Single-cell transcriptomics reveals the intra-tumoral heterogeneity and SQSTM1/P62 and Wnt/ß-catenin mediated epithelial to mesenchymal transition and stemness of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by the complex tumor microenvironment (TME) consisting of an abundance of mesenchymal stem cells (MSCs), which is known to facilitate epithelial-to-mesenchymal transition (EMT). The development of single-cell genomics is a powerful method for defining the intricate genetic landscapes of malignancies. In this study, we have employed single-cell RNA sequencing (scRNA-seq) to dissect the intra-tumoral heterogeneity and analyze the single-cell transcriptomic landscape to detect rare consequential cell subpopulations of significance. The scRNA-seq analysis of TNBC and Normal patient derived samples revealed that EMT markers and transcription factors were most upregulated in MSC population. Further, exploration of gene expression analysis among TNBC and Normal patient-derived MSCs ascertained the role of SQSTM1/P62 and Wnt/ß-catenin in TNBC progression. Wnt/ß-catenin and Wnt/PCP signaling pathways are prominent contributors of EMT, stemness, and cancer stem cell (CSC) properties of TNBC. SQSTM1/P62 cooperates with the components of the Wnt/PCP signaling pathway and is critically involved at the interface of autophagy and EMT. Moreover, siRNA targeting SQSTM1/P62 and inhibitor of Wnt/ß-catenin (FH535) in conjunction was used to explore molecular modification of EMT and stemness markers. Although SQSTM1/P62 is not crucial for cell survival, cytotoxicity assay revealed synergistic interaction between the siRNA/inhibitor. Modulation of these important pathways helped in reduction of expression of genes and proteins contributing to CSC properties. Gene and protein expression analysis revealed the induction of EMT to MET. Moreover, co-treatment resulted in inactivation of non-canonical Wnt VANGL2-JNK signaling axis. The synergistic impact of inhibition of SQSTM1/P62 and Wnt/ß-catenin signaling facilitates the development of a potential therapeutic regimen for TNBC.

Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells.

Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.

Parametric Frequency Divider Based Ising Machines.

We report on a new class of Ising machines (IMs) that rely on coupled parametric frequency dividers (PFDs) as macroscopic artificial spins. Unlike the IM counterparts based on subharmonic-injection locking (SHIL), PFD IMs do not require strong injected continuous-wave signals or applied dc voltages. Therefore, they show a significantly lower power consumption per spin compared to SHIL-based IMs, making it feasible to accurately solve large-scale combinatorial optimization problems that are hard or even impossible to solve by using the current von Neumann computing architectures. Furthermore, using high quality factor resonators in the PFD design makes PFD IMs able to exhibit a nanowatt-level power per spin. Also, it remarkably allows a speedup of the phase synchronization among the PFDs, resulting in shorter time to solution and lower energy to solution despite the resonators' longer relaxation time. As a proof of concept, a 4-node PFD IM has been demonstrated. This IM correctly solves a set of Max-Cut problems while consuming just 600 nanowatts per spin. This power consumption is 2 orders of magnitude lower than the power per spin of state-of-the-art SHIL-based IMs operating at the same frequency.

L-Proline-catalysed synthesis of chromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione and an anti-proliferative study.

The reactivity of 4-hydroxy-2H-chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3-b]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.

Wafer-scale heterogeneous integration of thin film lithium niobate on silicon-nitride photonic integrated circuits with low loss bonding interfaces.

Silicon nitride (Si3N4) is a versatile waveguide material platform for CMOS foundry-based photonic integrated circuits (PICs) with low loss and high-power handling. The range of applications enabled by this platform is significantly expanded with the addition of a material with large electro-optic and nonlinear coefficients such as lithium niobate. This work examines the heterogeneous integration of thin-film lithium-niobate (TFLN) on silicon-nitride PICs. Bonding approaches are evaluated based on the interface used (SiO2, Al2O3 and direct) to form hybrid waveguide structures. We demonstrate low losses in chip-scale bonded ring resonators of 0.4 dB/cm (intrinsic Q = 8.19 × 105). In addition, we are able to scale the process to demonstrate bonding of full 100-mm TFLN wafers to 200-mm Si3N4 PIC wafers with high layer transfer yield. This will enable future integration with foundry processing and process design kits (PDKs) for applications such as integrated microwave photonics and quantum photonics.

Understanding Deformation and Breakup Tendency of Shear-Thinning Viscoelastic Drops in Constricted Microchannels.

The study of drop deformation in response to various stresses has long piqued the interest of several academics. The deformation behavior of cells, drug carriers, and even drug particles moving via microcapillaries inside the human body can be modeled using a viscoelastic drop model. A drop breakup study can also provide better design guidance for nanocarriers that can deliver on-demand burst drug releases at specific cancer sites. Thus, we attempted to investigate the deformation and breakup of a shear-thinning finitely extensible nonlinear elastic-peterlin (FENE-P) drop moving through the constricted microchannel. The computational simulation suggested that drop deformation and breakup can be manipulated by varying of parameters like channel confinement, Deborah number, solvent viscosity ratio, viscosity ratio, and capillary number. We attempted to find the critical capillary number for initiation of drop breakup. Observations from present study will give valuable insights into deformation and breakup patterns of drug carriers inside constricted microcapillaries. The simulations of the two-phase viscoelastic drop─Newtonian matrix system were performed on an open-source solver, Basilisk.

Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis.

[Figure: see text].

Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives.

The synthesis of hitherto unreported 3-sulfenylindole derivatives is achieved from 4-hydroxy-2H-chromene-2-thione (1) and indole (2) by employing an oxidative cross-dehydrogenative coupling reaction using a combination of 10 mol% of molecular iodine and 1 equivalent of TBHP in DMSO at room temperature. Then, the 3-sulfenylindole derivatives 3a, 3b, 3d, 3f, 3 h, and 3 k were converted into their corresponding sulfone derivatives because of lead likeness properties. Subsequently, a target prediction and docking study of six sulfone derivatives (5a-f) was performed, and four sulfones, namely 5a, 5d, 5e, and 5f, were selected for further in-vitro studies. The four sulfones mentioned above exhibited prominent anti-proliferative activity on breast cancer (MCF7) cell lines. In addition, this reaction was exergonic through quantum chemical analysis of the mechanistic steps. The salient features of this reaction are mild reaction conditions, good yields, and broad substrate scope.

Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques.

Governing protein-protein interaction networks are the cynosure of cell signaling and oncogenic networks. Multifarious processes when aligned with one another can result in a dysregulated output which can result in cancer progression. In the current research, one such network of proteins comprising VANG1/SCRIB/NOS1AP, which is responsible for cell migration, is targeted. The proteins are modeled using in-silico approaches, and the interaction is visualized utilizing protein-protein docking. Designing drugs for the convoluted protein network can serve as a challenging task that can be overcome by fragment-based drug designing, a recent game-changer in the computational drug discovery strategy for protein interaction networks. The model is exposed to the extraction of hotspots, also known as the restrained regions for small molecular hits. The hotspot regions are subjected to a library of generated fragments, which are then recombined and rejoined to develop small molecular disruptors of the macromolecular assemblage. Rapid screening methods using pharmacokinetic tools and 2D interaction studies resulted in four molecules that could serve the purpose of a disruptor. The final validation is executed by long-range simulations of 100 ns and exploring the stability of the complex using several parameters leading to the emergence of two novel molecules VNS003 and VNS005 that could be used as the disruptors of the protein assembly VANG1/SCRIB/NOS1AP. Also, the molecules were explored as single protein targets approbated via molecular docking and 100 ns molecular dynamics simulation. This concluded VNS003 as the most suitable inhibitor module capable of acting as a disruptor of a macromolecular assembly as well as acting on individual protein chains, thus leading to the primary hindrance in the formation of the protein interaction complex.

The Hawthorne Effect: Quality and Outcomes in Neurosurgery.

Measure something, and it gets better-this is what is called as the Hawthorne effect (also known as the observer effect). The Hawthorne factory experiments in 1920s were remarkable industrial data collection and analysis exercises that lead to Edwards Deming's quality revolution. The Harvard Medical Practice Study (1991), Leape's "Error in Medicine" (1994), and the Bristol pediatric cardiac report (2001) are among many documents that have revealed the huge gap between best practices and actual medical practice. Alarmed by the poor standards of quality at the most respected institutions, the medical fraternity therefore began visiting facilities in different fields and observing their quality assessment processes. The next leap for neurosurgery is to realize that it is unacceptable to treat patients with no regard for the standard of clinical outcomes. The traditional neurosurgery residency training has long ignored the most important issues of self-assessment, reappraisal, relearning, and measurement of skill and surgical outcomes. However, the experience taken from disparate fields, especially cardiac surgery, may encourage research and progress in measurement and improvement of quality in neurosurgery. Like cardiac surgeons, neurosurgeons must examine and analyze the results of their interventions. The concept of quality measurement is the most important single advance we can make in neurosurgery practice. Meticulous and precise measurement of outcomes will allow future progress of our specialty.

Transport Behavior of Commercial Anticancer Drug Protein-Bound Paclitaxel (Paclicad) in a Micron-Sized Channel.

Protein-bound paclitaxel has been developed clinically as one of the most successful chemotherapy drugs for the treatment of a wide variety of cancers. However, these medications, due to their nanoscale properties, may often induce capillary blocking while migrating through minute blood vessels. Considering the detrimental impact of this restriction, we investigated the transport of protein-bound paclitaxel, Paclicad, in a 7 µm microchannel mimicking the identical mechanical confinement of the blood capillaries. The drug was reported to migrate through a constricted microchannel without obstruction at a solution flow rate of 20-50 µL/h. The onset of an agglomeration site was observed at higher flow rates of 70-90 µL/h, while complete capillary obstruction was observed at 100 µL/h. The mobility of the particles was also calculated, and the results suggested that the presence of varying cross-sections affects the mobility of the drug particles. The trajectory of the particle migration was observed to be less tortuous at the higher flow rate, but the tortuous nature appeared to increase with the presence of agglomeration sites in the flow field. The experimental results were also compared with the computational model of the drug particle. The drug particle was modeled both as Newtonian and as an FENE-P viscoelastic drop. The drop interface tracking was done by the VOF method using the open source software Basilisk. The particle displacement was better estimated by both the FENE-P and Newtonian model at a flow rate of 30 µL/h, while deviation was observed at a flow rate of 50 µL/h. The FENE-P model was observed to show higher deformation than the Newtonian model at both flow rates. The experimental results provided better insight into the agglomeration tendency of Paclicad, migrating through a constricted microchannel at higher flow rates. The numerical model could be further employed to understand the more complex intravenous transport of drugs.

A photo-responsive fluorescent amphiphile for target-specific and image-guided drug delivery applications.

Multifunctional drug delivery systems are the centerpiece of effective chemotherapeutic strategies. Herein, we report the synthesis of an acetazolamide-linked cyanine-3-based NIR-responsive fluorescent macrocyclic amphiphile that self-assembled into spherical nanostructures in the aqueous medium via a J-aggregation pattern. The amphiphile shows various favorable properties of lipids. The photocleavage of the strained dioxacycloundecine ring induces spherical to nanotubular self-assembly with concomitant release of an encapsulated anticancer drug, doxorubicin (Dox), in a controlled manner. The CA-IX targeted amphiphile also showed lower cytotoxicity, effective cellular uptake, and Dox delivery to the model carcinoma cells.

Neuroinflammation in Murine Cirrhosis Is Dependent on the Gut Microbiome and Is Attenuated by Fecal Transplant.

Cirrhosis and hepatic encephalopathy (HE) is associated with an altered gut-liver-brain axis. Fecal microbial transplant (FMT) after antibiotics improves outcomes in HE, but the impact on brain function is unclear. The aim of this study is to determine the effect of colonization using human donors in germ-free (GF) mice on the gut-liver-brain axis. GF and conventional mice were made cirrhotic using carbon tetrachloride and compared with controls in GF and conventional state. Additional GF mice were colonized with stool from controls (Ctrl-Hum) and patients with cirrhosis (Cirr-Hum). Stools from patients with HE cirrhosis after antibiotics were pooled (pre-FMT). Stools from the same patients 15 days after FMT from a healthy donor were also pooled (post-FMT). Sterile supernatants were created from pre-FMT and post-FMT samples. GF mice were colonized using stools/sterile supernatants. For all mice, frontal cortex, liver, and small/large intestines were collected. Cortical inflammation, synaptic plasticity and gamma-aminobutyric acid (GABA) signaling, and liver inflammation and intestinal 16s ribosomal RNA microbiota sequencing were performed. Conventional cirrhotic mice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intestinal dysbiosis compared with other groups. Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lower synaptic plasticity compared with Ctrl-Hum mice. This was associated with greater dysbiosis but no change in liver histology. Pre-FMT material colonization was associated with neuroinflammation and microglial activation and dysbiosis, which was reduced significantly with post-FMT samples. Sterile pre-FMT and post-FMT supernatants did not affect brain parameters. Liver inflammation was unaffected. Conclusion: Fecal microbial colonization from patients with cirrhosis results in higher degrees of neuroinflammation and activation of GABAergic and neuronal activation in mice regardless of cirrhosis compared with those from healthy humans. Reduction in neuroinflammation by using samples from post-FMT patients to colonize GF mice shows a direct effect of fecal microbiota independent of active liver inflammation or injury.

Unfolding transmembrane TNFα dynamics in cancer therapeutics.

Cytokines are a group of glycoprotein signaling mediators, which play essential roles in maintaining several complex physiological functions of our body. TNFα is such a pleiotropic cytokine, which involves maintaining a plethora of immune responses. Initially, TNFα is synthesized as a 26 kDa full-length transmembrane form, which is enzymatically cleaved to produce the soluble circulating 17 kDa TNFα. Although the anti-cancer potential of soluble TNFα was discovered more than a century back, its dual ability to promote tumor, posed a major hindrance in finding its acceptance as a proper anti-cancer molecule. In contrast, the membrane-tethered tmTNFα holds the potential of tumor regression without initiating cell proliferation. The membrane-tethered form of TNFα is the physiological precursor of soluble TNFα that remains biologically active and is capable of initiating signaling cascades after binding with the TNFα receptors- TNFR I and TNFR II. In this review, we emphasize on the basic biology and molecular aspects of tmTNFα for its anti-cancer potential.

Multifunctional liquid marbles to stabilize and transport reactive fluids.

The self-organized transport and delivery of reactive liquids without spillage or loss of activity have been among the most daunting challenges for a long time. In this direction, we employ the concept of forming "liquid marbles" (LMs) to encapsulate and transport reactive hydrogen peroxide (H2O2) coated with functional microparticles. For example, peroxide marbles coated with a toner ink display remote-controlled magnetotactic movement inside a fluidic medium, thus overcoming the weaknesses associated with use of the bare droplets. Interestingly, in such a scenario, the coating of the marbles could also be removed or reformed by bringing the magnet towards or away from the marble. In this way, this process could ensure an on-demand remotely guided coating on the peroxide droplet or its removal. The liquid marbles carrying peroxide solutions are found to preserve the activity of the peroxide and exhibit a low evaporation rate compared with the uncoated peroxide fuel. Interestingly, oil droplets floating on the water could be recovered by introducing the armoured LMs into water under magnetic guidance. Further, the functionalized marbles could be employed as suicide bags for the on-demand delivery of reactive materials in targeted locations. Preliminary research on the antibacterial activity of such liquid marbles has proven to be effective in bacterial killing, which may create new avenues for emerging antibacterial and antibiofilm applications. Finally, such functionalized LMs have been employed to investigate the effects of surface charge on attachment of recombinant Escherichia coli bacteria expressing green fluorescent protein and monitoring the real-time imaging of bacterial death attached to the marble surface.

Copper(I)-Mediated Cascade Annulation via Dual C-H/C-H Activation: Access to Benzo[a]carbazolic AEEgens.

A Cu(I)-mediated cascade cyclization/annulation of unprotected o-alkynylanilines with maleimides in one pot is developed. The protocol offers sequential formation of one C-N and two C-C bonds to deliver fused benzo[a]carbazoles having free NH skeletons. The annulated products display fluorescence emission in the range of 485-502 nm with a large Stokes shift and fluorescence lifetime of ∼17 ns. The annulated 3aa displays AEE behavior in the ethanol/hexane system and possesses marigold-flower-like morphology at the aggregated state. Cell viability assays enumerate biocompatible AEEgens, while their high intracellular fluorescence depicts cell imaging applicability.

Synthesis of biologically active fused 1,4-oxathiin derivatives from 4-hydroxydithiocoumarins, arylacetylenes and dimethyl sulfoxide by Cu(i)-catalyzed C-H functionalization and cross-dehydrogenative C-S coupling reactions.

The hitherto unreported 2-aryl-10H-thiochromeno[3,2-b][1,4]oxathiin-10-one derivatives are obtained in a single pot from 4-hydroxydithiocoumarins, arylacetylenes and dimethyl sulfoxide in the presence of 10 mol% CuI and K2CO3 in an oil bath at 70 °C. The novelties of the present protocol are (i) selective C-H functionalization at the C-3 position of 4-hydroxydithiocoumarin, (ii) regioselective hydrothiolation with arylacetylenes and (iii) concomitant cyclisation. The major advantages are mild reaction conditions, broad substrate scope and good yield. Among the synthesized compounds, the following five compounds 3aa, 3bd, 3ec, 3fa, and 3fd showed anticancer activity against a human breast cancer cell line (MCF-7) and a cervical cancer cell line (HeLa).

Real-time transport kinetics of drug encapsulated nanoparticles into apoptotic cancer cells inside microchannels.

Development of nanocomposites as drug delivery vectors is a burgeoning field of research. However, the usage of such newly invented nanomatrices are often limited by the shortcomings associated with the testing of their real-life efficacy. Many drugs fail because a monolayer framework ofin vitrocell line screening method does not adequately mimic thein vivothree-dimensional microenvironments. In this direction, the study unveils the development of a continuous flow microreactor wherein the cellulose acetate nanoparticles (CANPs) with varying sizes are prepared before encapsulating them with an anticancer drug-doxorubicin (DOX). Subsequently, anin vitromicrofluidic drug delivery model has been introduced in which the HeLa cells specific to cervical cancer is treated with the DOX encapsulated CANPs-DOX@CANPs. Thereafter, the transport of the drugs from the fluidic to cellular environment, their transport inside the cell, and the real-time kinetics of the cancer cell apoptosis have been analyzed systematically to uncover the real-time efficacy and cytotoxic effects of the nanocomposite. Interestingly, experiments reveal, (i) ∼89.4% DOX loading on the nanocomposite owing to a facile electrostatic interaction, (ii) a pH-dependent controlled release of drug during the transport with the cancer cells, and (iii) cell apoptosis after the diffused inoculation of the drug. A mathematical model has been developed to emulate the drug transport from the surrounding fluid to the cancer cells. Experiments together with the mathematical model uncover that the kinetics of cancer cell death is limited by the reaction at the cell-nucleus. The microfluidic model has shown significant potential to be translated as a useful tool for the real-time and on-demandin vitroscreening of the cancer drugs.

Dietary Supplementation with Galactooligosaccharides Attenuates High-Fat, High-Cholesterol Diet-Induced Glucose Intolerance and Disruption of Colonic Mucin Layer in C57BL/6 Mice and Reduces Atherosclerosis in Ldlr-/- Mice.

BACKGROUND: A Western-type diet (WD), rich in fat and cholesterol but deficient in fiber, induces development of diabetes and atherosclerosis. Colonic bacteria use the gut's mucous lining as an alternate energy source during periods of fiber deficiency, resulting in intestinal barrier erosion. OBJECTIVE: We hypothesized that supplementing a WD with galactooligosaccharide (GOS) fiber would attenuate WD-induced mucin layer disruption and attenuate development of metabolic diseases. METHODS: C57BL/6 mice (both sexes, 8-10 wk of age) were fed a standard rodent diet (TD7012, reference) or a high-fat, high-cholesterol-containing WD (TD88137, 21% fat, 0.15% cholesterol, 19.5% caesin) or a WD supplemented with 5% GOS fiber (TD170432, WD + GOS) for 16 wk. WD-fed mice that were gavaged daily with curcumin (100 mg/kg) served as positive controls. Glucose tolerance, colonic mucin layer, gene expression, and circulating macrophage/neutrophil levels were determined. Hyperlipidemic Ldlr-/- mice (both sexes, 8-10 wk of age) fed a WD with or without GOS supplementation (for 16 wk) were used to assess plasma LPS and atherosclerosis. Effects of dietary supplementation on different parameters were compared for each genotype. RESULTS: Compared with a WD, glucose tolerance was significantly improved in male C57BL/6 mice fed a WD + GOS (mean ± SEM: AUC = 53.6 ± 43.9 compared with 45.4 ± 33.3 g ⋅ min/dL; P = 0.015). Continuity of colonic mucin layer (MUC-2 expression) was improved in mice receiving GOS supplementation, indicating improved intestinal barrier. GOS supplementation also reduced circulating macrophages (30% decrease) and neutrophils (60% decrease), suggesting diminished systemic inflammation. In Ldlr-/- mice, GOS supplementation significantly reduced plasma LPS concentrations (mean ± SEM: 0.81 ±  0.43 EU/mL compared with 0.32 ± 0.26 EU/mL, P   < 0.0001, in females and 0.56 ± 0.24 EU/mL compared with 0.34 ± 0.12 EU/mL, P = 0.036, in males), improved glucose tolerance in male mice, and attenuated atherosclerotic lesion area (mean ± SEM: 54.2% ± 6.19% compared with 43.0% ± 35.12%, P   = 0.0006, in females and 54.6% ± 3.99% compared with 43.1% ± 8.11%, P = 0.003, in males). CONCLUSIONS: GOS fiber supplementation improves intestinal barrier in C57BL/6 and Ldlr-/- mice and significantly attenuates WD-induced metabolic diseases and, therefore, may represent a novel strategy for management of these diseases.

Newly synthesized 3-sulfenylindole derivatives from 4-hydroxydithiocoumarin using an oxidative cross dehydrogenative coupling reaction (OCDCR): potential lead molecules for antiproliferative activity.

An expedient and efficient synthetic method was developed for the oxidative cross dehydrogenative coupling reaction between 4-hydroxydithiocoumarin and indole at the C-3 position regio-selectively using a combination of 10 mol% molecular iodine and TBHP in the presence of 10 mol% CuBr2 as an additive at room temperature. Mild reaction conditions, good yields and a broad substrate scope are some of the salient features of the present protocol. Additionally, the synthesized 3-sulfenylindoles derived from 4-hydroxydithiocoumarin were converted into biologically active sulfone derivatives. Interestingly, some of the compounds exhibit anti-cell proliferative activity on breast cancer (MCF-7) cells due to reactive oxygen species (ROS) mediated cell damage.