Antimicrobial, Antioxidant, and Anticancer Activities of Some Novel Isoxazole Ring Containing Chalcone and Dihydropyrazole Derivatives

Abstract

Our previous work identified isoxazole-based chalcones and their dihydropyrazole derivatives as two important five-membered heterocycles having antitubercular activity. Hence, in the present study, we biologically evaluated 30 compounds, including 15 isoxazole ring-containing chalcones (17–31) and 15 dihydropyrazoles (32–46) derived from these chalcones for their antimicrobial, antioxidant, and anticancer activities. Chalcones exhibited superior antibacterial and antioxidant activities compared to dihydropyrazoles. Among the chalcones, compound 28 showed potent antibacterial (MIC = 1 µg/mL) and antioxidant activities (IC50 = 5 ± 1 µg/mL). Dihydropyrazoles, on the contrary, demonstrated remarkable antifungal and anticancer activities. Compound 46 (IC50 = 2 ± 1 µg/mL) showed excellent antifungal activity whereas two other dihydropyrazoles 45 (IC50 = 2 ± 1 µg/mL) and 39 (IC50 = 4 ± 1 µg/mL) exhibited potential anticancer activity. The compounds were also tested for their toxicity on normal human cell lines (LO2) and were found to be nontoxic. The active compounds that have emerged out of this study are potential lead molecules for the development of novel drugs against infectious diseases, oxidative stress, and cancer.

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

“…It was previously mentioned (see Section 5.3.1 ) that oxazolines exhibited inferior anticancer activities compared to their pyrazoline analogues as exemplified by 32 in the case of oxindole hybrids. However, chalcone derived isoxazole-pyrazoline hybrids have displayed interesting cytotoxic activities [ 144 ]. Compound 65 ( Figure 23 ) was found to be the most potent among 15 analogues against human prostate cancer cell DU-145 (IC 50 = 2 μg/mL) while it was non-toxic (IC 50 > 40 μg/mL) against normal human cells (L02).…”

Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

“…Obviously, this fact is crucial and is fully consistent with the results of other studies on antibacterial activities. [ 25,49 ] It is noteworthy that the growth of spore microorganisms ( Bacillus subtilis ) is suppressed to a higher degree than non‐spore ones ( Enterococcus durans ). A standard aminoglycoside antibiotic, Gentamicin, was used for the comparison.…”

“…[ 19 ] At the same time, many derivatives of isoxazole (including natural ones, chalcones, hispolons) possess immunomodulatory, anticancer, anti‐inflammatory, anticonvulsant, anti‐diabetic, antitubercular, antiviral and antimicrobial properties. [ 20–25 ]…”

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

“…The in vitro antiproliferative activity of chalcones ( 2 to 16 ) and dihydropyrazoles ( 17 to 31 ) was evaluated by Mosmann’s MTT assay, as described previously [ 28 ] on prostate cancer cell lines (DU-145). The antiproliferative activity of the compounds was determined their IC 50 values.…”

“…Compounds containing dihydropyrazole skeletons have been reported to possess varied activities such as antibacterial, antifungal, anticancer, analgesic, and anti-inflammatory activities [ 16 , 17 , 18 , 19 , 20 ]. We have previously reported various phenyl-substituted and heterocycle-based chalcones and dihydropyrazoles with significant antioxidant, antibacterial, antifungal, antitubercular, cytotoxic, and anticancer activities [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Previous reports published in the literature suggest that the presence of chalcones ( Figure 1 I,II) and dihydropyrazoles ( Figure 1 III,IV) substituted with chlorine and other substituents such as heterocycle-based chalcones and dihydropyrazole derivatives are essential structural features for biological activities including antifungal, antibacterial, anticancer, and antioxidant activities [ 2 , 5 , 15 , 29 , 30 , 31 , 32 , 33 ].…”