KBr) cm⁻¹: 3042 (Ar-CH₃), 2981 (-CH=), 2922 (C-CH₃), 1659 (C=O, chalcone), 1583 (C=C), 1219 (C-F), 756 (tri. Sub benz. ring), 624 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.377 (s, 3H, CH₃), 7.112-7.151 (d, 2H, -CH=), 7.156-7.934 (m, 7H, Aromatic H). Anal. calcd for C₁₇H₁₄F₂O: C, 74.41; H, 4.66; F, 14.71; O, 6.20.

(E)-1-(4-fluoro-3-methylphenyl)-3-(2,4,6-trifluorophenyl)prop-2-en-1-one,

Off-whit solid, yield = 75.68%; m.p. 163°C. FT-IR (KBr) cm⁻¹: 3057 (Ar-CH₃), 2933 (-CH=), 2919 (C-CH₃), 1664 (C=O, chalcone), 1587 (C=C), 1245 (C-F), 739 (tri. Sub benz. ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.383 (s, 3H, CH₃), 7.032-7.120 (d, 2H, -CH=), 7.142-7.928 (m, 5H, Aromatic H). Anal. calcd for C₁₇H₁₄F₄O: C, 65.31; H, 3.43; F, 25.83; O, 5.44.

(E)-3-(2,3-dimethoxyphenyl)-1-(4-fluoro-3-methylphenyl)prop-2-en-1-one,

White solid, yield = 80.00%; m.p. 161°C. FT-IR (KBr) cm⁻¹: 3012 (Ar-CH₃), 2936 (-CH=), 2833 (C-CH₃), 1615 (C=O, chalcone), 1584 (C=C), 1262 (C-F), 1150 (C-OCH₃), 745 (tri. Sub benz. ring), 686 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.326 (s, 3H, CH₃), 3.798-3.889 (s, 6H, -OCH₃), 7.086 (d, 2H, -CH=), 7.342-8.183 (m, 6H, Aromatic H). Anal. calcd for C₁₈H₁₇FO₃: C, 71.99; H, 5.71; F, 6.33; O, 15.98.

(E)-3-(2,5-dimethoxyphenyl)-1-(4-fluoro-3-methylphenyl) prop-2-en-1-one,

Off-White solid, yield = 87.50%; m.p. 159°C. FT-IR (KBr) cm⁻¹: 3010 (Ar-CH₃), 2935 (-CH=), 2838 (C-CH₃), 1612 (C=O, chalcone), 1589 (C=C), 1264 (C-F), 1148 (C-OCH₃), 747 (tri. Sub benz. ring), 686 (di. Sub benz ring).  ¹H NMR (400 MHz, CDCl₃, δ ppm): 2.326-2.379(s, 3H, CH₃), 3.798-3.889 (s, 6H, -OCH₃), 7.086(d, 2H, -CH=), 7.331-8.162 (m, 6H, Aromatic H). Anal. calcd for C₁₈H₁₇FO₃: C, 71.99; H, 5.71; F, 6.33; O, 15.98

Disc-Diffusion Study

We evaluated the antibacterial activity of the azomethine compound using the disc diffusion method ¹³. We used discs made from Whatman’s filter paper no.1, each with a diameter of 6 millimeters. The 500 mg/mL concentration of chalcones solution was prepared. To cultivate the bacteria, 20 mL of sterile growth media was poured into each sterile petri dish, covered, and placed in the refrigerator to solidify. After incubating the broth cultures of microorganisms for 16 hours, we performed disc diffusion studies ^14,15. The sample, control, and standard discs were air-dried at room temperature after sterilization and infection to remove any leftover solvent that could impact the results. For bacteria, the zone of inhibition appears after 24 hours of incubation at 37 °C on plates that were chilled for 1 hour to increase the rate of chemical diffusion from the test disc into the agar plate ¹⁶.

In-Silico (Molecular Docking) Study

The docking and virtual screening were performed as per the established protocol from our lab that is published elsewhere ^17-21. To further understand how the synthesized compounds interact with pathogenic microbial species at the molecular level, molecular docking experiments were conducted. The PyRx domain took advantage of Open Babel to bring in ligand molecules in SDF format for energy reduction with the UFF Force field. The Python Prescription 0.8 (PyRx) package, of which AutoDock 4.2 is a component, was used.²². On an affinity grid with 50 points at each of the three X, Y, and Z coordinates and a spacing of 0.375A, the Autogrid program was used to cover the entire active site. We employed a Lamarckian genetic algorithm to perform the conformational search for the optimal binding pose. The three-dimensional receptor-ligand interaction and two-dimensional chemical interaction structures were shown using the Biovia Discovery Studio17.1.0 ²³. Three bacteria and one fungus were used in the in-silico assessment of the antifungal and antibacterial activity. E. coli glutaredoxin (PDB ID: 1GRX) and Pseudomonas aeruginosa UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetyl glucosamine deacetylase (PDB ID: 3P3E) were two of the Gram-negative bacteria targets. Staphylococcus aureus DNA gyrase (PDB ID: 3G75) and dihydrofolate reductase (PDB ID: 1AI9) were chosen as targets for gram-positive bacteria and fungi, respectively. Protein Data Bank (http://www.rcsb.org) was consulted to get the three-dimensional structures of the ligand-coated targets. The most effective compounds against Candida albicans, according to an in vitro investigation, were 1a, 1c, and 1d, which also showed strong binding affinity in an in-silico study. Similar antibacterial and antifungal studies were conducted, and Table 2 shows their binding affinities.

Results and Discussion

Chemistry

Chalcones (1a-j) were synthesized by reacting FMAA with aromatic benzaldehydes in the presence of dilute alkali²⁴. The chalcones derivatives of the FMAA moiety illustrated in Figure 1 were synthesized from FMAA and substituted benzaldehydes at an equimolar concentration in the presence of the basic catalyst sodium hydroxide. All chalcone compounds are non-hygroscopic, insoluble in water, and resistant to various organic solvents, making them stable at room temperature. All prepared organic compounds had structures confirmed by UV-visible, IR, and NMR spectrum data. The freshly synthesized azomethines were discovered to have maxima in the wavelength range of 275-440 nm (λ_max).

FT-IR Spectra

The experimental section summarizes the infrared frequencies displayed by the benzaldehyde substituents of FFMAA derivatives. A band of moderate intensity, corresponding to the aromatic n(C-H) frequency range, was seen for FMAA derivatives. The novel chalcones with an aromatic (-CH₃) group showed poor broadband in the 2922-2968 cm^-1 range²⁵. Bands at 2939–2981 cm^-1 in the FTIR spectra of the newly discovered derivatives are associated with the -CH= stretching vibration. The (C=O) group is responsible for a prominent band in the infrared spectra of all chalcones compounds, centered at 1649-1664 cm^{-1 26-27}. The aromatic n (C=C) vibrations are responsible for the medium intensity band between 1583 and 1594 cm^-1.  In the spectra, we observed the (C-F) band around 1219-1256 cm^-1 in derivatives of FMAA with benzaldehyde substituents.

Compounds 1a-1d, 1i, and 1j included the -OCH₃ group on the aromatic ring, which caused the appearance of the medium intensity band at 1144-1153 cm^{-1 28}.). C-Cl stretching vibration explains the band’s appearance at 1241 cm^-1 in compound 1e.

¹H-NMR Spectra

In the ¹H-NMR spectra of compound 1a-j, the methyl group protons are assigned to two singlets at 2.36-2.39 ppm. All of the synthesized chalcones exhibited two doublets in the range 6.90-7.12 and 6.92-7.14 ppm in their 1H NMR spectra ²⁹, corresponding to typical coupling constants (J) of 15.3 and 15.1 Hz, respectively, confirming their production. The aromatic proton of synthesized new chalcones has a multiplet peak at 6.96-8.16 ppm integrating³⁰. For compounds 1a-1d, 1i, and 1j, a singlet peak at 3.94-3.97 ppm for three protons may be attributed to -OCH₃.

Antibacterial activity

The bacterial strains were used in the disc diffusion method of antimicrobial tests. Table 2 summarizes the MICs of the chalcone derivatives against the four distinct bacterial strains. Three of the 10 heterocyclic chalcones tested showed substantial activity against E. coli MCC 2412. The conventional medication was effective against Bacillus subtilis MCC 2010 MCC 2080, whereas compounds 1a-j with fluoro substituents on the phenyl ring exhibited even greater action. Pseudomonas aeruginosa MCC 2080 was resistant to the reference medication and all compounds except those with a phenyl moiety (1a-j). This compound’s antimicrobial effectiveness against Pseudomonas aeruginosa MCC 2080 indicated its promise to treat drug-resistant bacteria. Some compounds with fluoro or bromo substituents were effective against the bacteria, whereas others were only moderately or ineffective ^31-34. Compound 1d exhibits significant activity against S. aureus MCC 2408, Bacillus subtilis MCC 2010, and E. coli MCC 2412 due to its meta and para substituent methoxy groups. Compound 1c exhibits a similar effect on antibacterial activity against Pseudomonas aeruginosa MCC 2080 due to its para methoxy group.

Table 2: Antibacterial activities of compounds 1a-j

Compound (1a-j)	Antibacterial Activity (zone of inhibition)
	S. aureus (MCC2408)	B. subtilis (MCC2010)	E. coli (MCC2412)	P. aeruginosa (MCC2080)
a	6	9	0	8
b	9	11	6	7
c	6	6	9	22
d	24	23	24	6
e	6	8	8	0
f	7	0	6	7
g	6	8	7	10
h	9	7	6	0
i	6	6	9	10
j	7	8	16	7
Streptomycin	7	6	10	18

Figure 2: Antibacterial activity of compounds 1a-j Click here to View Figure

Antifungal Activity

In this work, C. albicans (MCC1439) and S. cerevisiae (MCC1033) were subjected to a MIC of 50 g/ml of fluconazole. Based on the results presented in Table 3, all compounds examined possessed a fungicidal potential superior to the reference medication, with a MIC of 54 g/ mL against Candida albicans (MCC1439) and Saccharomyces cerevisiae (MCC1033).

Table 3: Antifungal activities of compounds 1a-j

Compound (1a-j)	Antifungal Activity (zone of inhibition)
	C Albicans (MCC1439)	S. C. (MCC1033)
a	7	0
b	6	0
c	7	8
d	8	0
e	6	8
f	8	11
g	9	6
h	7	8
i	6	7
j	0	12
Fluconazole	9	6

 

Figure 3: Antifungal activity of compounds 1a-j Click here to View Figure

In-silico (Molecular Docking) study

Ten compounds 1a-j were docked in bacterial and fungal proteins as mentioned above. To gain more insights about the compounds, interactions were studied in detail. As shown in Figure 4, 3P3E interacts best with compound 1d. The compound forms hydrogen bonds with residues Thr190, Phe191; Van der Waals interactions with Leu18, Ser63, His78, Thr75 Asp241, His237, Phy160, Ile158, Lys261, Ser262, Gly263 and a Pi-alkyl interaction with residue His19. The second bacterial protein 3G75 shows the highest binding affinity for compound 1d as shown in Figure 5. It shows hydrogen bonding with residues Ser55, Asp54, Van der Waals interaction with Glu58, Ile102, Ser128, Val130, Leu103, Thr173, Val131, Glu 50. The third bacterial protein 1GRX best interacts with the compound 1c as shown in Figure 6. It forms a hydrogen bond with residues Thr73, Van der Waals interaction with Ser14, Gly57, Thr58, Ser9, Asp74, and a carbon-hydrogen bond Lys45. The antifungal protein 1AI9 shows the highest binding affinity with compound 1d as shown in Figure-7. The compound forms a hydrogen bond with Ala11, Van der Waals interaction with Gly23, Tyr 21, Thr147, Gly20, Lys24, Glu32, Ile112, Tyr118, Gly114, Val10 and a pi stacked: Phe 36. 

Table 4: The enthalpy of binding of the freshly produced chemicals (ΔG).

Sr No	Fungi	Bacteria
Compounds (1a-j)	C.albicans (1AI9)	Pseudomonas. a (3P3E)	E.coli (1GRX)	Staphylococcus. a (3G75)
a	-6.51	-6.54	-5.68	-5.99
b	-6.77	-6.22	-5.97	-5.55
c	-6.74	-6.17	-5.43	-5.65
d	-6.55	-6.30	-5.47	-5.62
e	-6.74	-6.39	-5.88	-5.8
f	-6.71	-6.08	-5.62	-5.41
g	-6.69	-6.29	-5.56	-5.96
h	-6.40	-5.60	-5.36	-5.24
i	-6.43	-6.38	-5.73	-6.72
j	-6.54	-6.50	-5.24	-6.08

 

Figure 4: The 3D and 2D images demonstrate the binding interactions between chemical 1d and the amino acids of 3P3E. Click here to View Figure

Figure 5: Covalent interactions between chemical 1d and the amino acids in 3G75, are shown in 3D and 2D. Click here to View Figure

Figure 6: Compound 1c’s binding interactions with 1GRX’s amino residues, are depicted in 3D and 2D. Click here to View Figure

Figure 7: Compound 1d’s binding interactions with 1AI9’s amino acids are depicted in 3D and 2D. Click here to View Figure

Conclusion

This study discusses the synthesis, characterization, and antibacterial and antifungal properties of substituted benzaldehyde derivatives of FMAA. These compounds’ structures were investigated using UV, ¹H NMR, and FT-IR spectrum spectroscopy. The process defined as a chemical route and ultrasonic, grinding, solvent-free reaction which delivers a suitable yield was used to synthesize these new chalcone derivatives. These methods are very significant in today’s world because they save time, safeguard biological life, reduce wastewater pollution, and reduce energy and environmental dangers. Subsequently, the antibacterial effects of the fluorinated chalcones (1a-j) were evaluated against bacterial strains. These compounds exhibited superior antibacterial activity compared to streptomycin and demonstrated efficacy against a broad spectrum of bacteria. Compounds 1c and 1d were identified as interesting candidates for the development of new antifungal and antibacterial inhibitors based on their binding free energy. Our goal is to determine the mechanism of action of newly synthesized derivatives (1a-j) in the inhibition of 3P3E, 1GRX, 3G75, and 1AI9 through in vitro observation and structural analysis of the docked complex.

Acknowledgment

The author would like to express their gratitude toward the principal and chemistry department of Yogeshwari Mahavidyalaya, Ambajogai College, for giving the necessary research support. The author would like to express gratitude to Dr. Babasaheb Ambedkar of Marathwada University in Aurangabad and Savitribai Phule of Pune University for their assistance.

Conflict of Interest

The authors assert that there are no conflicts of interest.

Funding Sources

There is no funding sources

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