Recent advances bioactive 1,2,4-triazole-3-thiones.

Resistance to antibiotics is a major global problem and there is an urgent need to develop new therapeutic agents. Although many classes of active compounds have been established as efficient derivatives in diverse fields of antimicrobial therapy, they have not yet found wide application against a few deadly microbes. In recent years, compounds have been developed that have solved some of the problems posed; for example improved bioavailability is one of the targets achieved with most of the more recent compounds, allowing for once-daily dosing. Benzofuran and its derivatives are found to be suitable structures, existing widely in natural products and unnatural compounds with a wide range of biological and pharmacological applications; thus, considerable attention has been focused on the discovery of new drugs in the fields of drug invention and development. Some benzofuran derivatives, such as psoralen, 8-methoxypsoralen and angelicin have been used in the treatment of skin diseases such as cancer or psoriasis. The unique structural features of benzofuran and its wide array of biological activities make it a privileged structure in the field of drug discovery, especially in the search for efficient antimicrobial candidates. Recently, this scaffold has emerged as a pharmacophore of choice for designing antimicrobial agents that are active toward different clinically approved targets. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we collated the published reports on this versatile core to provide a deeper insight, so that its full therapeutic potential can be utilized for the treatment of microbial diseases. This study systematically provides a comprehensive report on current developments in benzofuran-based compounds as antimicrobial agents and is also helpful for the researchers working on a substitution pattern around the nucleus, with an aim to help medicinal chemists to develop structure activity relationships (SAR) on these derivatives as antimicrobial drugs.

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Benzofuran: an emerging scaffold for antimicrobial agents

A review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives

Benzofuran compounds are a class of compounds that are ubiquitous in nature. Numerous studies have shown that most benzofuran compounds have strong biological activities such as anti-tumor, antibacterial, anti-oxidative, and anti-viral activities. Owing to these biological activities and potential applications in many aspects, benzofuran compounds have attracted more and more attention of chemical and pharmaceutical researchers worldwide, making these substances potential natural drug lead compounds. For example, the recently discovered novel macrocyclic benzofuran compound has anti-hepatitis C virus activity and is expected to be an effective therapeutic drug for hepatitis C disease; novel scaffold compounds of benzothiophene and benzofuran have been developed and utilized as anticancer agents. Novel methods for constructing benzofuran rings have been discovered in recent years. A complex benzofuran derivative is constructed by a unique free radical cyclization cascade, which is an excellent method for the synthesis of a series of difficult-to-prepare polycyclic benzofuran compounds. Another benzofuran ring constructed by proton quantum tunneling has not only fewer side reactions, but also high yield, which is conducive to the construction of complex benzofuran ring systems. This review summarizes the recent studies on the various aspects of benzofuran derivatives including their important natural product sources, biological activities and drug prospects, and chemical synthesis, as well as the relationship between the bioactivities and structures.

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Natural source, bioactivity and synthesis of benzofuran derivatives

The synthesis of novel series of benzofuran derivatives, containing barbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl) methylidene]pyrimidin-2,4,6(1H,3H,5H)-trione (4a–i) and thiobarbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl)methylidene]-2-thioxodihydropyrimidin-4,6(1H, 5H)-dione (5a–i) have been reported. The target compounds (4a–i) and (5a–i) were synthesized by the Knoevenagel condensation of (5-substituted-1-benzofuran-2-yl)(2/4-substitutedphenyl) methanone (3a–i) with barbituric acid and thiobarbituric acid, respectively, in acid medium. These compounds were screened for the antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 4a, 5a, 4c, and 5c displayed good antibacterial and antifungal activity against all tested strains. Further, the synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate synthase and the compounds 4c and 5c have emerged has an active antimicrobial agent with least binding energy (−5.27 and −4.85 kJ mol−1). Compounds 4e, 4f, 5e, and 5f showed promising free radical scavenging activity and compounds 5a and 5b showed good chelating ability with Fe2+ ions.

Synthesis, antimicrobial, and antioxidant activity of benzofuran barbitone and benzofuran thiobarbitone derivatives

Previously unknown biphenyl containing 5-phenyl-1-benzofuran-2-yl derivatives; methanones (2a–i), tertiary alcohols (3a–l), and carbinols (4a–f) were synthesized and evaluated for their antimicrobial and antioxidant activities to study the effect of functionalization at the carbonyl carbon and substitution at biphenyl ring on these activities. The introduction of hydroxyl group at carbonyl carbon enhanced the antioxidant property (3a, 3g, 3h, 4a, and 4b), while antimicrobial activity decreased; the carbinol and tertiary alcohols corresponding to methanone 2a and 2b showed no antimicrobial activity. Biphenyl methanones 1, 2a, 2f, and 2g exhibited antimicrobial activity with minimal inhibitory concentration ranging between 0.001 and 0.500 mg/mL, tertiary alcohols 3a, 3g, and 3h and carbinols 4a and 4b exhibited the promising antioxidant property. The mode of action of these active compounds was carried out by docking of receptor GlcN6P synthase with newly synthesized candidate ligands 1, 2a, 2e, 2f, 2g, 2h, 3a, 3g, 3h, 4c, and 4d.

5-phenyl-1-benzofuran-2-yl derivatives: synthesis, antimicrobial, and antioxidant activity

A series of 1,2,4-triazole-based Schiff base heterocyclic compounds (5a-f and 8a-i) and phenethylamines (7a-h) were synthesized and evaluated for antioxidant properties by free-radical scavenging, anti-hemolytic activity, lipid peroxidation, and their protective effects against DNA oxidative damage. Compounds 7c, 7d, 7h, 8b, and 8i showed promising DPPH(•) radical scavenging activity with the level of inhibition between 86.8% and 94%. Compounds 8a, 8b, 8d, 8g, and 8i were effective against the oxidative hemolysis of human erythrocytes and lipid peroxidation, in a dose-dependent manner, with IC50 values in the range of 55.7-80.7 and 53.2-81.2 µg/mL, respectively. Compounds 8a and 8b were effective against oxidative damage on erythrocyte ghost membrane proteins, and 8g and 8i were able to protect against DNA oxidative damage.

Synthesis and evaluation of antioxidant properties of novel 1,2,4-triazole-based schiff base heterocycles.

The facile transformation of aryl/heteroaryl nonaflates into corresponding amides via Pd-catalyzed aminocarbonylation using Mo(CO)6 as a solid CO source under microwave-enhanced condition is reported. The method was found to be tolerant with respect to a diverse range of electronically biased aryl/heteroaryl nonaflates, and exceptional yields were obtained. The optimized protocol was further extended to a diverse range of amines.

Raghu Ningegowda

Papers

5-phenyl-1-benzofuran-2-yl derivatives: synthesis, antimicrobial, and antioxidant activity

Synthesis and evaluation of antioxidant properties of novel 1,2,4-triazole-based schiff base heterocycles.

Mo(CO)6 as a solid CO source in the synthesis of aryl/heteroaryl weinreb amides under microwave-enhanced condition