A series of 1-aroyl-3-aryl thioureas derivatives were synthesized and evaluated for antibacterial activity. The results indicated that the compounds possessed higher activity against gram-negative bacteria than gram-positive bacteria. Amongst all these compounds, C18 (89.4%) exhibited the greatest antibacterial activity against gram-negative bacteria while C5 (85.6%) displayed maximum antibacterial activity against gram-positive bacteria. Preliminary study of the structure-activity relationship revealed that an electronic factor on aryl rings had a great effect on the antibacterial activity of these compounds.
The increased use of antibacterial and antifungal agents has resulted in the development of drug resistant microbial pathogens which results in failure in clinical application of these agents. This highlights the incessant need for the development of new classes of antimicrobial agents and alteration of known drugs in such way that would allow them to retain their physiological action but reduce their resistance to the pathogen. Thiourea derivatives are versatile building blocks for the synthesis of a variety of heterocyclic compounds and display a wide spectrum of biological activities such as antimicrobial [
Synthesis of some 1-aroyl-3-aryl thioureas (C1–C18) (Figure
Synthesized 1-aroyl-3-aryl thiourea derivatives.
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S. Number | Compound ID | R1 | R2 |
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1 | C1 | 2-Cl | 4-Br |
2 | C2 | 4-Cl | 3-OMe |
3 | C3 | 4-OMe | 3-OMe |
4 | C4 | 4-OMe | 2-Cl |
5 | C5 | 4-Cl | 2-Cl |
6 | C6 | 4-Cl | 4-F |
7 | C7 | 2-Cl | 3-OMe |
8 | C8 | 4-OMe | 4-Br |
9 | C9 | 2-Cl | 4-Cl |
10 | C10 | 4-Cl | 4-Cl |
11 | C11 | 4-OMe | 4-Cl |
12 | C12 | 2-Cl | 2-F |
13 | C13 | 2-Cl | 4-OMe |
14 | C14 | 4-Cl | 4-OMe |
15 | C15 | 4-OMe | 4-OMe |
16 | C16 | 4-Cl | 2-F |
17 | C17 | 4-OMe | 2-F |
18 | C18 | 2-Cl | 2-Cl |
Synthesis of 1-aroyl-3-aryl thiourea.
A solution of substituted benzoyl chloride (10 mmol) in acetone (50 mL) was added dropwise to a suspension of potassium thiocyanate (10 mmol) in acetone (30 mL) and the reaction mixture was refluxed for 30 min. After cooling to room temperature, a solution of substituted aniline (10 mmol) in acetone (10 mL) was added and the resulting mixture refluxed for 2-3 h. The reaction was monitored by performing TLC using petroleum ether : ethyl acetate (8 : 2) as mobile phase. The reaction mixture was poured into cold water and the precipitated thioureas were recrystallized using aqueous ethanol [
The structures were confirmed by spectroscopic data and elemental analyses. All the synthesized compounds were assayed in vitro for their antibacterial activity. The antibacterial activity of compounds was determined by the paper disc diffusion method using Mueller-Hinton agar medium. Sodium Penicillin G was used as the reference antibacterial agent.
Synthesis of some 1-aroyl-3-aryl thioureas (C1–C18) was carried out by treating substituted benzoyl chloride with an equimolar quantity of potassium thiocyanate in acetone followed by reaction with an equimolar amount of substituted anilines to furnish the 1-aroyl-3-aryl thiourea derivatives.
The structures were confirmed by spectroscopic data and elemental analyses. FT-IR spectrum of synthesized thiourea derivatives exhibited identical trend of stretching frequency modes. Presence of peaks in the regions 3200–3250 cm−1 and 3320–3500 cm−1 indicates the existence of NH moiety and that of peaks in the regions 1665–1695 cm−1 and 1050–1200 indicates C=O and C=S moieties, respectively, in all the compounds. NMR spectra revealed the presence of characteristic broad singlets for HN(1) and HN(3) at 9 and 12 ppm, respectively. Mass spectra of all the compounds displayed molecular ion peaks. Elemental analysis data are also in line with the theoretical values.
The synthesized compounds were assayed for their antibacterial activity against
All the synthesized compounds inhibited the growth of bacteria with zone of inhibition ranging between 4.2 and 13.1 mm and 5.2 and 14.4 mm for gram-positive bacteria and gram-negative bacteria, respectively. These compounds were found to be more active against gram-negative bacteria as compared to gram-positive bacteria. The antibacterial activity of all the compounds observed against both microorganisms is shown in Table
Zone of inhibition for samples, standard, and control.
Comp. |
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Zone of inhibition |
Relative inhibition zone diameter (in %) | Zone of inhibition |
Relative inhibition zone diameter (in %) | |
C1 | 11.7 | 72.7 | 10.9 | 71.2 |
C2 | 7.2 | 44.7 | 6.4 | 41.8 |
C3 | 10.6 | 65.8 | 9.0 | 58.8 |
C4 | 9.1 | 56.5 | 8.4 | 54.9 |
C5 | 14.2 | 88.2 | 13.1 | 85.6 |
C6 | 12.1 | 75.2 | 11.6 | 75.8 |
C7 | 8.4 | 52.2 | 7.9 | 51.6 |
C8 | 7.2 | 44.7 | 7.0 | 45.8 |
C9 | 11.5 | 71.4 | 10.4 | 68.0 |
C10 | 12.8 | 79.5 | 10.9 | 71.2 |
C11 | 7.4 | 46.0 | 7.9 | 51.6 |
C12 | 12.3 | 76.4 | 12.0 | 78.4 |
C13 | 6.4 | 39.8 | 6.0 | 39.2 |
C14 | 5.2 | 32.3 | 4.0 | 26.1 |
C15 | 5.7 | 35.4 | 4.2 | 27.5 |
C16 | 13.8 | 85.7 | 13.0 | 85.0 |
C17 | 10.6 | 65.8 | 9.4 | 61.4 |
C18 | 14.4 | 89.4 | 12.6 | 82.4 |
Standard | 16.1 |
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15.3 |
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Control |
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Standard: Sodium Penicillin G, Control: control (Solvent-DMSO).
Amongst all these compounds, C5 (85.6%) substituted with chloro group on para position of aroyl ring and fluoro group on ortho position of aryl ring exhibits maximum percentage of relative zone of inhibition and C12 (78.4%), C16 (85%), and C18 (82.4) also displayed significant antibacterial activity, while C14 (27.9%) containing fluoro and methoxy groups on para positions of aroyl and aryl ring, respectively, displayed the least percentage of relative zone of inhibition as compared with the standard drug. Following is the antibacterial efficacy of synthesized compounds against C5 > C16 > C18 > C12 > C6 > C1 > C10 > C9 > C17 > C3 > C4 > C7 > C11 > C8 > C2 > C13 > C15 > C14.
Amongst all these compounds, C18 (89.4%) carrying chloro groups on ortho positions of both aroyl and aryl rings displayed maximum antibacterial activity against C18 > C5 > C16 > C10 > C12 > C6 > C1 > C9 > C3 > C17 > C4 > C7 > C11 > C2 > C8 > C13> C15 > C14.
The synthesized compounds exhibited potent inhibitory activity against the two strains compared to standard drugs at the tested concentrations. Compounds containing chloro group at ortho position on aryl ring and chloro at para and ortho positions of aroyl ring, respectively, (C5 and C18) prove to be the active against both gram-positive and gram-negative strains, while C14 (32.3%) substituted with fluoro and methoxy groups on para positions of aroyl and aryl ring, respectively, displayed the least percentage of relative zone of inhibition as compared with the standard drug against both
The title compounds were synthesized by treating substituted benzoyl chloride with an equimolar quantity of potassium thiocyanate in acetone followed by reaction with an equimolar amount of substituted anilines to furnish the 1-aroyl-3-aryl thiourea derivatives. The synthesized thiourea derivatives were found to be more active against gram-negative bacteria as compared to gram-positive bacteria. Among the synthesized compounds, C5 and C18 exhibited maximum relative zone of inhibition against gram-positive and gram-negative strains of bacteria, respectively, as compared with the standard. These observations suggested that presence of electron withdrawing group on aryl ring is crucial for antibacterial activity.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors acknowledge the Head, School of Pharmacy, and Honorable Vice-Chancellor, Devi Ahilya University, Indore, for providing facilities for the completion of this work.