Novel thiazolidin‐4‐one clubbed thiophene derivatives via Gewald synthesis as anti‐tubercular and anti‐inflammatory agents

Abstract

In aim of obtaining novel bio‐active compounds, a new series of 5‐(3,5‐difluorophenyl)‐2‐(2‐imino‐5‐arylidene)‐4‐oxothiazolidin‐3‐yl)thiophene‐3‐carbonitrile (6a–d) and N‐(3‐cyano‐5‐(3,5‐difluorophenyl)thiophen‐2‐yl)‐2‐(substitutedamino)acetamide (7a–f) were synthesized via Gewald's method and characterized by 1H/13C nuclear magnetic resonance, Fourier‐transform infrared, mass spectrometry, and elemental analyses. All the newly prepared compounds were screened for their in vitro anti‐tubercular activity against virulent strain M. tuberculosis (H37Rv) at different concentrations ranging from 0.2 to 100 μg/ml. Most of the compounds were potent showing better inhibition at concentrations 6.25, 12.5, 25, 50, and 100 μg/ml. The anti‐inflammatory activity of the compounds was studied using inhibition of albumin denaturation technique. Tested compounds exhibited remarkable anti‐inflammatory activity. Hemolytic assay also confirmed that compounds are non‐toxic with a percentage hemolysis ranging from 1.81 to 14.94 at a concentration of 1 mg/ml. The results suggest that amino‐substituted acetamide and thiazolidin‐4‐one moiety, as well as the substitution pattern on the heterocyclic ring, have an effect on bioactivity.

Synthesis, recyclization under the action of methanol and analgetic activity of N'-(5-aryl-2-oxofuran-3(2H)-ylidene)furan-2-carbohydrazides

“…Furthermore, this method was applied to 3-imino(thiophen-2-yl)furan-2(3H)-ones derivatives, which include the pharmacophore fragment, Gewald aminothiophene [37][38][39][40][41]. Compounds that contain this pharmacophore fragment exhibit analgesic [42][43][44], anti-inflammatory [45,46], antimicrobial [47][48][49] and photoluminescent properties [50,51] and other biological activities [52][53][54]. Also, we showed that N′-[5-aryl-2-oxofuran-3(2Н)ylidene]furan-2-carbohydrazides and its precursor 4aryl-2-[2-(furan-2-ylcarbonyl)hydrazinylidene] -4oxobutanoic acids have analgesic activity in the previous studies [55].…”