Bioactive Heterocycles Research Articles

Enzyme-catalyzed synthesis of bioactive heterocycles

Abstract Enzymes are proteins that functions as biological catalyst. It is now a known fact that enzyme can catalyze many synthetic operations better than the conventional reagents. Not only in the synthesis of natural products, they can also be applied for construction of varieties of unnatural compounds. In this chapter, Pariyar and Ghosh have discussed in brief synthesis of various biologically active heterocyclic compounds using different enzymes as catalysts. Among various enzymes, laccases, trypsin, α-amylase and Bakers’ yeast are few that are easily available and have been extensively explored for various synthetic strategies. This chapter will definitely serve as valuable source of information to the readers in the field of enzyme-catalyzed reactions.

Microwave-assisted C-C and C-Heteroatom Bond Formations in an Aqueous Medium

In recent times, microwave-assisted chemistry has gained enormous attraction in organic synthesis owing to its versatile advantages such as avoidance of harsh reaction condition, increase of yield, elimination of by-product, shorter reaction time and removal of wastages. Besides, water as a reaction medium further includes more benefits as it eliminates all the drawbacks of toxic solvent, which may cause injuries for our mother earth. Furthermore, C-C and C-heteroatom bond formation reactions are very significant as most of the drug as well as bioactive compounds contain heterocycles or C-hetero bond, which is a key tool of chemistry. This article demonstrates the advancement on the topic of microwave assisted C-C and C-heteroatom bond formation reactions in aqueous medium.

Ultrasound-Promoted Sustainable Synthesis and Antimicrobial Evaluation of 2-Aryl Benzimidazoles Catalyzed by BPAE at Room Temperature

Background: Present-day chemists are more interested in developing and using green chemistry protocol for various organic transformations, which employ natural feedstock extracts, and solvent-free, and greener catalysts; they are well known for their non-hazardous nature and have replaced many organic and inorganic based catalysts. In literature, the reported homogenous catalytic approaches have been employed for various bioactive heterocycle syntheses, which follow the green chemistry principle established for various organic transformations catalyzed by WERSA, BFE, WEPPA, WEMFSA, WEMPA, and Eichhorniacrassipes. Among them, 2-aryl benzimidazole derivatives have emerged as prominent molecules with a wide variety of applications in biological and material science. Methods: The agro-waste sourced from the banana peel is utilized for the preparation of BPAE catalyst, which is employed for the synthesis of 2-aryl benzimidazole derivatives under ultrasound waves at room temperature. Results: Here, 2-Aryl benzimidazoles synthesized through the reaction of a substituted o-phenylene diamine with substituted benzoyl chloride catalyzed by BPAE under ultrasound waves at room temperature are described. Furthermore, catalyst BPAE is characterized by flame emission spectrometry, SEM-EDX, and XRD techniques. Conclusion: The present work established an eco-friendly, sustainable and novel approach for the synthesis of 2-aryl benzimidazoles using natural feedstock BPAE. The major merits of BPAE include its use as an agro-waste-derived catalyst. It is also highly abundant, inexpensive, yields faster reactions, has a simple workup, and does not require the use of column chromatography.

Design, Synthesis and Antibacterial Activity screening of Novel Bis cyclic Imides Linked to Trimethoprim Drug

Cyclic imides are well known important organic compounds that exhibit diverse biological activities like anti - inflammatory, antibacterial, analgesic, hypoglycemic and antifungal activities. Besides these compounds are useful building blocks in the synthesis of many drugs and pharmaceuticals. On the other hand trimethoprim is a well-known antibiotic that is used in combination with Sulfamethoxazole in treating urinary tract infections, bacterial infections and acute invasive diarrhea. Moreover Schiff bases represent the most active intermediates that exhibit wide spectrum of biological activities and play a vital role in the production of different pharmaceutical and bioactive heterocycles. Based on all these facts, it seems worthwhile to design and synthesize new molecules that contain these three active moieties (cyclic imide, trimethoprim and Schiff base) together in the same molecule since this may exhibit the new compounds high biological activity and may open possibilities for fighting bacterial infections.

Green synthesis, cytotoxicity and antimicrobial activities of some new pyrazolines, pyrimidines and naphthyridines based on 1,3-di(thien-2-yl)prop-2-en-1-one using choline chloride-urea mixture as a deep eutectic solvent

An efficient and facile green synthesis of chalcone derivatives 1a-d was achieved by treatment of aromatic aldehydes with 2-acetylthiophene in the presence of choline chloride-urea mixture as a deep eutectic solvent. Chalcone 1a was used as a reactive key precursor to design a series of bio-active heterocycles such as pyrimidine, pyrazoline, pyridine, pyridopyrimidine and naphthyridine. The Structural formula of derivatives were confirmed and characterized by their elemental analyses and spectral data (IR, MS, 1H NMR, 13C NMR). In addition, the synthesized derivatives were evaluated for their antimicrobial activities, it was found that compounds 3, 8 and 9a exhibited potent antifungal activity in comparison with the standard drug. Cytotoxicity against breast cancer (MCF7) was screened also and most compounds showed low to moderate activity. The results of the viral screening against HBV of selected compounds indicated that compounds (9b, 15), 8, (3, 6), and 5 showed moderate viral replication inhibition.

Synergistic Catalytic Effect of the Combination of Deep Eutectic Solvents and Hierarchical H-TiO2 Nanoparticles toward the Synthesis of Benzimidazole-Linked Pyrrolidin-2-One Heterocycles: Boosting Reaction Yield

Synthesis of bioactive heterocyclic compounds comprising pyrrolidinone linked to a benzimidazole moiety by an eco-friendly and efficient route was investigated. The targeted scaffolds were synthesized from substituted arylamines and available o-phenylenediamine under ultrasonic irradiation in the presence of a mixture of a deep eutectic solvent (DES) and hierarchical TiO2 (H-TiO2) microspheres as a green catalytic system. Two DESs were synthesized by separately mixing FeCl2 and CuCl2 with urea. On the other hand, hierarchical TiO2 (H-TiO2) was synthesized by a solvothermal route and characterized by XRD, SEM, Raman spectroscopy, and XPS. The results demonstrate that the best reaction yields are obtained by using H-TiO2 microspheres in the DES. Besides, the synthesized compounds were screened for their antibacterial activity against different bacteria. Overall, eight derivatives were confirmed to exhibit antibacterial activity.

Recent progress in the synthesis of azoles and related five‐membered ring heterocycles using silica‐supported heterogeneous catalysts

AbstractIn the last decade, silica‐supported heterogeneous catalysts have emerged as efficient green catalysts for the development of synthetic protocols of bioactive heterocycles. These catalysts possess better significant features when compared with the activities of homogeneous catalysts. Azoles are five‐membered nitrogen‐containing heterocyclic compounds that possess a wide range of medicinal properties. In this review, a summary of the recent progress on silica‐supported heterogeneous catalyzed synthetic methods of azoles and related five‐membered heterocycles is presented.

TEMPO-Mediated Selective Synthesis of Isoxazolines, 5-Hydroxy-2-isoxazolines, and Isoxazoles via Aliphatic δ-C(sp3)-H Bond Oxidation of Oximes.

Selective synthesis of three different bioactive heterocycles; isoxazolines, 5-hydroxy-2-isoxazolines and isoxazoles from the same starting material using TEMPO (2,2,6,6-Tetramethylpiperidin-1-oxyl) as a radical initiator is reported. Selectivity was achieved using different oxidants with TEMPO. The reaction goes through a 1,5-HAT (hydrogen atom transfer) process resulting in products with good yields. This strategy offers a straightforward route to three different heterocycles from oximes via radical-mediated C(sp3 )-H oxidation.

Recent Advances in Transition-Metal-Free Late-Stage C-H and N-H Arylation of Heteroarenes Using Diaryliodonium Salts.

Transition-metal-free direct arylation of C-H or N-H bonds is one of the key emerging methodologies that is currently attracting tremendous attention. Diaryliodonium salts serve as a stepping stone on the way to alternative environmentally friendly and straightforward pathways for the construction of C-C and C-heteroatom bonds. In this review, we emphasize the recent synthetic advances of late-stage C(sp2)-N and C(sp2)-C(sp2) bond-forming reactions under metal-free conditions using diaryliodonium salts as arylating reagent and its applications to the synthesis of new arylated bioactive heterocyclic compounds.

Recent Advancements in the Synthesis and Chemistry of Benzo-fused Nitrogen- and Oxygen-based Bioactive Heterocycles.

Since a variety of benzo-fused nitrogen- and oxygen-based bioactive heterocyclic moieties are present in the form of benzoxazinones, spirooxindole-based heterocyclic compounds, coumarinfused heterocyclic compounds, and 2H-indazoles, this review article briefly describes some of the major advancements and developments in the area of 1,4-benzoxazine-3-ones, 1,4-benzoxazin-2- ones, spiropyrrolidine and spiropyrrolizine-based ring compounds, coumarin-fused compounds, benzopyran- fused coumarins and a 2H-indazoles class of bioheterocycles. Thus, keeping in view the medicinal importance of these bioactive benzo-fused heterocycles, special attention has been given to their synthesis as well as medicinal/pharmaceutical properties in detail.

Efficient and Facile Synthesis of Chromenopyrano[2,3-b] pyridine Derivatives Catalyzed by Sodium Carbonate

In this research, a number of new and known chromenopyrano[2,3-b]pyridine derivatives have been prepared. Initially, according to the reported procedure, pyrano[2,3-c]chromene derivatives were synthesized by the reaction between 4-hydroxycoumarin, aromatic aldehydes and malononitrile using silica sodium carbonate (SSC) as the catalyst. Next, the prepared pyrano[2,3-c]chromenes were reacted by dimethyl acetylenedicarboxylate (DMAD) or cyclohexanone in the presence of sodium carbonate to produce chromenopyrano[2,3-b]pyridine derivatives. The presented protocol avoids the use of expensive catalysts and gives useful potentially bioactive heterocycles in excellent to high yields.

Design, synthesis, molecular modeling, and biological evaluation of novel kojic acid derivatives containing bioactive heterocycle moiety as inhibitors of tyrosinase and antibrowning agents

Tyrosinase plays an important role in melanin biosynthesis and enzymatic browning of fresh-cut fruit and vegetables. To discover potent tyrosinase inhibitors and antibrowning agents, a series of novel kojic acid derivatives containing bioactive heterocycle moiety (4a-4l) were designed and synthesized. Thereinto, 4d displayed the most potent tyrosinase inhibitory activity with IC50 of 3.23 ± 0.26 μM and behaved as a competitive inhibitor with a Ki of 1.96 μM, compared to kojic acid (IC50 = 32.23 ± 2.01 μM). Besides, copper-chelating assay, fluorescence spectrum quenching experiment, ANS-binding fluorescence quenching analysis, and molecular modeling studies indicated that 4d may inhibit tyrosinase activity by chelating with copper ions in the active site of tyrosinase. Furthermore, 4d exhibited low cytotoxic activity and significant antibrowning effects.This study suggests that these compounds may serve as lead molecules for developing novel tyrosinase inhibitors and antibrowning agents.

Recent Advances in Synthesis and Biological Assessment of Quinoline‐Oxygen Heterocycle Hybrids

AbstractThe exploration of hybrid molecules for targeting various diseases represents a highly promising approach which has showcased significant momentum worldwide, in the last two decades. Diversely substituted quinoline scaffolds present in naturally occurring bioactive compounds, signify their role in various biological processes and stimulated the research developments around it, for diverse therapeutic applications. With the ongoing search for suitable pharmacophores, the quinoline derivatives have emerged as versatile compounds possessing significant and broad spectrum of biological activities. Further, conjugation of quinoline with other bioactive heterocycles containing oxygen yielded hybrid organic frameworks with improved therapeutic profile leading to an emerging paradigm and tremendous growth in the contemporary drug discovery regime. The synthesis of these hybrid skeletons with high efficiency still remains the most strenuous task and a lot of research work is being performed in this direction. In the present article, we have reviewed the synthetic protocols leading to quinoline‐oxygen heterocycle hybrids and also highlighted the systematic and biological assessment of developed pharmacophores.

Recent Advances in Synthesis and Reactions of β-Amino-α ,β -Enones (Enaminones).

β-Amino-α,β-enones or β-enamino carbonyl compounds are versatile synthons intermediates for the construction of various bio-active heterocyclic compounds and have been established as multipurpose synthetic precursors in organic syntheses and in pharmaceutical developments. In this work, we will discuss the different synthetic routes to obtain β-amino-α,β-enones or β-enamino carbonyl compounds, their reactions, and their utility in the construction of organic frameworks and heterocyclic ring systems. Structurally, β- amino-α,β-enones are attractive intermediates that syndicate the ambident behaviours of nucleophilicity and electrophilicity of enones at the same time. β-amino-α,β-enones have been known as acceptors in both 1,2- and 1,4- additions that make them good intermediate compounds for annulation to different heterocycles.

Recent Applications of Heteropolyacids and Related Compounds in Heterocycle Synthesis. Contributions between 2010 and 2020

Over the past two decades, polyoxometalates (POM) have received considerable attention as solid catalysts, due to their unique physicochemical characteristics, since, first, they have very strong Bronsted acidity, approaching the region of a superacid, and second, they are efficient oxidizers that exhibit rapid redox transformations under fairly mild conditions. Their structural mobility is also highlighted, since they are complex molecules that can be modified by changing their structure or the elements that compose them to model their size, charge density, redox potentials, acidity, and solubility. Finally, they can be used in substoichiometric amounts and reused without an appreciable loss of catalytic activity, all of which postulate them as versatile, economic and ecological catalysts. Therefore, in 2009, we wrote a review article highlighting the great variety of organic reactions, mainly in the area of the synthesis of bioactive heterocycles in which they can be used, and this new review completes that article with the contributions made in the same area for the period 2010 to 2020. The synthesized heterocycles to be covered include pyrimidines, pyridines, pyrroles, indoles, chromenes, xanthenes, pyrans, azlactones, azoles, diazines, azepines, flavones, and formylchromones, among others.

Overview of the Biological Activities of Pyrimido[4,5-d]pyrimidines.

Over the years, the development of bioactive heterocycles has aroused the interest of the scientific community, because in general, these heterocycles are strategic in maintaining life. Research into bioactive heterocycles is associated with the development of methods of synthesis and the biological evaluation of different nuclei. In consequence, there has been a growing interest in the nucleus of fused pyrimidine, which has diversified pharmacological activities, including diuretic, antimicrobial, antifolate, tyrosine kinase, anti-inflammatory, anticancer, anthelminthic, and antiviral activities. This review focuses on describing a diverse set of structures derived from pyrimido[4,5-d]pyrimidines and contemplates the main bioactivities of these nuclei.

P-Sulfonic Acid Calix[n]arene Catalyzed Synthesis of Bioactive Heterocycles: A Review

Metal-free organocatalysts are becoming an important tool for the sustainable development of various bioactive heterocycles. On the other hand, during the last two decades, calix[n]arenes have been gaining considerable attention due to their wide range of applicability in the field of supramolecular chemistry. Recently, sulfonic acid functionalized calix[n] arenes are being employed as an efficient alternative catalyst for the synthesis of various bioactive scaffolds. In this review, we have summarized the catalytic efficiency of p-sulfonic acid calix[n]arenes for the synthesis of diverse, biologically promising scaffolds under various reaction conditions. There is no such review available in the literature showing the catalytic applicability of p-sulfonic acid calix[n]arenes. Therefore, it is strongly believed that this review will surely attract those researchers who are interested in this fascinating organocatalyst.

Review for metal and organocatalysis of heterocyclic C-H functionalization

Over the last few decades, significant efforts have been put forth towards the C−H bond group functionalization by transition-metalcatalysis and organocatalysis. Several efficient strategies to convert C-H bond to other groups C-C, C-N, C-O bonds have been implemented. The most attractive C-H bond functionalization was the C-H heterocyclic compounds activation that is practical method in organic synthesis. The new C–C, C–N and C–O bond as formed from the C-H bond activation by two diverse ways metal catalysis and/or organocatalysis. The most important is the synthesis of new bioactive heterocyclic compounds by easy and less expensive materials. In this review, we will cover most of the syntheses of heterocyclic derivatives by the functionalization of C-H bond in metal and organocatalytic reagents.

Tungsten oxides: green and sustainable heterogeneous nanocatalysts for the synthesis of bioactive heterocyclic compounds.

Tungsten oxide (WO3) as an efficient heterogeneous catalyst was prepared via a simple hydrothermal route for the synthesis of a wide range of bioactive heterocyclic compounds. The present investigation deals with the rapid and low-cost synthesis of C-3-alkylated 4-hydroxycoumarin, chromene, and xanthene derivatives. WO3 nanorods (NRs) are successfully envisaged to catalyze desired transformations, demonstrating the wide range of their potential applications in catalysis. Synthetic transformation details, smallest catalytic amounts, excellent product yields, and plausible reaction mechanisms for the formation of these heterocyclic scaffolds are elicidated. As-prepared WO3 NRs are characterized to confirm their structural, chemical, and morphological parameters by X-ray diffraction, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy measurements, respectively. We discuss the factors that govern the formation of products, and the active role of WO3 NRs, which are essential for the activation of substrates in the present study of thermal conditions. Herein, detailed synthesis and spectroscopic information of the prepared compounds are reported.

CDATA[Recent Advances in the Development of 1,2,3-Triazole-containing Derivatives as Potential Antifungal Agents and Inhibitors of Lanoster ol 14α-Demethylase.

1,2,3-Triazole, a five-membered heterocyclic nucleus, is widely recognized as a key chromophore of great value in medicinal chemistry for delivering compounds possessing innumerable biological activities, including antimicrobial, antitubercular, antidiabetic, antiviral, antitumor, antioxidants, and anti-inflammatory activities. Mainly, in the past years, diverse conjugates carrying this biologically valuable core have been reported due to their attractive fungicidal potential and potent effects on various infective targets. Hence, hybridization of 1,2,3-triazole with other antimicrobial pharmacophores appears to be a judicious strategy to develop new effective anti-fungal candidates to combat the emergence of drug-sensitive and drug-resistant infectious diseases. Thus, the current review highlights the recent advances of this promising category of 1,2,3-triazole-containing hybrids incorporating diverse varieties of bioactive heterocycles such as conozole, coumarin, imidazole, benzimidazole, pyrazole, indole, oxindole, chromene, pyrane, quinazoline, chalcone, isoflavone, carbohydrates, and amides. It underlies their inhibition behavior against a wide array of infectious fungal species during 2015-2020.