Synthesis and biological evaluation of Halogen-Substituted novel α-Ketoamides as potential protein aggregation modulators in Alzheimer's disease.

The escalating prevalence of Alzheimer's disease (AD) has prompted extensive research into potential therapeutic interventions, with a specific focus on molecular targets such as amyloid beta (Aß) and tau protein aggregation. In this study, a series of α-ketoamide derivatives was synthesized from ß,γ-unsaturated α-keto thioesters, achieving high purity and good yield. Thioflavin T based Aß aggregation assay identified four promising compounds (BD19, BD23, BD24, and BD27) that demonstrated significant inhibitory effects on Aß aggregation. BD23, selected for its better solubility (0.045 ± 0.0012 mg/ml), was further subjected to in vitro Parallel Artificial Membrane Permeability Assay to determine the Blood-Brain-Barrier permeability and emerged as BBB permeable with permeability rate (Pe) of 10.66 ± 8.11 × 10-6 cm/s. In addition to its Aß inhibitory properties, BD23 exhibited significant inhibition of heparin-induced tau aggregation and demonstrated non-toxicity in SHSY5Y cell lines. Subsequent in vivo assays were conducted, administering compound BD23 to an Aß induced mouse model of AD at various doses (1, 2, & 5 mg/kg). The results revealed a noteworthy enhancement in cognitive functions, particularly when BD23 was administered at a dosage of 5 mg/kg, comparable to the effects observed with the standard dose of Donepezil (DNP). In silico investigations, including molecular docking, molecular dynamics simulations, and Density Functional Theory calculations provided insights into BD23's interactions with the targets and electronic properties. These analyses contribute to the understanding of the therapeutic potential of the lead compounds BD23 which further pave the way for further exploration of its therapeutic potential in the context of AD.

Caspase-driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications.

Apoptosis is the cell's natural intrinsic regulatory mechanism of normal cells for programmed cell death, which plays an important role in cancer as a classical mechanism of tumor cell death causing minimal inflammation without causing damage to other cells in the vicinity. Induction of apoptosis by activation of caspases is one of the primary targets for cancer treatment. Over the years, a diverse range of natural, synthetic, and semisynthetic compounds and their derivatives have been investigated for their caspase-mediated apoptosis-induced anticancer activities. The review aims to compile the preclinical evidence and highlight the critical mechanistic pathways related to caspase-induced cell apoptosis in cancer treatment. The focus is placed on the key components of the mechanisms, including their chemical nature, and specific attention is given to phytochemicals derived from natural sources and synthetic and semisynthetic compounds. 180+ compounds from the past two decades with potential as anticancer agents are discussed in this review article. By summarizing the current knowledge and advancements in this field, this review provides a comprehensive overview of potential therapeutic strategies targeting apoptosis in cancer cells. The findings presented herein contribute to the ongoing efforts to combat cancer and stimulate further research into the development of effective and targeted anticancer therapies.

Combination chemotherapy in rodents: a model for chemotherapy-induced neuropathic pain and pharmacological screening.

Chemotherapy-induced neuropathic pain (CINP) remains a therapeutic challenge, with no US-FDA approved drugs or effective treatments available. Despite significant progress in unravelling the pathophysiology of CINP, the clinical translation of this knowledge into tangible outcome remains elusive. Here, we employed behavioural and pharmacological approaches to establish and validate a novel combination-based chemotherapeutic model of peripheral neuropathy. Male Sprague Dawley rats were subjected to chemotherapy administration followed by assessment of pain behaviour at different time-points post-chemotherapy. Paclitaxel-treated animals displayed an enhanced thermal and mechanical hypersensitivity from day four onwards which continued till day thirty-five post last paclitaxel injection. Notably, rats subjected to combination chemotherapy, displayed prolonged hypersensitivity that emerged on day four and persisted until day fifty-six. RT-PCR analysis revealed significant upregulation in DRG and spinal mRNA expressions of TRP channels (TRPA1, TRPV1, & TRPM8), pro-inflammatory cytokines (TNF-α & IL-1ß) and neuropeptides, Substance P and CGRP in both the pain models. Interestingly, the combination chemotherapy model demonstrated a significant increase in DRG and spinal NR2B expressions compared to rats solely treated with paclitaxel. Pharmacological investigations revealed that gabapentin treatment substantially mitigates pain hypersensitivity in both the combined chemotherapy and paclitaxel-administered groups, with the simultaneous reversal of cellular and molecular changes observed in the lumbar DRG and spinal cord of rats. The findings from this study suggests that combination chemotherapy model exhibits heightened and prolonged hypersensitivity in comparison to the conventional paclitaxel-induced neuropathic pain model. This model not only recapitulates clinical biomarkers of neuropathy but also presents a potential alternative platform for screening analgesic drugs targeted at CINP.

Organocatalyzed Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazolyl Glycoconjugates.

A novel organocatalyzed [3+2] cycloaddition reaction of nitroolefins with glycosyl azides as well as organic azides has been developed for successful construction of 1,5-disubstituted triazolyl glycoconjugates. This metal-free and acid-free, regioselective synthetic protocol proceeds in the presence of only Schreiner thiourea organocatalysts, which enable the required activation of nitroolefins through double hydrogen bonding. The straightforward, operationally simple, and regioselectivity of this methodology, complementing to the classical RuAAC catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles. In the presence of catalytic amount of Schreiner thiourea organocatalyst, organic azides react with a broad array of nitroolefins producing a series of diverse 1,5-disubstituted 1,2,3- triazoles in good yields with excellent regioselectivity.

Growing Impact of Intramolecular Click Chemistry in Organic Synthesis.

Click Chemistry, a modular, rapid, and one of the most reliable tool for the regioselective 1,2,3-triazole forming [3+2] reaction of organic azide and terimal alkyne is widely explored in various emerging domains of research ranging from chemical biology to catalysis and medicinal chemistry to material science. This regioselective reaction from a diverse range of azido-alkyne scaffolds has been well performed in both intermolecular as well as intramolecular fashions. In comparison to the intermolecular metal (Cu/Ru/Ni) variant of 'Click Chemistry', the intramolecular click tool is little addressed. The intramolecular click chemistry is exemplified as a mordern tool of cyclization which involves metal-catalyzed (CuAAC/RuAAC) cyclization, organo-catalyzed cyclization, and thermal-induced topochemical reaction. Thus, we report herein the recent approaches on intramolecular azide-alkyne cycloaddition 'Click Chemistry' with their wide-spread emerging applications in the developement of a diverse range of molecules including fused-heterocycles, well-defined peptidomemics, and macrocyclic architectures of various notable features.

Triazole-Appended Glycohybrid/CuI-Catalyzed C-C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars.

This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60-70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope.

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications.

Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.

LEO1 is a partner for Cockayne syndrome protein B (CSB) in response to transcription-blocking DNA damage.

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as an interacting protein partner of full-length and C-terminal (Pro1010-Cys1493) CSB in two independent screens. LEO1 is a member of the RNA polymerase associated factor 1 complex (PAF1C) with roles in transcription elongation and chromatin modification. Supportive of the Y2H results, purified, recombinant LEO1 and CSB directly interact in vitro, and the two proteins exist in a common complex within human cells. In addition, fluorescently tagged LEO1 and CSB are both recruited to localized DNA damage sites in human cells. Cell fractionation experiments revealed a transcription-dependent, coordinated association of LEO1 and CSB to chromatin following either UVC irradiation or cisplatin treatment of HEK293T cells, whereas the response to menadione was distinct, suggesting that this collaboration occurs mainly in the context of bulky transcription-blocking lesions. Consistent with a coordinated interaction in DNA repair, LEO1 knockdown or knockout resulted in reduced CSB recruitment to chromatin, increased sensitivity to UVC light and cisplatin damage, and reduced RNA synthesis recovery and slower excision of cyclobutane pyrimidine dimers following UVC irradiation; the absence of CSB resulted in diminished LEO1 recruitment. Our data indicate a reciprocal communication between CSB and LEO1 in the context of transcription-associated DNA repair and RNA transcription recovery.

Current and emerging roles of Cockayne syndrome group B (CSB) protein.

Cockayne syndrome (CS) is a segmental premature aging syndrome caused primarily by defects in the CSA or CSB genes. In addition to premature aging, CS patients typically exhibit microcephaly, progressive mental and sensorial retardation and cutaneous photosensitivity. Defects in the CSB gene were initially thought to primarily impair transcription-coupled nucleotide excision repair (TC-NER), predicting a relatively consistent phenotype among CS patients. In contrast, the phenotypes of CS patients are pleiotropic and variable. The latter is consistent with recent work that implicates CSB in multiple cellular systems and pathways, including DNA base excision repair, interstrand cross-link repair, transcription, chromatin remodeling, RNAPII processing, nucleolin regulation, rDNA transcription, redox homeostasis, and mitochondrial function. The discovery of additional functions for CSB could potentially explain the many clinical phenotypes of CSB patients. This review focuses on the diverse roles played by CSB in cellular pathways that enhance genome stability, providing insight into the molecular features of this complex premature aging disease.

Design, Synthesis, and Docking Study of Quinine-9-Triazolyl Conjugates.

To develop a better chemotherapeutically potential candidate for lung cancer treatment and cure with repurposed motifs, quinine has been linked with biocompatible CuAAC-inspired regioselective 1,2,3-triazole linker and a series of ten novel 1,2,3-triazolyl-9-quinine conjugates have been developed by utilizing click conjugation of glycosyl ether alkynes with 9-epi-9-azido-9-deoxy-quinine under standard click conditions. In parallel, the docking study indicated that the resulting conjugates have an overall appreciable interaction with ALK-5 macromolecules. Moreover, the mannose-triazolyl conjugate exhibited the highest binding interactions of -7.6 kcal/mol with H-bond interaction with the targeted macromolecular system and indicate the hope for future trials for anti-lung cancer candidates.

Development and Evaluation of Amorphous Solid Dispersion of Riluzole with PBPK Model to Simulate the Pharmacokinetic Profile.

In the current work, screening of polymers viz. polyacrylic acid (PAA), polyvinyl pyrrolidone vinyl acetate (PVP VA), and hydroxypropyl methyl cellulose acetate succinate (HPMC AS) based on drug-polymer interaction and wetting property was done for the production of a stable amorphous solid dispersion (ASD) of a poorly water-soluble drug Riluzole (RLZ). PAA showed maximum interaction and wetting property hence, was selected for further studies. Solid state characterization studies confirmed the formation of ASD with PAA. Saturation solubility, dissolution profile, and in vivo pharmacokinetic data of the ASD formulation were generated in rats against its marketed tablet Rilutor. The RLZ:PAA ASD showed exponential enhancement in the dissolution of RLZ. Predicted and observed pharmacokinetic data in rats showed enhanced area under curve (AUC) and Cmax in plasma and brain with respect to Rilutor. Furthermore, a physiologically based pharmacokinetic (PBPK) model of rats for Rilutor and RLZ ASD was developed and then extrapolated to humans where physiological parameters were changed along with a biochemical parameter. The partition coefficient was kept similar in both species. The model was used to predict different exposure scenarios, and the simulated data was compared with observed data points. The PBPK model simulated Cmax and AUC was within two times the experimental data for plasma and brain. The Cmax and AUC in the brain increased with ASD compared to Rilutor for humans showing its potential in improving its biopharmaceutical performance and hence enhanced therapeutic efficacy. The model can predict the RLZ concentration in multiple compartments including plasma and liver.

DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging.

Genetic information is constantly being attacked by intrinsic and extrinsic damaging agents, such as reactive oxygen species, atmospheric radiation, environmental chemicals, and chemotherapeutics. If DNA modifications persist, they can adversely affect the polymerization of DNA or RNA, leading to replication fork collapse or transcription arrest, or can serve as mutagenic templates during nucleic acid synthesis reactions. To combat the deleterious consequences of DNA damage, organisms have developed complex repair networks that remove chemical modifications or aberrant base arrangements and restore the genome to its original state. Not surprisingly, inherited or sporadic defects in DNA repair mechanisms can give rise to cellular outcomes that underlie disease and aging, such as transformation, apoptosis, and senescence. In the review here, we discuss several genetic disorders linked to DNA repair defects, attempting to draw correlations between the nature of the accumulating DNA damage and the pathological endpoints, namely cancer, neurological disease, and premature aging.

Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones.

The glycosyl 1,2,3-triazoles are expediently accessible from readily available sugar-derived glycosyl azide by utilizing modular CuAAC "Click Chemistry", and the resulting glycohybrid skeleton possesses efficient metal-coordinating centers that support a wide range of metal-mediated efficient catalysis in various imperative organic transformations. Here, we designed and developed pyridyl glycosyl triazoles by employing the CuAAC reaction of d-glucose-derived glycosyl azides and alkynyl pyridines. These pyridyl glycosyl triazoles with Cu(I) salt were explored as an efficient catalyst to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by the domino/tandem cross-coupling reaction of various N-substituted o-halobenzamides with cyanamide and formamide, respectively. The devised protocol has some notable features, including biocompatibility, low cost, easily accessible starting materials for the glycosyl ligands, high yield, broad spectrum, low catalytic loading, and mild reaction conditions.

Synthesis and evaluation of dual fatty acid amide hydrolase-monoacylglycerol lipase inhibition and antinociceptive activities of 4-methylsulfonylaniline-derived semicarbazones.

Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are promising targets for neuropathic pain and other CNS disorders. Based on our previous lead compound SIH 3, we designed and synthesized a series of 4-methylsulfonylphenyl semicarbazones and evaluated for FAAH and MAGL inhibition properties. Most of the compounds showed potency towards both enzymes with leading FAAH selectivity. Compound (Z)-2-(2,6-dichlorobenzylidene)-N-(4-(methylsulfonyl)phenyl)hydrazine-1-carboxamide emerged as the lead inhibitor against both FAAH (IC50 = 11 nM) and MAGL (IC50 = 36 nM). The lead inhibitor inhibited FAAH by non-competitive mode, but showed a mixed-type inhibition against MAGL. Molecular docking study unveiled that the docked ligands bind favorably to the active sites of FAAH and MAGL. The lead inhibitor interacted with FAAH and MAGL via π-π stacking via phenyl ring and hydrogen bonding through sulfonyl oxygen atoms or amide NH. Moreover, the stability of docked complexes was rationalized by molecular simulation studies. PAMPA assay revealed that the lead compound is suitable for blood-brain penetration. The lead compound showed better cell viability in lipopolysaccharide-induced neurotoxicity assay in SH-SY5Y cell lines. Further, in-vivo experiments unveiled that dual inhibitor was safe up to 2000 mg/kg with no hepatotoxicity. The dual FAAH-MAGL inhibitor produced significant anti-nociceptive effect in the CCI model of neuropathic pain without altering locomotion activity. Lastly, the lead compound exhibited promising ex-vivo FAAH/MAGL inhibition activity at the dose of 10 mg/kg and 20 mg/kg. Thus, these findings suggest that the semicarbazone-based lead compound can be a potential template for the development of agents for neuropathic pain.

Multifactorial pathways in burn injury-induced chronic pain: novel targets and their pharmacological modulation.

Burn injuries are among the highly prevalent medical conditions worldwide that occur mainly in children, military veterans and victims of fire accidents. It is one of the leading causes of temporary as well as permanent disabilities in patients. Burn injuries are accompanied by pain that persists even after recovery from tissue damage which puts immense pressure on the healthcare system. The pathophysiology of burn pain is poorly understood due to its complex nature and lack of considerable preclinical and clinical shreds of evidence, that creates a substantial barrier to the development of new analgesics. Burns damage the skin layers supplied with nociceptors such as NAV1.7, TRPV1, and TRPA1. Burn injury-mediated co-localization and simultaneous activation of TRPA1 and TRPV1 in nociceptive primary afferent C-fibers which contributes to the development and maintenance of chronic pain. Burn injuries are accompanied by central sensitization, a key feature of pain pathophysiology mainly driven by a series of cascades involving aberrations in the glutamatergic system, microglial activation, release of neuropeptides, cytokines, and chemokines. Activation of p38 mitogen-activated protein kinase, altered endogenous opioid signaling, and distorted genomic expression are other pathophysiological factors responsible for the development and maintenance of burn pain. Here we discuss comprehensive literature on molecular mechanisms of burn pain and potential targets that could be translated into near future therapeutics.

Decrypting the cellular and molecular intricacies associated with COVID-19-induced chronic pain.

Pain is one of the clinical manifestations that can vary from mild to severe symptoms in COVID-19 patients. Pain symptoms can be initiated by direct viral damage to the tissue or by indirect tissue injury followed by nociceptor sensitization. The most common types of pain that are reported to occur in COVID-19 patients are headache, myalgia, and chest pain. With more and more cases coming in the hospitals, many new and unique symptoms of pain are being reported. Testicular and abdominal pain are rare cases of pain that are also being reported and are associated with COVID-19. The SARS-CoV-2 virus has a high affinity for angiotensin-converting enzyme-2 receptor (ACE-2) which acts as an entry point for the virus. ACE-2/ Ang II/AT 1 receptor also participates directly in the transmission of pain signals from the dorsal horn of the spinal cord. It induces a series of complicated responses in the human body. Among which the cytokinetic storm and hypercoagulation are the most prominent pathways that mediate the sensitization of sensory neurons facilitating pain. The elevated immune response is also responsible for the activation of inflammatory lipid mediators such as COX-1 and COX-2 enzymes for the synthesis of prostaglandins (PGs). PG molecules especially PGE2 and PGD2 are involved in the pain transmission and are found to be elevated in COVID-19 patients. Though arachidonic acid pathway is one of the lesser discussed topics in COVID-19 pathophysiology, still it can be useful for explaining the unique and rarer symptoms of pain seen in COVID-19 patients. Understanding different pain pathways is very crucial for the management of pain and can help healthcare systems to end the current pandemic situation. We herein review the role of various molecules involved in the pain pathology of COVID-19.

Immune-microbiome interplay and its implications in neurodegenerative disorders.

The neurodegeneration and its related CNS pathologies need an urgent toolbox to minimize the global mental health burden. The neuroimmune system critically regulates the brain maturation and survival of neurons across the nervous system. The chronic manipulated immunological drive can accelerate the neuronal pathology hence promoting the burden of neurodegenerative disorders. The gut is home for trillions of microorganisms having a mutual relationship with the host system. The gut-brain axis is a unique biochemical pathway through which the gut residing microbes connects with the brain cells and regulates various physiological and pathological cascades. The gut microbiota and CNS communicate using a common language that synchronizes the tuning of immune cells. The intestinal gut microbial community has a profound role in the maturation of the immune system as well as the development of the nervous system. We have critically summarised the clinical and preclinical reports from the past a decade emphasising that the significant changes in gut microbiota can enhance the host susceptibility towards neurodegenerative disorders. In this review, we have discussed how the gut microbiota-mediated immune response inclines the host physiology towards neurodegeneration and indicated the gut microbiota as a potential future candidate for the management of neurodegenerative disorders.

Recent advancements in biomarker research in schizophrenia: mapping the road from bench to bedside.

Schizophrenia (SZ) is a severe progressive neurodegenerative as well as disruptive behavior disorder affecting innumerable people throughout the world. The discovery of potential biomarkers in the clinical scenario would lead to the development of effective methods of diagnosis and would provide an understanding of the prognosis of the disease. Moreover, breakthrough inventions for the treatment and prevention of this mysterious disease could evolve as a result of a thorough understanding of the clinical biomarkers. In this review, we have discussed about specific biomarkers of SZ an emphasis has been laid to delineate (1) diagnostic biomarkers like neuroimmune biomarkers, metabolic biomarkers, oligodendrocyte biomarkers and biomarkers of negative and cognitive symptoms, (2) therapeutic biomarkers like various neurotransmitter systems and (3) prognostic biomarkers. All the biomarkers were evaluated in drug-naïve (at least for 4 weeks) patients in order to achieve a clear comparison between schizophrenic patients and healthy controls. Also, an attempt has been made to elucidate the potential genes which serve as predictors and tools for the determination of biomarkers and would ultimately help in the prevention and treatment of this deadly illness.

Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats.

Chronic pain is among the most burdensome and devastating disorders affecting millions of people worldwide. Recent studies suggest the role of kinesin nanomotors in development and maintenance of chronic pain. KIF17 is a member of kinesin superfamily that binds to NR2B cargo system via mLin10 scaffolding protein and makes the NMDARs functional at cell surface. NMDA receptor activation is known to induce the central sensitization and excitotoxicity which can be recognized by the glial cells followed by the release of cytokine storm at spinal and supraspinal level leading to chronic pain. In this study, we have investigated the role of aurora kinase in the regulation of KIF17 and NR2B trafficking in the animal model of chronic inflammatory pain. Tozasertib (10, 20, and 40 mg/kg i.p.), a pan aurora kinase inhibitor, significantly attenuates acute inflammatory pain and suppresses enhanced pain hypersensitivity to heat, cold, and mechanical stimuli in CFA-injected rats. Molecular investigations suggest enhanced expression of KIF17/mLin10/NR2B in L4-L5 dorsal root ganglion (DRG) and spinal cord of CFA-injected rats which was significantly attenuated on treatment with tozasertib. Moreover, tozasertib treatment significantly attenuated CFA-induced oxido-nitrosative stress and macrophage activation in DRG and microglia activation in spinal cord of rats. Findings from the current study suggest that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling.

Development of Diverse Range of Biologically Relevant Carbohydrate-Containing Molecules: Twenty Years of Our Journey*.

There is an increasing demand for significant amount of carbohydrate-containing molecules owing to their complete chemical, biological, and pharmacological investigations to better understand their role in many important biological events. Clinical studies of a wide range of simple carbohydrates or their derivatives, glycohybrids, glycoconjugates, and neoglycoconjugates have been conducted worldwide for the successful treatment of various frontline diseases. Herein, a brief perspective of carbohydrate-based molecular scaffolding and my experience during the last 20 years in the area of synthetic carbohydrate chemistry, mainly for their impact in drug discovery & development, is presented.