Synthesis of thiophene-pyrazole conjugates as potent antimicrobial and radical scavengers

Abstract

The current study presents the synthesis of thiophene-appended pyrazoles through 3+2 annulations of chalcones 3(a-g) with aryl hydrazine hydrochlorides 4(a-d) in acetic acid (30%) under reflux conditions produced the thiophene-pyrazole hybrids 5(a-g) in good yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, and elemental analysis. Further, preliminary biological evaluation studies show that compounds 5b and 5f having chloro substitution only in the thiophene ring exhibited excellent inhibition (12.5-25.0 µg/mL) against all the tested organisms in comparison with that of the standard. Compounds, 5a, 5c and 5g having electronegative chloro substitutions each in the aromatic and thiophene rings showed excellent (12.423-31.213 µg mL -1 ) DPPH radical scavenging potencies. The synthesis of pyrazoline derivatives and the efficacy of some of the synthesized molecules as antimicrobial and antioxidant agents validate the significance of this study.

Synthesis of novel Schiff bases using 2-Amino-5-(3-fluoro-4-methoxyphenyl)thiophene-3-carbonitrile and 1,3-Disubstituted pyrazole-4-carboxaldehydes derivatives and their antimicrobial activity

“…M. G. Prabhudeva et al, in 2018 reported the synthesis of bioactive thiophene-pyrazole conjugates and screened further for their antimicrobial and anti-oxidant properties. Their biological evaluation studies showed that compounds containing chloro substitution only in the thiophene ring exhibited excellent inhibition against all the tested organisms in comparison with that of the standard drug ciproflaxin [32].…”

Thiophene‐containing compounds with antimicrobial activity

“…Claisen-Schmidt condensation of 2-acetyl-5-chlorothiophene with substituted benzaldehydes afforded a series of chalcone analogs, which underwent cyclocondensation with two phenylhydrazines to give pyrazolines 45 (Figure 5), whose antimicrobial activity was examined. [54] Compounds…”

“…Claisen–Schmidt condensation of 2‐acetyl‐5‐chlorothiophene with substituted benzaldehydes afforded a series of chalcone analogs, which underwent cyclocondensation with two phenylhydrazines to give pyrazolines 45 (Figure 5), whose antimicrobial activity was examined. [ 54 ] Compounds 45 (R 1 = R 2 = OCH 3 ; R = H, R 1 = R 2 = CH 3 ; R = H) had a broad spectrum activity, being at least equipotent to ciprofloxacin (MIC = 12.5–25 μg/ml) and nystatin (MIC = 25–50 μg/ml) against all the microbial strains under investigation. In addition, pyrazoline 45 (R 1 = R 2 = OCH 3 ; R = Cl) was equipotent to ciprofloxacin (12.5 μg/ml) against P. aeruginosa , while pyrazoline 45 (R 1 = N(CH 3 ) 2 ; R 2 = H; R = Cl) was equipotent to nystatin (12.5 μg/ml) against C. albicans .…”

Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

“…Synthesis of pyrazoles substituted by thiophene moiety 29 could be carried during the reaction of chalcone-type compound 28 with phenyl hydrazine hydrochloride 4 -HCl via 3 + 2 annulations ( Scheme 13 ). The obtained thiophene-pyrazole hybrids 29 were screened as antimicrobial and antioxidant agents ( Scheme 13 ) [ 50 ].…”