DE202023100373U1 - A system for the synthesis and biological evaluation of novel urea analogues - Google Patents

Abstract

A system for the synthesis and biological evaluation of new urea analogs, the system includes:
a synthesis unit for synthesizing sulfadiazine-containing urea analogs, in which sulfadiazine is reacted with various isocyanobenzenes in a 50-ml round bottom flask using Eaton's reagent as a catalyst and solvent to synthesize urea analogs in good yield; and
an evaluation unit for conducting a biological evaluation of the produced urea analogs, wherein the antioxidant activity of the synthesized urea analogs is evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H ₂ O ₂ ) methods .

Description

FIELD OF THE INVENTION

The present disclosure relates to a system for the synthesis and biological evaluation of novel urea analogs. In particular, the present disclosure relates to the synthesis of novel sulfadiazine-bearing urea analogs by a one-pot green two-component protocol and the subsequent evaluation of the antioxidant activities for all synthesized compounds.

BACKGROUND OF THE INVENTION

The urea cycle involves the synthesis of urea in the bodies of numerous species. Urea is produced in the liver and excreted in the urine of mammals, as well as in the blood of plants, birds, yeast and many other microbes. Aromatic urea analogues such as N-phenyl-N-(2-chloroethyl)urea and heterocyclic urea derivatives exhibit good anticancer activity (RTKs) due to their potent inhibitory activity against receptor tyrosine kinases. Transketolase is inhibited by derivatives of diphenylurea.

Analogs of urea exhibit beneficial biological properties, including inhibitory, antibacterial, and anticancer properties of anaplastic lymphoma kinase (ALK). Urinary therapy, fertilizer, vehicle, laboratory, antiviral, anti-inflammatory, agricultural, industrial, anti-HIV, malaria, antibacterial, antioxidant and enzyme urease are just a few of the many uses for urea.

One of the most important antibiotics in medicine is sulfadiazine, also known as the sulfa drug or a member of the sulfonamide group. This drug is applied topically to treat burns and wound infections, as well as urinary tract infections, and is used in both human and veterinary therapy. Therefore, there is a need to develop urea analogs containing sulfadiazine.

In view of the above discussion, it is clear that there is a need for a system for the synthesis and biological evaluation of new urea analogs.

SUMMARY OF THE INVENTION

The present disclosure relates to a system for the synthesis and biological evaluation of novel urea analogs. In the present disclosure, novel urea analogs (compounds 3a-3d) are synthesized using a two-component, green, one-pot method using an environmentally friendly reagent from Eaton. These compounds are powerful antioxidant therapeutic candidates. Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) techniques, all compounds are evaluated for in vitro antioxidant studies. At different doses of 25, 50, 75 and 100 g/ml, compounds 3a and 3c showed significant antioxidant activity compared to the reference drug ascorbic acid in both DPPH and H2O2 assays. Of all the synthetic compounds, compounds 3a and 3c have the strongest antioxidant activity. Excellent yields, fast reaction times, a straightforward work-up technique, no column chromatography required, and potential antioxidants are just a few advantages of the protocol.

The present disclosure seeks to provide a system for the synthesis and biological evaluation of new urea analogs. The system includes: a synthesis unit for synthesizing sulfadiazine-containing urea analogs, wherein sulfadiazine is reacted with various isocyanobenzenes in a 50 ml round bottom flask using Eaton's reagent as a catalyst and solvent to synthesize urea analogs in good yield; and an evaluation unit for conducting a biological evaluation of the produced urea analogs, wherein the antioxidant activity of the synthesized urea analogs is evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H ₂ O ₂ ) methods becomes.

An aim of the present disclosure is to provide a system for the synthesis and biological evaluation of new urea analogs.

Another object of the present disclosure is to employ a one-pot, green, two-component protocol for the synthesis of novel urea analogs.

Another object of the present disclosure is the use of Eaton's reagent as a catalyst and solvent in the synthesis of novel urea analogs.

Another object of the present disclosure is to conduct an evaluation of the antioxidant activities of all new urea analog compounds (Compound 3a-3d).

Yet another object of the present disclosure is to compare the antioxidant properties of the urea analogs to standard drug ascorbic acid.

In order to further clarify the advantages and features of the present disclosure, the invention will be described in more detail with reference to specific embodiments thereof illustrated in the accompanying drawings. It should be understood that these drawings represent only typical embodiments of the invention and are therefore not to be considered as limiting its scope. The invention will be described and illustrated with additional specificity and detail with the accompanying drawings.

character list

• 1 veranschaulicht ein Blockdiagramm eines Systems zur Synthese und biologischen Bewertung neuer Harnstoffanaloga gemäß einer Ausführungsform der vorliegenden Offenbarung;
• 2 das Schema zur Synthese neuer Harnstoffanaloga gemäß einer Ausführungsform der vorliegenden Offenbarung darstellt;
• 3 die Strukturen der synthetisierten Harnstoffverbindungen (3a-3d) gemäß einer Ausführungsform der vorliegenden Offenbarung darstellt; und
• 4A und 4B veranschaulichen Tabellen, die die Ergebnisse darstellen, die aus Antioxidansstudien der hergestellten neuen Harnstoffanaloga unter Verwendung von DPPH- und Wasserstoffperoxidverfahren gemäß einer Ausführungsform der vorliegenden Offenbarung erhalten wurden.

These and other features, aspects and advantages of the present disclosure will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like characters represent like parts throughout the drawings, wherein:

• 1 illustrates a block diagram of a system for the synthesis and biological evaluation of novel urea analogs according to an embodiment of the present disclosure;
• 2 depicts the scheme for synthesizing novel urea analogs according to an embodiment of the present disclosure;
• 3 Figure 12 illustrates the structures of the synthesized urea compounds (3a-3d) according to an embodiment of the present disclosure; and
• 4A and 4B Figure 12 illustrates tables presenting the results obtained from antioxidant studies of the prepared novel urea analogs using DPPH and hydrogen peroxide methods according to an embodiment of the present disclosure.

Furthermore, those skilled in the art will appreciate that elements in the drawings are presented for simplicity and may not necessarily be drawn to scale. For example, the flowcharts illustrate the method in terms of the salient steps involved to help improve understanding of aspects of the present disclosure. Moreover, with respect to the construction of the device, one or more components of the device may have been represented in the drawings by conventional symbols, and the drawings may only show such specific details as are relevant to an understanding of the embodiments of the present disclosure around the drawings not to be obscured with details that would be readily apparent to one of ordinary skill in the art benefiting from the description contained herein.

DETAILED DESCRIPTION:

For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and specific language will be used to describe the same. It should be understood, however, that no limitation on the scope of the invention is intended thereby, contemplating such changes and further modifications to the illustrated system, and such further applications of the principles of the invention illustrated therein, as would normally occur to one skilled in the art to which the invention relates.

Those skilled in the art will understand that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting.

Reference throughout this specification to "an aspect," "another aspect," or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure is. Thus, the phrases "in one embodiment," "in another embodiment," and similar phrases throughout this specification may, but need not, all refer to the same embodiment.

The terms "comprising," "comprising," or other variations thereof are intended to cover non-exclusive inclusion such that a process or method that includes a list of steps includes not only those steps but may include other steps not expressly listed or any inherent in such process or procedure. Similarly, without further limitation, one or more devices or subsystems or elements or structures or components preceded by "comprises...a" does not exclude the existence of other devices or other subsystems or other elements or other structures or other components or additional devices or additional subsystems or additional elements or additional structures or additional components.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly defined by one of ordinary skill in the art is understood to which this invention pertains. The system, methods, and examples provided herein are illustrative only and are not intended to be limiting.

Embodiments of the present disclosure are described below in detail with reference to the accompanying drawings.

1 Figure 1 illustrates a block diagram of a system for the synthesis and biological evaluation of novel urea analogs according to an embodiment of the present disclosure. The system (100) includes a synthesis unit (102) for synthesizing sulfadiazine-containing urea analogs, wherein sulfadiazine is reacted with various isocyanobenzenes in a 50 mL round bottom flask using Eaton's reagent as a catalyst and solvent to synthesize urea analogs in good yield.

In one embodiment, an evaluation unit (104) is used to perform a biological evaluation of the synthesized urea analogs, wherein the antioxidant activity of the synthesized urea analogs is measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H ₂ O ₂ ) methods.

In one embodiment, a one-pot, green, two-component protocol for synthesizing urea analogs is employed.

In one embodiment, during the synthesis of urea analogs, the mixture of all compounds is allowed to stir for a period of 3 hours using thin layer chromatography (TLC) to monitor reaction progress.

In one embodiment, after the reaction is complete, the resultant obtained is purified by passage through a silica gel column using hexane:ethyl acetate (7:3) as eluent to obtain urea analogs.

In one embodiment, for the simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay and the hydrogen peroxide radical assay to study the radical scavenging activity of the synthesized urea analogs, ascorbic acid is used as a positive control for comparison of antioxidant activities.

In one embodiment, in the case of a simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, the absorbance of the incubated test samples is measured at a wavelength of 517 nm using a UV-Vis spectrometer, and in the case of the hydrogen peroxide Radical test, the absorbance of test samples and phosphate buffer without hydrogen peroxide is measured at a wavelength of 230 nm.

2 illustrates the scheme for synthesizing novel urea analogs according to an embodiment of the present disclosure. Using a one-pot, two-component green technique, new urea analogs are synthesized with sulfadiazine. Sulfadiazine (0.001 mol) (1) and various isocyanobenzenes (0.001 mol) 2(ad) are reacted in a 50 mL round bottom flask with 5 drops of Eaton's reagent (P2O5:CH3SO2OH) as catalyst and solvent. The reaction was stirred for 3 hours. Thin layer chromatography (TLC) is used to monitor the progress of the reaction. Hexane : ethyl acetate (7:3) is used as eluent after the reaction is complete to purify the resulting solid and produce the urea analogs 3(ad) (Scheme 1) in good to excellent yields (89-94%). .

3 illustrates the structures of the synthesized urea compounds (3a-3d) according to an embodiment of the present disclosure. The R structures of compounds 3a, 3b, 3c and 3d are shown in this figure with yield percentages of 92, 96, 89 and 93, respectively. Namely, the compounds prepared are 4-(3-(4-Nitrophenyl)ureido)-N-phenylbenzenesulfonamide (3a) 4-(3-(4-Chlorophenyl)ureido)-N-phenylbenzenesulfonamide (3b), 4-(3-( 3-Bromophenyl)ureido)-N-phenylbenzenesulfonamide (3c) and 4-(3-(3-Fluorophenyl)ureido)-N-phenylbenzenesulfonamide (3d).

4A and 4B Figure 12 illustrates tables presenting the results obtained from antioxidant studies of the prepared novel urea analogs using DPPH and hydrogen peroxide methods according to an embodiment of the present disclosure. Figure 4A shows the table presenting the results of the DPPH radical assay. The free radical scavenging activity of the synthesized compounds (3a-3d) is assayed using a simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. The antioxidant activity of the compounds is compared to ascorbic acid, which served as a positive control. To prepare a solution with a concentration of 0.004% DPPH, 4 mg of DPPH was dissolved in 100 ml of methanol. The compounds prepared are diluted with methanol to produce various concentrations (25, 50, 75 and 100 g/mL). One milliliter of each of these test solutions is added to four milliliters of DPPH:methanol solution in a set of test tubes, which are then incubated for 30 minutes in the dark with periodic shaking. a UV A visible spectrophotometer is used to determine the absorbance of the test samples at 517 nm. The percentage of DPPH scavenger activity was calculated by the formula given below. $$\%Hemm\mathrm{and}nGvOnDPPH=\frac{\left(Ab{s}_{KOnt\mathrm{right}Olle}-Ab{s}_{P\mathrm{right}Obe}\right)}{Ab{s}_{KOnt\mathrm{right}Olle}}\times 100$$

Where "Abs - _Control " represents the absorbance of the DPPH solution and "Abs - _Sample " represents the absorbance of the sample and the DPPH solution.

Figure 4B shows the results obtained from antioxidant activity analysis using the hydrogen peroxide method. The newly synthesized compounds 3(ad) have a high scavenging capacity for hydrogen peroxide radicals. A solution of hydrogen peroxide (40 mM) in phosphate buffer is prepared at a pH range of 7.4 to 7.5. Concentrations of 100 g/mL of the test compounds were then added to the H 2 O 2 solution in 3.4 mL of phosphate buffer (0.6 mL, 40 mM). The test tubes are occasionally shaken while incubating in the dark for 30 minutes. The absorbance of the test materials and the phosphate buffer without hydrogen peroxide is determined at 230 nm using a UV spectrophotometer. The standard drug is ascorbic acid, which is used to compare antioxidant activities. Using the formula provided below, the amount of hydrogen peroxide scavenging activity is determined. $$\%Hemm\mathrm{and}nGvOn{H}_2{\mathrm{<figure-callout\; id="2"\; label="O"\; filenames="DE202023100373U1\_0004.png"\; state="\{\{state\}\}">O</figure-callout>}}_2=\frac{\left(Ab{s}_{KOnt\mathrm{right}Olle}-Ab{s}_{P\mathrm{right}Obe}\right)}{Ab{s}_{KOnt\mathrm{right}Olle}}\times 100$$

Where the Abs _control was the absorbance of standard H ₂ O ₂ ; Abs _sample was the absorbance in the presence of sample and standard H ₂ O ₂ .

The drawings and the above description provide exemplary embodiments. Those skilled in the art will recognize that one or more of the elements described may well be combined into a single functional element. Alternatively, certain elements can be broken down into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, orders of processes described herein may be changed and are not limited to the manner described herein. Furthermore, the actions of any flowchart need not be implemented in the order shown; also, not all actions have to be performed. Actions that are not dependent on other actions can also be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples. Numerous variations, whether or not expressly stated in the description, such as differences in structure, dimensions and use of materials, are possible. The scope of the embodiments is at least as broad as indicated by the following claims.

Benefits, other advantages, and solutions to problems have been described above with respect to specific embodiments. However, the benefits, advantages, fixes, and components that may cause benefits, benefits, or solutions to occur or become more pronounced are not to be construed as critical, required, or essential features or components of any or all claims.

reference list

100

A system for the synthesis and biological evaluation of novel urea analogues.

102

synthesis unit

104

evaluation unit

Claims (6)

A system for the synthesis and biological evaluation of new urea analogs, the system comprising: a synthesis unit for synthesizing sulfadiazine-containing urea analogs, wherein sulfadiazine is reacted with various isocyanobenzenes in a 50 ml round bottom flask using Eaton's reagent as catalyst and solvent, to synthesize urea analogues in good yield; and an evaluation unit for conducting a biological evaluation of the produced urea analogs, wherein the antioxidant activity of the synthesized urea analogs is evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H ₂ O ₂ ) methods becomes. system after claim 1 , using a one-pot green two-component protocol for synthesizing urea analogs. system after claim 1 , wherein during the synthesis of urea analogues the mixture of all compounds is allowed to stir for a period of 3 hours using thin layer chromatography (TLC) to monitor the progress of the reaction. system after claim 3 , after completion of the reaction, the result obtained is purified by passing it through a silica gel column using hexane: ethyl acetate (7:3) as eluent to obtain urea analogues. system after claim 1 , where for the simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical test and the hydrogen peroxide radical test to study the radical scavenging activity of the synthesized urea analogues, ascorbic acid is used as a positive control to compare the antioxidant activities. system after claim 5 , where in the case of a simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical test, the absorbance of the incubated test samples is measured at a wavelength of 517 nm using a UV-Vis spectrometer, and in the case of the hydrogen peroxide radical test the absorbance of test samples and phosphate buffer without hydrogen peroxide is measured at a wavelength of 230 nm.

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