Recent efforts in the development of glycoconjugate vaccine and available treatment for tuberculosis.

Tuberculosis (TB) continues to pose a grave threat to global health, despite relentless eradication efforts. In 1882, Robert Koch discovered that Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing tuberculosis. It is a fact that tuberculosis has claimed the lives of more than one billion people in the last few decades. It is imperative that we must take immediate and effective action to increase resources for TB research and treatment. Effective TB treatments demand an extensive investment of both time and finances, often requiring 6-9 months of rigorous antibiotic therapy. The most efficient way to control tuberculosis is by receiving a childhood Bacillus Calmette-Guérin (BCG) vaccination. Despite years of research on vaccine development, we still do not have any new approved vaccine for tuberculosis, except BCG, which is partially effective in young children. This review discusses briefly the available treatment for tuberculosis and remarkable advancements in glycoconjugate-based TB vaccine developments in recent years (2013-2024) and offers valuable direction for future research priorities.

iPSC-derived hindbrain organoids to evaluate escitalopram oxalate treatment responses targeting neuropsychiatric symptoms in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia, and the gradual deterioration of brain function eventually leads to death. Almost all AD patients suffer from neuropsychiatric symptoms (NPS), the emergence of which correlates with dysfunctional serotonergic systems. Our aim is to generate hindbrain organoids containing serotonergic neurons using human induced Pluripotent Stem Cells (iPSCs). Work presented here is laying the groundwork for the application of hindbrain organoids to evaluate individual differences in disease progression, NPS development, and pharmacological treatment response. Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 3), an AD patient without NPS (n = 1), and AD patients with NPS (n = 2) were reprogrammed into iPSCs and subsequently differentiated into hindbrain organoids. The presence of serotonergic neurons was confirmed by quantitative reverse transcription PCR, flow cytometry, immunocytochemistry, and detection of released serotonin (5-HT). We successfully reprogrammed PBMCs into 6 iPSC lines, and subsequently generated hindbrain organoids from 6 individuals to study inter-patient variability using a precision medicine approach. To assess patient-specific treatment effects, organoids were treated with different concentrations of escitalopram oxalate, commonly prescribed for NPS. Changes in 5-HT levels before and after treatment with escitalopram were dose-dependent and variable across patients. Organoids from different people responded differently to the application of escitalopram in vitro. We propose that this 3D platform might be effectively used for drug screening purposes to predict patients with NPS most likely to respond to treatment in vivo and to understand the heterogeneity of treatment responses.

Efficient synthesis of indole-chalcones based glycohybrids and their anticancer activity.

Indole based glycosides belong to the class of pharmacologically active molecules and found in diverse natural compounds. Herein, we report the synthesis of 1,2,3-triazole bridged chirally enriched diverse indole-chalcones based glycohybrids. Three series of glycohybrids were designed and efficiently synthesized using d-glucose, d-galactose and d-mannose derived 1-azido glycosides. The reactions sequence involved were, the synthesis of indole derived chalcones which were formed via Claisen-Schmidt condensation reaction and subsequently N-propargylation which leads to the production of N-propargylated indole-chalcones. The N-propargylated indole-chalcones get transformed into 1,2,3-triazole bridged indole-chalcone based glycohybrids by reacting with 1-azido sugar glycosides under click-chemistry reaction conditions. Further, the biological activity of synthesized glycohybrids (n = 27) was assessed in-vitro against MDA-MB231, MCF-7, MDA-MB453 cancer, and MCF-10A normal cell lines. The selected compounds showed potent anti-oncogenic properties against MCF-7 and MDA-MB231 breast cancer cell line with IC50 values of 1.05 µM and 11.40 µM respectively, with very good selectivity index (SI > 161). The active compounds show better binding affinity as compared to co-crystallized inhibitor 1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) with HCK (PTKs) proteins in molecular docking studies.

Applications of Pyrrole and Pyridine-based Heterocycles in Cancer Diagnosis and Treatment.

BACKGROUND: The escalation of cancer worldwide is one of the major causes of economy burden and loss of human resources. According to the American Cancer Society, there will be 1,958,310 new cancer cases and 609,820 projected cancer deaths in 2023 in the United States. It is projected that by 2040, the burden of global cancer is expected to rise to 29.5 million per year, causing a death toll of 16.4 million. The hemostasis regulation by cellular protein synthesis and their targeted degradation is required for normal cell growth. The imbalance in hemostasis causes unbridled growth in cells and results in cancer. The DNA of cells needs to be targeted by chemotherapeutic agents for cancer treatment, but at the same time, their efficacy and toxicity also need to be considered for successful treatment. OBJECTIVE: The objective of this study is to review the published work on pyrrole and pyridine, which have been prominent in the diagnosis and possess anticancer activity, to obtain some novel lead molecules of improved cancer therapeutic. METHODS: A literature search was carried out using different search engines, like Sci-finder, Elsevier, ScienceDirect, RSC etc., for small molecules based on pyrrole and pyridine helpful in diagnosis and inducing apoptosis in cancer cells. The research findings on the application of these compounds from 2018-2023 were reviewed on a variety of cell lines, such as breast cancer, liver cancer, epithelial cancer, etc. Results: In this review, the published small molecules, pyrrole and pyridine and their derivatives, which have roles in the diagnosis and treatment of cancers, were discussed to provide some insight into the structural features responsible for diagnosis and treatment. The analogues with the chromeno-furo-pyridine skeleton showed the highest anticancer activity against breast cancer. The compound 5-amino-N-(1-(pyridin-4- yl)ethylidene)-1H-pyrazole-4-carbohydrazides was highly potent against HEPG2 cancer cell. Redaporfin is used for the treatment of cholangiocarcinoma, biliary tract cancer, cisplatin-resistant head and neck squamous cell carcinoma, and pigmentation melanoma, and it is in clinical trials for phase II. These structural features present a high potential for designing novel anticancer agents for diagnosis and drug development. CONCLUSION: Therefore, the N- and C-substituted pyrrole and pyridine-based novel privileged small Nheterocyclic scaffolds are potential molecules used in the diagnosis and treatment of cancer. This review discusses the reports on the synthesis of such molecules during 2018-2023. The review mainly discusses various diagnostic techniques for cancer, which employ pyrrole and pyridine heterocyclic scaffolds. Furthermore, the anticancer activity of N- and C-substituted pyrrole and pyridine-based scaffolds has been described, which works against different cancer cell lines, such as MCF-7, A549, A2780, HepG2, MDA-MB-231, K562, HT- 29, Caco-2 cells, Hela, Huh-7, WSU-DLCL2, HCT-116, HBL-100, H23, HCC827, SKOV3, etc. This review will help the researchers to obtain a critical insight into the structural aspects of pyrrole and pyridine-based scaffolds useful in cancer diagnosis as well as treatment and design pathways to develop novel drugs in the future.

Synthesis of Chirally Enriched Pyrazolylpyrimidinone-Based Glycohybrids via Annulation of Glycals with 2-Hydrazineylpyrimidin-4(3H)-ones.

A new strategy for synthesizing chirally enriched pyrazolylpyrimidinone-based glycohybrids has been achieved, employing an annulation approach in ethanol without any additives or catalysts under microwave conditions. The designed compounds were obtained within a short reaction time (5 min). This method offers several advantages, including mild reaction conditions, a green solvent, and a metal-free approach. Furthermore, the protocol demonstrated a broad substrate scope, successfully incorporating various functional groups with stereochemical diversity and furnishing chirally enriched molecules.

Recent developments on the synthesis of biologically active glycohybrids.

The exploration of hybridization emerges as a potent tool in advancing drug discovery research, with a significant emphasis on carbohydrate-containing hybrid scaffolds. Evidence indicates that linking carbohydrate molecules to privileged bioactive scaffolds enhances the bioactivity of drug molecules. This synergy results in a diverse range of activities, making carbohydrate scaffolds pivotal for synthesizing compound libraries with significant functional and structural diversity. Beyond their synthesis utility, these scaffolds offer applications in screening bioactive molecules, presenting alternative avenues for drug development. This comprehensive review spanning 2015 to 2023 focuses on synthesized glycohybrid molecules, revealing their bioactivity in areas such as anti-microbial, anti-cancer, anti-diabetic, anti-inflammatory activities, enzyme inhibition and pesticides. Numerous novel glycohybrids surpass positive control drugs in biological activity. This focused study not only highlights the diverse bioactivities of glycohybrids but also underscores their promising role in innovative drug development strategies.

Synthesis of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as anticancer agents and their in silico docking studies.

In the pursuit of novel therapeutic agents, we present a comprehensive study on the design, synthesis, and evaluation of a diverse library of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones, employing a microwave-assisted synthetic approach via 'click chemistry'. This methodology offers efficient and accelerated access to the glycohybrids, showcasing improved reaction conditions that yield high-quality products. In this research endeavor, we have successfully synthesized a series of twenty-seven triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones. Our investigation extends beyond synthetic endeavors to explore the potential therapeutic relevance of these compounds. We subjected them to rigorous in vitro screening against prominent breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB453. Among the library of compounds synthesized, (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((5-(4-methoxyphenyl)-7-oxopyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerged as a potent compound, exhibiting remarkable anti-cancer activity with an IC50 value of 27.66 µM against the MDA-MB231 cell line. Additionally, (2S,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((7-oxo-5-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate displayed notable inhibitory potential against the MCF-7 cell line, with an IC50 value of 4.93 µM. Furthermore, in silico docking analysis was performed to validate our experimental findings. These findings underscore the promise of our triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as potential anti-cancer agents. This research not only enriches the field of glycohybrid synthesis but also contributes valuable insights into the development of novel anti-cancer therapeutics.

Copper-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine based triazole-linked glycohybrids: mechanistic insights and bio-applications.

Hybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure-activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration.

Generation and Characterization of a Human-Derived and Induced Pluripotent Stem Cell (iPSC) Line from an Alzheimer's Disease Patient with Neuropsychiatric Symptoms.

Agitation is one of the most eminent characteristics of neuropsychiatric symptoms (NPS) affecting people living with Alzheimer's and Dementia and has serious consequences for patients and caregivers. The current consensus is that agitation results, in part, from the disruption of ascending monoamine regulators of cortical circuits, especially the loss of serotonergic activity. It is believed that the first line of treatment for these conditions is selective serotonin reuptake inhibitors (SSRIs), but these are effective in only about 40% of patients. Person-specific biomarkers, for example, ones based on in vitro iPSC-derived models of serotonin activity, which predict who with Agitation responds to an SSRI, are a major clinical priority. Here, we report the generation of human-induced pluripotent stem cells (iPSCs) from a 74-year-old AD patient, the homozygous APOE ε4/ε4 carrier, who developed Agitation. His iPSCs were reprogrammed from peripheral blood mononuclear cells (PBMCs) using the transient expression of pluripotency genes. These display typical iPSC characteristics that are karyotypically normal and attain the capacity to differentiate into three germ layers. The newly patient-derived iPSC line offers a unique resource to investigate the underlying mechanisms associated with neuropsychiatric symptom progression in AD.

Recent developments on microwave-assisted organic synthesis of nitrogen- and oxygen-containing preferred heterocyclic scaffolds.

In recent decades, the utilization of microwave energy has experienced an extraordinary surge, leading to the introduction of innovative and revolutionary applications across various fields of chemistry such as medicinal chemistry, materials science, organic synthesis and heterocyclic chemistry. Herein, we provide a comprehensive literature review on the microwave-assisted organic synthesis of selected heterocycles. We highlight the use of microwave irradiation as an effective method for constructing a diverse range of molecules with high yield and selectivity. We also emphasize the impact of microwave irradiation on the efficient synthesis of N- and O-containing heterocycles that possess bioactive properties, such as anti-cancer, anti-proliferative, and anti-tumor activities. Specific attention is given to the efficient synthesis of pyrazolopyrimidines-, coumarin-, quinoline-, and isatin-based scaffolds, which have been extensively studied for their potential in drug discovery. The article provides valuable insights into the recent synthetic protocols and trends for the development of new drugs using heterocyclic molecules.

Recent advancement of nanomedicine-based targeted delivery for cervical cancer treatment.

Cervical cancer is a huge worldwide health burden, impacting women in impoverished nations in particular. Traditional therapeutic approaches, such as surgery, radiation therapy, and chemotherapy, frequently result in systemic toxicity and ineffectiveness. Nanomedicine has emerged as a viable strategy for targeted delivery of therapeutic drugs to cancer cells while decreasing off-target effects and increasing treatment success in recent years. Nanomedicine for cervical cancer introduces several novel aspects that distinguish it from previous treatment options such as tailored delivery system, precision targeting, combination therapies, real-time monitoring and diverse nanocarriers to overcome the limitations of one another. This abstract presents recent advances in nanomedicine-based tailored delivery systems for the treatment of cervical cancer. Liposomes, polymeric nanoparticles, dendrimers, and carbon nanotubes have all been intensively studied for their ability to transport chemotherapeutic medicines, nucleic acids, and imaging agents to cervical cancer cells. Because of the way these nanocarriers are designed, they may cross biological barriers and preferentially aggregate at the tumor site, boosting medicine concentration and lowering negative effects on healthy tissues. Surface modification of nanocarriers with targeting ligands like antibodies, peptides, or aptamers improves specificity for cancer cells by identifying overexpressed receptors or antigens on the tumor surface. Furthermore, nanomedicine-based techniques have made it possible to co-deliver numerous therapeutic drugs, allowing for synergistic effects and overcoming drug resistance. In preclinical and clinical investigations, combination treatments comprising chemotherapeutic medicines, gene therapy, immunotherapy, and photodynamic therapy have showed encouraging results, opening up new avenues for individualized and multimodal treatment regimens. Furthermore, the inclusion of contrast agents and imaging probes into nanocarrier systems has enabled real-time monitoring and imaging of treatment response. This enables the assessment of therapy efficacy, the early diagnosis of recurrence, and the optimization of treatment regimens.

Reinvestigation of SnCl4 catalyzed efficient synthesis of 2,3-unsaturated glycopyranosides.

The Ferrier rearrangement is a powerful tool to prepare 2,3-unsaturated glycopyranosides. We have reinvestigated SnCl4 catalyzed Ferrier rearrangements through direct allylic substitution of the hydroxyl group at the C-3 position of glycals, resulting in the formation of stereoselective 2,3-unsaturated glycosides at 0 °C. The catalytic amount of SnCl4 (0.1 equiv.) was successfully used to promote this transformation on 3,4,6-tri-O-acetyl-D-glucal, 3,4,6-tri-O-acetyl-D-galactal and 3,4-di-O-acetyl-D-arabinal using various nucleophiles viz alcohols, azide and thiols to form a variety of 2,3-unsaturated glycopyranosides (pseudoglycals). This straightforward process is notable for its strong anomeric selectivity, excellent yields and shorter reaction time.

Recent progress in the synthesis of natural product inspired bioactive glycohybrids.

Carbohydrates are a basic structural component that are indispensable to all cellular processes. In addition to being employed as chiral starting materials in the synthesis of a variety of natural products, carbohydrates are recognized as naturally occurring molecules having an enormous variety of functional, stereochemical, and structural properties. The understanding and biological roles of carbohydrate derived molecules can be greatly improved by selectively synthesizing functional carbohydrates through incorporating them with privileged scaffolds. For a deeper understanding of their roles and the development of functional materials based on sugar, it is crucial to develop new techniques for efficiently synthesizing, functionalizing, and modifying carbohydrates. Glycohybrids have a wide range of structural and functional characteristics along with protein-carbohydrate interactions that are crucial to mammalian biology and a number of disease states. This review, consisting the literature from January 2017 to July 2023 and provide an overview of recent developments in the chemical synthesis of glycohybrids based on natural product scaffolds of coumarin, quinolone, naphthalene diimide, indole, isatin, naphthoquinone, imidazole and pyrimidine. The biological activity of active glycohybrids are discussed in this review.

Electro-organic synthesis of isatins and hydrazones through C-N cross-coupling and C(sp2)-H/C(sp3)-H functionalization.

An efficient and unique approach to synthesize isatin (indole-2,3-dione) from 2-aminoacetophenone under electrochemical conditions supported by I2-DMSO through C-N cross-coupling and C(sp2)-H/C(sp3)-H functionalization is presented. This synthetic method spans a wide range of substituted 2-aminoacetophenone substrates. The use of iodine as a promoter and shorter reaction times produced good to very good yields of isatin derivatives, which is a significant improvement over the reaction in a batch process. Further, hydrazones of isatin were synthesized by using hydrazine hydrate which produces electrochemically active molecules, namely isatin-hydrazones. The hydrazones of acetophenone were also obtained using the same reaction protocol. Additionally, the effect of increasing scan rate studied using cyclic voltammetry shows that the process followed a diffusion-controlled mechanism.

Excitatory Neurons Derived from Human-Induced Pluripotent Stem Cells Show Transcriptomic Differences in Alzheimer's Patients from Controls.

The recent advances in creating pluripotent stem cells from somatic cells and differentiating them into a variety of cell types is allowing us to study them without the caveats associated with disease-related changes. We generated induced Pluripotent Stem Cells (iPSCs) from eight Alzheimer's disease (AD) patients and six controls and used lentiviral delivery to differentiate them into excitatory glutamatergic neurons. We then performed RNA sequencing on these neurons and compared the Alzheimer's and control transcriptomes. We found that 621 genes show differences in expression levels at adjusted p < 0.05 between the case and control derived neurons. These genes show significant overlap and directional concordance with genes reported from a single-cell transcriptome study of AD patients; they include five genes implicated in AD from genome-wide association studies and they appear to be part of a larger functional network as indicated by an excess of interactions between them observed in the protein-protein interaction database STRING. Exploratory analysis with Uniform Manifold Approximation and Projection (UMAP) suggests distinct clusters of patients, based on gene expression, who may be clinically different. Our research outcomes will enable the precise identification of distinct biological subtypes among individuals with Alzheimer's disease, facilitating the implementation of tailored precision medicine strategies.

Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents.

Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper.

Recent advances in the synthesis of new benzothiazole based anti-tubercular compounds.

This review highlights the recent synthetic developments of benzothiazole based anti-tubercular compounds and their in vitro and in vivo activity. The inhibitory concentrations of the newly synthesized molecules were compared with the standard reference drugs. The better inhibition potency was found in new benzothiazole derivatives against M. tuberculosis. Synthesis of benzothiazole derivatives was achieved through various synthetic pathways including diazo-coupling, Knoevenagel condensation, Biginelli reaction, molecular hybridization techniques, microwave irradiation, one-pot multicomponent reactions etc. Other than recent synthetic developments, mechanism of resistance of anti-TB drugs is also incorporated in this review. Structure activity relationships of the new benzothiazole derivatives along with the molecular docking studies of selected compounds have been discussed against the target DprE1 in search of a potent inhibitor with enhanced anti-tubercular activity.

Lipid Profiling in Alzheimer's Disease.

The human brain is the organ with the most lipids after adipose tissues. The rich heterogeneity of the neural lipidome is being actively investigated with the aim of shedding new light into the physiological and pathological roles these compounds play in the brain. This is particularly important for the study of increasingly common neurodegenerative pathologies, such as Alzheimer's disease (AD), whose underlying mechanisms are still insufficiently understood and for which there is no cure. The present text dives into the current knowledge of the lipid composition of the brain, with a particular focus on the application of lipid profiling to AD research.

Metal free synthesis of 2,3-dideoxy-α, ß-unsaturated carbohydrate enals (Perlin aldehydes).

A metal free synthesis of enantiopure 2,3-dideoxy-α, ß-unsaturated carbohydrate enals (Perlin aldehydes), in CH3CN-0.02 N H2SO4 in water (1:1, v/v) with 0.5 equivalent additives (4-hydroxy-6-methyl-2-pyrone or 4-amino coumarin), has been reported. This efficient protocol works well for the acetylated glycals (glucal, galactal and arabinal) and afforded Perlin aldehydes and hemiacetals in acceptable to good yields. Whereas, benzylated glycals furnished respective Perlin aldehydes, hemiacetals and the 2-deoxy derivatives, under similar reaction conditions. The products yields were significantly reduced when the additives were removed from the reaction mixture, indicating that they constitute an essential component of this approach. Further the use of 0.02 N H2SO4 in water: acetonitrile (1:1, v/v) solvent system is essential for the formation of Perlin aldehydes. The similar reactions under neutral reaction conditions (CH3CN:H2O, 1:1, v/v) with additives, afforded the hemiacetals as major product. This methodology is a metal free approach to Perlin aldehyde synthesis and therefore having additional benefit of its use in preparation of bioactive drug molecules, where metal toxicity is the major concern.

Electro-organic green synthesis of dicyano-2-(2-oxoindolin-3-ylidene) malononitriles using molecular iodine as catalyst.

The first electrochemical molecular iodine promoted, domino reactions for the green synthesis of biologically relevant dicyano 2-(2-oxoindolin-3-ylidene) malononitriles (11 examples, up to 94% yield) from readily available isatin derivatives, malononitrile, and iodine at room temperature have been presented. This synthesis method showed tolerance towards various EDG and EWG and was completed in a short reaction time at the constant low current density of 5 mA cm-2 in the low redox potential range of -0.14 to 0.07 V. The present study exhibited by-product-free formation, easy operation, and product isolation. In particular the formation of a C[double bond, length as m-dash]C bond was observed at room temperature with a high atom economy. Furthermore, in the present study, the electrochemical behavior of dicyano 2-(2-oxoindolin-3-ylidene) malononitrile derivatives using a cyclic voltammetry (CV) technique in 0.1 M NaClO4 in acetonitrile solution was studied. All the chosen substituted isatin exhibited well-defined diffusion-controlled quasi-reversible redox peaks except 5-substituted derivatives. This synthesis could serve as an alternative strategy to synthesize other biologically important oxoindolin-3-ylidene malononitrile derivatives.