Synthesis, Anticancer, Antimicrobial and Antioxidant Potential of Novel 4-(Substituted phenyl-1,3,4-oxadiazol/thiadiazol-2-yl)-4-(4-substituted phenyl) Azetidin-2-One Derivatives

by Selleckchem | Oct 16 2023

By exploiting the ample biological potential of 1,3,4-oxadiazole/thiadiazole ring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. Various substituted azetidin-2-one derivatives have been identified as immunostimulating and antimicrobial, as well as their antioxidant activity. 2-amino 1,3,4 oxadiazole/thiadiazole conjugates were synthesized by mixing semi/thio carbazides and sodium acetate with water and stirring well, followed by adding aldehydes in methanol at room temperature. Acetate (glacial) was used as the catalyst to produce Schiff's bases (intermediates) by treating substituted aldehydes with 2-amino 1,3,4 oxadiazole/thiadiazole(s). Using the mixture of triethylamine (dropwise) and chloroacetylchloride with vigorous stirring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. The newly synthesized conjugates were evaluated for their anticancer potential using MCF-7 cell lines. Amoxicillin and fluconazole were used as reference drugs to determine their antimicrobial activity. Synthesized derivatives were evaluated for their antioxidant properties using 2-diphenyl-1-picrylhydrazyl (DPPH). In vitro cytotoxicity screening (MTTS assay) revealed that derivatives AZ-5, 9, 10, 14 and 19 demonstrated high efficacy with the percentage of inhibition at different concentration ranges (0.1 μM, 0.5 μM, 1 μM, 2 μM) of 89% to 94% μM as compared to doxorubicin as standard drug. The antimicrobial study indicated that compounds AZ-10, 19, and AZ-20 were found to have significant antimicrobial potential with MIC ranges of 3.34 µM to 3.71 µM in comparison to reference drugs having 4.29 µM to 5.10 µM. Based on antioxidant screening, most of the synthetic derivatives showed greater stability and effectiveness than the standard drug. According to the antioxidant screening, compounds AZ-5 and AZ-15 (IC50 = 45.02 μg/mL and 42.88 μg/mL, respectively) showed the greatest potency, as compared to ascorbic acid (IC50 = 78.63 μg/mL). Structure-activity relationship (SAR) studies of synthesized novel derivatives revealed that para-substituted halogen and nitro derivatives have remarkable potential against MCF-7 cancer cell lines and different microbial strains. Current evidence indicates that the synthesized derivatives may be promising candidates for use in the prevention and treatment of these infections. These synthesized compounds require further mechanism-based research to understand how they interact with the cells.

Comments:

The paragraph you provided describes the synthesis and evaluation of a series of compounds derived from 1,3,4-oxadiazole/thiadiazole rings. The compounds were prepared by introducing various substitutions on a 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one scaffold. These derivatives have been found to possess immunostimulating, antimicrobial, and antioxidant activities.

The synthesis of the compounds involved several steps. First, 2-amino 1,3,4-oxadiazole/thiadiazole conjugates were synthesized by mixing semi/thio carbazides and sodium acetate with water, followed by the addition of aldehydes in methanol at room temperature. This reaction resulted in the formation of Schiff's bases as intermediates. The next step involved the use of chloroacetylchloride in the presence of triethylamine to prepare the final 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives.

The synthesized compounds were then evaluated for their potential as anticancer agents using MCF-7 cell lines, a commonly studied breast cancer cell line. The results showed that several derivatives, namely AZ-5, 9, 10, 14, and 19, demonstrated high efficacy with inhibition percentages ranging from 89% to 94% at different concentrations. These compounds exhibited better efficacy than the standard drug doxorubicin.

Additionally, the antimicrobial activity of the compounds was assessed using amoxicillin and fluconazole as reference drugs. Compounds AZ-10, 19, and AZ-20 displayed significant antimicrobial potential, with minimum inhibitory concentration (MIC) ranges of 3.34 µM to 3.71 µM. The MIC values of the reference drugs were slightly higher, ranging from 4.29 µM to 5.10 µM.

The antioxidant properties of the synthesized derivatives were evaluated using the 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results indicated that most of the compounds exhibited greater stability and effectiveness than the standard drug used in the study. Compounds AZ-5 and AZ-15 displayed the highest potency, with IC50 values of 45.02 μg/mL and 42.88 μg/mL, respectively, compared to the IC50 value of 78.63 μg/mL for ascorbic acid, which was used as a reference.

The structure-activity relationship (SAR) studies of the synthesized derivatives revealed that derivatives with para-substituted halogen and nitro groups showed remarkable potential against MCF-7 cancer cell lines and various microbial strains. These findings suggest that the synthesized compounds have potential for use in the prevention and treatment of infections. However, further research is needed to investigate the mechanisms through which these compounds interact with cells.

In conclusion, the paragraph summarizes the synthesis, evaluation, and potential applications of 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives. These compounds exhibited anticancer, antimicrobial, and antioxidant activities, making them promising candidates for further study and development.