1,2,3-Triazole is an aromatic, five-membered, π-excessive heterocycle with a 6π electron ring system, comprised of three regular nitrogen atoms. 1,2,3- Triazoles possess a broad spectrum of bioactivities such as anticancer, antimicrobial, anti-inflammatory, antidiabetic, antiviral, and anti-HIV activity. Several compounds containing a 1,2,3-triazole moiety have been employed as drugs in the market. In organic synthesis, these heterocycles also play an important role as building blocks for different transformations. Furthermore, applications of 1,2,3- triazole derivatives as agrochemicals, corrosion retardants, polymers, optical brighteners, photostabilizers, pigments, and metal chelators have also well reported. Due to a wide range of applications, the synthesis of 1,2,3-triazoles has attracted tremendous research interest of chemists, and a huge number of studies on the synthesis of these heterocycles have been published over the years. In this review article, we focus on the use of organocatalysts for the synthesis of 1,2,3-triazoles. 62 studies on the synthesis of 1,2,3-triazoles have been collected and analyzed. We also try to describe reaction mechanisms as fully as possible. The study might be useful for chemists who work in heterocyclic synthesis or medicinal chemistry.
This review addresses the synthesis methodologies, chemical reactions, and biological activities of 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile and its derivatives. It was generated via the reaction of acetylacetone with cyanoacethydrazide in boiling ethanol. 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile is considered a key intermediate in the synthesis of newer pyridine derivatives by facile methods e.g., Schiff’s bases, α-aminophosphonates, α-aminohydrazones, triazolo[1,5-a]pyridines, pyrazolo[1,5-a]pyridines, bispyridones, and 1,3-thiazole derivatives. The chemical reactions are categorized based on the kind of reactants, including (1) condensation reactions involving aldehydes and ketones; (2) reactions with pyran derivatives; (3) cyanoacetylation; (4) reactions with ammonium thiocyanate; and (5) reactions with phenyl isothiocyanate. This review encapsulated several medicinal applications, including anticancer, antibacterial, antioxidant, and anti-inflammatory actions.
Heterocycles, particularly those bearing nitrogen and oxygen, hold a prominent importance in the industrial and medicinal world due to their extensive applications. Most of the top-selling drugs possess nitrogen and oxygen in them, and thus caught the attention of the majority of the scientific community. Various green methodologies have been adopted for the synthesis of these biologically important scaffolds; similarly, in this context, ionic liquids (ILs) have also been explored. In general, ionic liquids have been considered a safer and greener alternative in comparison to traditional solvents for the synthesis of various heterocycles. Thus, this manuscript in general focuses on the synthesis of ionic liquids, their classifications, unique properties, and various types of ionic liquids used for the synthesis of nitrogen and oxygen-containing heterocycles. Many reactions have been documented for exploration in the ionic liquids for the synthesis of heterocycles. Many one-pot synthesis reactions also explored ionic liquids, which also proved to increase the overall reaction yield. Towards the continuation of our previous coverage on ILs, IL-catalysed synthesis of heterocycles, we have reported the synthesis of heterocycles in 2023 with the insightful mechanistic aspects of the ionic liquids.
Abstract: Coumarin and its derivatives represent an important class of heterocyclic compounds known for their diverse pharmacological properties. Among them, 3-acetylcoumarin is a synthetically accessible derivative obtained from the naturally occurring benzopyrone scaffold, coumarin, which is widely distributed in plant sources such as Tonka beans, cinnamon, and sweet clover. Structurally, 3-acetylcoumarin consists of a coumarin core (2H-chromen-2-one) bearing an acetyl substituent at the C-3 position. This structural modification enhances the compound’s lipophilicity and chemical reactivity, potentially improving its interaction with biological targets. Coumarin derivatives have been reported to exhibit a broad spectrum of biological activities, including anti-inflammatory, antidiabetic, antioxidant, antimicrobial, anticoagulant, anticancer, analgesic, and anti- Alzheimer effects. In particular, the presence of an acetyl group at the 3-position may contribute to improved modulation of key inflammatory mediators, such as cyclooxygenase enzymes (COX-1 and COX-2), and other signalling pathways involved in inflammation and cancer progression. Owing to these promising structural and biological features, 3-acetylcoumarin has emerged as an attractive lead scaffold for the development of novel therapeutic agents. Current research efforts are therefore focused on further structural modification of the coumarin framework to enhance biological activity, selectivity, and pharmacological efficacy.
Abstract: This mini-review highlights the anticancer properties of hydroxy-substituted natural and synthetic flavonoids and their analogs. Natural and synthetic flavonoids have been reported. These compounds exhibit various biological activities, including anticancer. The role of hydroxy substituents located on ring A, B, or both rings of the flavonoid backbone has been underlined. The anticancer properties of 10 natural flavonoids are comprehensively described. The synthetic flavonoids involved in the potential treatment of leukaemia and hepatocellular carcinoma are also described.
Abstract: Nitrogen-containing heterocycles have long been recognized for their structural diversity and biological significance, making them key targets for research. These compounds occur in particular naturally derived products and exhibit substantial chemical and biological relevance. In organic chemistry, they are essential and often possess therapeutic and pharmacological properties. The ability of heterocycles containing nitrogen and oxygen to influence physicochemical properties has led to the development of chromone-fused or embedded 1,2,3-triazoles, which have become highly significant in both medical and chemical research over recent decades. Medicinal chemists have found that combining two or more pharmacophores into well-known, biologically active compounds often enhances their performance. This strategy may yield complementary biological effects and enhance the efficacy of the parent molecules. The 1,2,3-triazole moiety is a crucial pharmacophore in this class of heterocycles, and its potential for developing more potent agents with enhanced activity is highly promising. To explore novel chemical landscapes for drug-like compounds with greater structural diversity, integrating diversityoriented synthesis with 'privileged' motifs and bioorthogonal reactions, alongside advanced automation and flow technologies, could improve efficiency in drug discovery. This review highlights the role of 1,2,3- triazoles, synthesized via click chemistry, in exhibiting antimicrobial, antitubercular, antidiabetic, anticancer, anticholinesterase, and anticonvulsant activities. It also examines chromone-based 1,2,3-triazoles, which have garnered considerable attention from 2008 to 2025 due to their broad antimicrobial and anticancer potential.
Oxadiazoles are heterocyclic compounds known for their remarkable chemical stability and diverse pharmacological characteristics, making them appealing scaffolds for drug development. This review examines eco-friendly, high-yield synthetic methods-such as microwave-assisted cyclization, catalyst-free dehydrative condensation, and solvent-free grinding-that produce 1,3,4-oxadiazole derivatives with superb atom economy, often yielding over 80%. We review clinically approved medications that contain the 1,3,4-oxadiazole core (e.g., pleconaril, raltegravir, oxolamine) and point out emerging analogues showing strong anticancer, antifungal, and anticonvulsant effects in both experimental settings and in silico assessments. Structure-activity relationship studies indicate how minor changes to the heterocyclic ring can significantly affect target affinity and metabolic stability. Finally, we emphasize the importance of continuing the integration of green chemistry techniques with advanced bioactivity profiling-utilizing in vitro assays, computational modeling, and mechanistic studies-to harness the full therapeutic potential of 1,3,4-oxadiazole derivatives, thereby paving the way for a new generation of more effective, selective, and sustainable drug candidates.
In this work, we investigated the ability of pyrrolidine-appended quinoline derivatives to inhibit alpha-amylase and alpha-glucosidase, two important targets for the treatment of type 2 diabetes. Compounds 4a-c were synthesized using two bioactive pharmacophores, 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile 2 and substituted quinolines, and were subsequently characterized. Using acarbose as a standard, the compounds were evaluated for their ability to inhibit alpha-glucosidase and alpha-amylase. A detailed in silico analysis, including density functional theory (DFT) studies, molecular docking, and molecular dynamics simulations, was carried out to supplement the experimental results. According to the findings, compound 4b demonstrated encouraging in vitro inhibitory activity against alpha-glucosidase (IC50 = 41.06 +/- 1.73 & micro;g/mL) and alpha-amylase (IC50 = 22.84 +/- 0.32 & micro;g/mL), and was slightly less potent than acarbose, indicating its potential as a dual inhibitor. The compound can be further optimized and developed for clinical applications.
Asymmetric reduction by enzymatic action leads the way in green biocatalysis as a viable path toward chiral drug precursors. This article summarizes the research progress of three pivotal NADPH-dependent reductases, including amine dehydrogenases (AmDHs), imine reductases (IREDs), and ene reductases (EREDs), in asymmetric reductive amination, imine reduction, and asymmetric olefin reduction, and highlights the catalytic mechanisms, substrate scopes, stereoselectivities, as well as enzyme engineering modification strategies for the above key reactions. Advances in directed evolution, rational design, and system optimization (including cofactor regeneration and photoenzyme catalysis) have significantly alleviated traditional bottlenecks (e.g., low enzyme activity, coenzyme instability, and poor stereoselectivity), yielding biocatalysts with enhanced stability and performance and greater industrial applicability. In addition, this article summarizes successful applications of these enzymes in the synthesis of key chiral building blocks for various drugs. It discusses their future directions for development in sustainable chemical synthesis and industrial scale-up.
Abstract: The genus Symplocos (the family Symplocaceae) has long been used in traditional medicine for treating inflammatory, metabolic, and hepatic disorders. Recent pharmacological evidence supports these uses, yet no integrated evaluation of its chemistry, biological mechanisms, and Structure-activity Relationships (SAR) has been conducted. The current study provides an insightful review of the structural diversity, pharmacological actions, and SAR of Symplocos species, emphasizing their therapeutic importance and potential involvement in integrative medicine. Information was methodologically gathered from the English scientific databases, including Scopus, Web of Science, Google Scholar, and ScienceDirect, up to September 2025. The most significant keyword that was utilized alone or in combination to find references was “Symplocos”. A total of 236 compounds have been summarized, the majority of which are triterpenoids, triterpenoid saponins, phenolics, flavonoids, and lignans. Numerous in vitro and in vivo pharmacological results were documented, including cytotoxic, antioxidant, anti-inflammatory, antidiabetic, antinociceptive, antidepressant, hepatoprotective, renoprotective, and reproductive hormonal activities. Mechanistically, these actions involved the regulation of the PI3K/Akt, MAPK, and NF-κB pathways, the enhancement of GSH, SOD, and CAT activities, and the RORγt-Th17 inhibition in metabolic and autoimmune models. From the SAR analysis, glycosylation and other substitution patterns remarkably affected bioactivity and selectivity. Symplocos species are a rich reservoir of bioactive molecules with clearly defined mechanistic and structural determinants. Their proven pharmacological properties provide a scientific basis for the development of mechanism-based natural therapies.
Abstract: Nicotinamide-containing heterocycles are gaining increasing interest in medicinal chemistry due to their potential applications in cancer drug development. Their structural characteristics significantly influence both biological activity and therapeutic efficacy. The purpose of this review is to summarize recent advancements in the synthesis of nicotinamide derivatives and to evaluate their reported anticancer activities against various cancer types. Different synthesis methods for nicotinamide-based compounds were compiled and described, together with data on their anticancer efficacy and mechanisms of action, by analysing pertinent literature. Various chemical methods have been employed to synthesize a wide range of nicotinamide derivatives. These compounds exhibit significant cytotoxicity against breast, lung, colon, and rectal cancer cell lines. Documented mechanisms of action include the induction of apoptosis and enzyme inhibition. Due to its structural versatility, the nicotinamide moiety serves as a valuable scaffold for the development of anticancer drugs. Nicotinamide derivatives are a promising family of compounds with strong anticancer potential. Their usefulness in creating tailored cancer treatments is highlighted by their effective synthetic accessibility and proven biological activity. This review encourages more research on nicotinamide scaffolds in the search for anticancer drugs.
Cross-coupling reactions enable the formation of carbon-carbon and carbon-heteroatom bonds between organometallic nucleophiles and electrophiles, serving as a keystone of modern synthetic chemistry. These useful transformations, forged in the 20th century, have evolved to feature Pd-catalyzed reactions that have predominated owing to their mild conditions and broad substrate scope. Pd-catalyzed cross-coupling reactions, such as Stille, Negishi, Suzuki-Miyaura, and Sonogashira, have become indispensable tools for generating C-C and C-X bonds. These transformations play a pivotal role in developing advanced materials, pharmaceuticals, and agrochemicals. Furthermore, extensive research has led to the development of cross-coupling reactions to synthesize biologically and pharmaceutically relevant organic molecules. Additionally, these reactions have resulted in significant progress in various underdeveloped areas of synthetic organic chemistry. Several catalytic systems and ligands have been developed to enable C-C bond-forming transformations via cross-coupling methodologies. This review delineates recent advancements from 2020 onward, categorizing Pd-catalyzed C-C cross-coupling reactions into five principal variants- Suzuki-Miyaura, Heck-Mizoroki, Sonogashira, Negishi, and Stille- based on their mechanistic and organometallic coupling partners.
The Strecker reaction enables the straightforward, one-step synthesis of α-amino nitriles, which serve as valuable building blocks for a wide range of important products, including α-amino acids and their derivatives. α-Amino acids play a fundamental role in biological systems, and both natural and synthetic α-amino acids are extensively employed in medicinal chemistry. Among the available strategies, the asymmetric Strecker reaction remains the most widely used approach for synthesizing α-amino acids. Over the past few decades, asymmetric versions of this reaction have been intensively explored, encompassing diastereoselective reactions-particularly in the total synthesis of natural and bioactive compounds-as well as enantioselective metal- and organocatalyzed cyanations of imines. The diversity of catalysts employed in these enantioselective transformations highlights the considerable potential for further developments in the near future. In addition to the traditionally used, but highly toxic, HCN and TMSCN, greener and more cost-effective cyanide sources such as KCN, NaCN, acetone cyanohydrin, and ethyl cyanoformate are gaining attention for industrial applications. While metal-promoted enantioselective cyanations of imines are well-established, the more economical and environmentally friendly organocatalytic approaches are expected to be increasingly preferred, in line with the principles of green chemistry. Today, the asymmetric Strecker reaction continues to represent the simplest and most efficient methodology for synthesizing chiral α-amino acids and their derivatives. This review provides an update on the field of asymmetric Strecker reactions since 2014. It is organized into four sections, covering diastereoselective Strecker reactions, organocatalyzed enantioselective Strecker reactions, metal/boron-catalyzed enantioselective Strecker reactions, and asymmetric Strecker reactions facilitated by crystallization processes.
Abstract: Asymmetric intramolecular haloamination of alkenes is a crucial transformation in modern organic and medicinal chemistry. This strategy is able to introduce both halogen and nitrogen atoms simultaneously in a highly efficient and stereospecific manner. Chiral centers and nitrogen-containing rings are allowed to establish concurrently within a molecular framework. This building process is generally initiated by using an appropriate catalytic system that can activate the halogenating reagent. Then, the activated halogen species and the alkene substrate interact to generate a key intermediate that is most typically a halonium ion. Subsequently, a nitrogencontaining group such as an amine, amide, or sulfonamide undergoes an internal nucleophilic attack that leads to the formation of various nitrogen-containing rings. This article provides a few comments on the different asymmetric intramolecular haloamination systems reported in recent literature. This article comments on several typical asymmetric intramolecular haloamination of alkenes systems, and emphasizes the advantages and disadvantages of the stereocontrol mechanisms, expansion of substrate scope, and optimization of reaction conditions. Looking forward, this article outlines corresponding research directions to address these limitations, suggesting potential methodological approaches.
Pyrimidines are nitrogen-containing singular heterocycles renowned for having a broad spectrum of therapeutic applications in anticancer and antiviral drug development. Many anticancer drugs that are sold commercially contain pyrimidine moieties. Based on these findings, the synthesis of several possible pyrimidine derivatives with anticancer activity, reported between 2018 and 2023, is thoroughly explained in this review. Further, this review highlights the in vitro and molecular docking studies of several malignancies. Recent advances in the synthesis of pyrimidine analogs, along with their anticancer activity reported in this review, make this heterocyclic moiety an attractive scaffold for discovering newer anticancer drugs.
Abstract: Breast cancer is still the most prevalent cause of cancer-related death in women, and resistance and relapse frequently restrict the effectiveness of current therapy. Thiazole derivatives, a well-known class of heterocyclic compounds containing sulphur, have shown great promise as adaptable scaffolds with anticancer properties. Their molecular functions in targeting various breast cancer receptors and signaling cascades, as well as their structural variety and synthesis techniques, are highlighted in this study. While thiazole-based drugs effectively inhibit HER2, EGFR, VEGFR, CDK4/6, and aromatase enzymes, they also have considerable affinity for estrogen, progesterone, and androgen receptors. In addition, derivatives have demonstrated multitarget inhibitory qualities, specifically against the PARP enzymes and the PI3K/AKT/mTOR axis, which can help overcome treatment resistance. Numerous thiazole hybrids have been shown in preclinical research to cause reduced angiogenesis, cell cycle arrest, and apoptosis in breast cancer cell lines, including aggressive subtypes like triple-negative breast cancer. Despite the difficulties associated with systemic toxicity and pharmacokinetic variability, prodrug design, nanocarriers, and antibody-drug conjugates are promising developments. The design of next-generation, multitargeted therapies to increase the effectiveness and survival rates of patients with breast cancer is greatly aided by the collective thiazole derivatives.
A naturally occurring xanthine derivative, theobromine has garnered considerable attention due to its broad range of biological activities and potential medical applications. In recent decades, theobromine chemistry has garnered considerable attention due to its numerous biological applications. The present study reports on several methods for synthesizing theobromine derivatives and their anticancer activity. Numerous biological properties, including antioxidant, anti-tumor, anti-inflammatory, bronchodilator, cardiovascular, and antibacterial properties, are provided by theobromine and its derivatives, which are members of the nitrogen-containing heterocycle family. Our findings highlight the therapeutic potential of theobromine as an anticancer agent. In addition to compiling the literature on theobromine's anticancer activity as reported by researchers, this study aims to highlight the most recent advancements regarding theobromine and provide a comprehensive understanding of theobromine, thereby opening the door for future research and therapeutic improvements.
2-Aminobenzothiazole represents a versatile class of heterocyclic compounds that is composed of a fused benzene ring and a thiazole ring. In recent years, benzothiazole derivatives have garnered considerable attention for research and development due to their broad spectrum of pharmacological properties. Owing to their strong pharmacological activity and wide range of applications, synthetically accessible and adaptable 2- aminobenzothiazole scaffolds are very intriguing in the fields of biology and synthetic organic chemistry. Benzothiazole moiety-containing analogs possess significant antimicrobial, antiviral, anti-inflammatory, antidiabetic, anticancer, antimalarial, antitubercular, anticonvulsant, antiasthmatic, diuretic, analgesic, and anthelmintic activities. Research on the pharmaceutical properties of benzothiazole derivatives remains a fascinating area with potential for discovering novel drugs or treatments. The promising medicinal properties of benzothiazoles and their derivatives have prompted medicinal chemists to develop numerous new therapeutic agents, thereby driving the development of efficient and innovative synthetic approaches. This review focuses on the numerous methods of synthesis and reactions of 2-aminobenzothiazoles and their derivatives that have been utilized over the period 2010-2025, to encourage further research and innovation in the development of novel compounds with a range of applications in drug discovery and other fields.
