Current pharmacophore based approaches for the development of new anti-Alzheimer's agents.

Amyloid beta peptide (Aβ) and hyperphosphorylated neuronal tau proteins accumulate in neurofibrillary tangles in Alzheimer's disease (AD), a chronic neurodegenerative illness. Chronic inflammation in the brain, which promotes disease progression, is another feature of the Alzheimer's disease pathogenesis. Approximately 60-70 % of dementia cases are caused by AD.

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.

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.

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.

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

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.

Synthesis of triazole bridged -glycosides of pyrazolo[1,5-]pyrimidinones as anticancer agents and their 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 -glycosides of pyrazolo[1,5-]pyrimidinones, employing a microwave-assisted synthetic approach '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 -glycosides of pyrazolo[1,5-]pyrimidinones.

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.

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.

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.

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.

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

An efficient and unique approach to synthesize isatin (indole-2,3-dione) from 2-aminoacetophenone under electrochemical conditions supported by I-DMSO through C-N cross-coupling and C(sp)-H/C(sp)-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.

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.

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 and 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 .

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

A metal free synthesis of enantiopure 2,3-dideoxy-α, β-unsaturated carbohydrate enals (Perlin aldehydes), in CHCN-0.02 N HSO in water (1:1, v/v) with 0.5 equivalent additives (4-hydroxy-6-methyl-2-pyrone or 4-amino coumarin), has been reported.

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 in the low redox potential range of -0.14 to 0.

Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors.

The influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses.

Metalloprotease Gp63-Targeting Novel Glycoside Exhibits Potential Antileishmanial Activity.

Visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) affect most of the poor populations worldwide. The current treatment modalities include liposomal formulation or deoxycholate salt of amphotericin B, which has been associated with various complications and severe side effects. Encouraged from the recent marked antimalarial effects from plant-derived glycosides, in this study, we have exploited a green chemistry-based approach to chemically synthesize a library of diverse glycoside derivatives (Gly1-12) and evaluated their inhibitory efficacy against the AG83 strain of .

Biomarkers and Precision Medicine in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, which is the fifth major cause of mortality for people over 65 years. While some of the hereditary genetic risk factors can be connected to the known amyloid and tau hypothesis, many treatments targeting this pathophysiology have failed in clinical trials or ineffectiveness of the drugs are attributed to the heterogeneous and multifactorial nature of AD. Thus, there is an urgent need to focus on finding therapeutic targets that can mitigate disease progression on patient based personalized medicine.

Precision medicine in public health in India: Nascent but poised in the right direction.

Precision medicine (PM) in public health offers a new paradigm. Over a past few decades, there has been very rapid development in science and technology, especially in medical-clinical research to enhance the likelihood of preventive treatment which is personalized to an individual. This combined with digital health and accessibility of environmental and behavioral data offers a unique opportunity for specific prevention advice to individuals and thus to population at large.