Novel pyrazole‐clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti‐inflammatory agents

Abstract

The aim of this study was to synthesize newer potent Schiff bases by condensing 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile and 1,3-disubstituted-1Hpyrazole-4-carbaldehydes, and to investigate their biological activity. The compounds were synthesized via Gewald synthesis and characterized by spectral data and elemental analyses. They were screened for their in vitro antibacterial and antiinflammatory activities. The synthesized compounds were also evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using the microplate Alamar Blue assay. Compounds 8b, 8c, 8f, 8g, 8k, 8n, and 8o showed promising antibacterial activity. The interactions between the substituted pyrazoles and bovine protein showed promising anti-inflammatory activity. The experimental results revealed compound 8a as a promising antitubercular agent. Hemolytic assays confirmed that the compounds are nontoxic, with percentage hemolysis ranging from 3.6 to 20.1, at a concentration of 1 mg/ml. The results suggest that the pyrazole ring and the substitution pattern on the heterocyclic moiety have an effect on the bioactivity.

Thiophene‐containing compounds with antimicrobial activity

“…[123] While none of these azomethines had any significant antimicrobial activity when In a follow-up article, [124] another series of Schiff bases 137 (Figure 14), which were obtained through the condensation of the been also disclosed. [125] The generally superior results in antimicrobial activity of this series should presumably be due to the re- chromen-2-yl) (Figure 14) had a modest anti-B. subtilis activity (MIC > 32 μM).…”

Structural Insights into Pyrazoles as Agents against Anti‐inflammatory and Related Disorders

“…The compounds substituted at meta position of the phenyl ring exhibited good anti-inflammatory activity. [117] 7. Bicyclic fused pyrazoles…”

“…Compound 84 with electron withdrawing group like p ‐chlorophenyl at C‐3 of pyrazole ring exhibited better anti‐inflammatory activity with IC 50 of 34.1 μg/ml compared to the diclofenac (31.4 μg/ml). The compounds substituted at meta position of the phenyl ring exhibited good anti‐inflammatory activity [117] …”

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

“…As 1,3-disubstituted-1 H -pyrazole-4-carbaldehydes 74 were synthesized by Vilsmeier–Haack reaction of hydrazones 73 ( Scheme 33 ). Subsequently, a reaction of 74 with 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile ( 75 ) in the presence of a catalytic amount of glacial acetic acid in ethanol provided 76 in good yields ( Scheme 33 ) [ 69 ]. The obtained products were then evaluated for their antibacterial, anti-inflammatory, and antitubercular studies.…”