Synthesis, biological evaluation and in silico studies of some new analogues of 3,5-vdisubstituted thiazolidin-2,4-dione.

Background: A new series of 3,5-disubstituted thiazolidin-2,4-dione molecules were derived and characterized using various spectral techniques (1H NMR, IR, carbon, hydrogen, nitrogen, etc.) and physicochemical parameters. Materials & methods: The molecules were derived using Knoevenagel condensation followed by Mannich reaction and further synthesized analogues were screened for their antioxidant and antimicrobial potential using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method and serial tube dilution method, respectively, along with in silico studies (docking and absorption, distribution, metabolism and excretion parameters) to explore the drug-receptor interaction and druglikeness. Results & conclusion: In antimicrobial screening, the analogs MP2, MM6, MM7 and MM8 displayed promising activity while molecule MM4 exhibited better antioxidant potential in the series. In molecular docking analysis, the best-fitted analogs, namely, MM6 and MM7, showed good interactions.

Thiazolidin-2,4-Dione Scaffold: An Insight into Recent Advances as Antimicrobial, Antioxidant, and Hypoglycemic Agents.

Heterocyclic compounds containing nitrogen and sulfur, especially those in the thiazole family, have generated special interest in terms of their synthetic chemistry, which is attributable to their ubiquitous existence in pharmacologically dynamic natural products and also as overwhelmingly powerful agrochemicals and pharmaceuticals. The thiazolidin-2,4-dione (TZD) moiety plays a central role in the biological functioning of several essential molecules. The availability of substitutions at the third and fifth positions of the Thiazolidin-2,4-dione (TZD) scaffold makes it a highly utilized and versatile moiety that exhibits a wide range of biological activities. TZD analogues exhibit their hypoglycemic activity by improving insulin resistance through PPAR-γ receptor activation, their antimicrobial action by inhibiting cytoplasmic Mur ligases, and their antioxidant action by scavenging reactive oxygen species (ROS). In this manuscript, an effort has been made to review the research on TZD derivatives as potential antimicrobial, antioxidant, and antihyperglycemic agents from the period from 2010 to the present date, along with their molecular mechanisms and the information on patents granted to TZD analogues.

Synthesis, biological evaluation and in-silico ADME studies of novel series of thiazolidin-2,4-dione derivatives as antimicrobial, antioxidant and anticancer agents.

BACKGROUND: A novel series of thiazolidine-2,4-dione molecules was derived and their chemical structures were established using physiochemical parameters and spectral techniques (1H-NMR, IR, MS etc.). The synthesized molecule were then evaluated for their antioxidant, anticancer and antimicrobial potential. RESULTS AND DISCUSSION: Serial tube dilution method was employed to evaluate the antimicrobial potential against selected fungal and bacterial strains by taking fluconazole and cefadroxil as reference antifungal and antibacterial drugs respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity was used to assess the antioxidant potential of the synthesized analogues. Further, the anticancer potential of the selected molecules was assessed against DU-145 cancer cell lines using MTT assay. The drug-likeness was also evaluated by studying in-silico ADME parameters of the synthesized analogues. CONCLUSION: In antioxidant evaluation studies, the analogue H5 with IC50 = 14.85 µg/mL was found to be the most active molecule. The antimicrobial evaluation outcomes suggested that the molecules H5, H13, H15 and H18 possessed moderate to promising activity against the selected species of microbial strains having MIC range 7.3 µM to 26.3 µM. The results of anticancer evaluation revealed that all the screened derivatives possess mild anticancer potential. The in-silico ADME studies revealed that all the compounds were found to be drug-like.

Quinoxaline: A Chemical Moiety with Spectrum of Interesting Biological Activities.

Quinoxaline (C8H6N2), commonly called 1,4-diazanaphthalene, 1,4-benzodiazine, or benzopyrazine, is a very potent nitrogenous heterocyclic moiety consisting of a benzene ring fused with the pyrazine ring. A number of different methods for the synthesis of quinoxaline derivatives have been reported in the literature, but the most effective method, commonly used for the synthesis of quinoxaline analogues involves the condensation of substituted o-phenylenediamines with 1, 2- dicarbonyl compounds in the presence of different catalyst(s). The presence of different types of catalysts and their concentration affects the overall yield of the product. Quinoxaline not only plays an important role as an organic reaction intermediate but also has a wide spectrum of interesting biological activities viz. antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal activity, etc. Some commercially available drug molecules containing quinoxaline moiety are echinomycin (as antibacterial, antineoplastic, and nucleic acid inhibitor), triostins (cyclic desipeptide as an antibacterial agent), dioxidine and mequindox (as antibacterial agents), carbadox (controlling swine dysentery), desoxycarbadox (as swine growth promoter) and panadipion (as hepatoprotective agent), etc. A large number of quinoxaline analogues possessing different biological activities and their synthetic procedures have been patented worldwide.