Sushil Kumar Singh

• Managing Director at ICAR ATARI Jodhpur

The cholinergic deficits and deposition of β-amyloid (Aβ) species are regarded as the key events contributing to the progression of Alzheimer’s disease (AD). Herein, a series of novel donor–acceptor architecture-type potential theranostic agents were designed, synthesized, and evaluated for their potential against cholinesterase (ChE) enzymes and d...

Cyclooxygenase‐2 (COX‐2) is an enzyme that plays a crucial role in inflammation by converting arachidonic acid into prostaglandins. The overexpression of enzyme is associated with conditions such as cancer, arthritis, and Alzheimer's disease (AD), where it contributes to neuroinflammation. In silico virtual screening is pivotal in early‐stage drug...

Background/Objectives: Alzheimer’s disease (AD), a complex neurogenerative disorder, manifests as dementia and concomitant neuropsychiatric symptoms, including apathy, depression, and circadian disruption. The pathology involves a profound degeneration of the hippocampus and cerebral cortex, leading to the impairment of both short-term and long-ter...

Cathepsin B is a cysteine protease lysosomal enzyme involved in several physiological functions. Overexpression of the enzyme enhances its proteolytic activity and causes the breakdown of amyloid precursor protein (APP) into neurotoxic amyloid β (Aβ), a characteristic hallmark of Alzheimer’s disease (AD). Therefore, inhibition of the enzyme is a cr...

Ethnopharmacological relevance: Centella asiatica (L.) Urban, is a medicinal herb with rich history of traditional use in Indian subcontinent. This herb has been valued for its diverse range of medicinal properties including memory booster, and also as a folk treatment for skin diseases, wound healing and mild diuretic. Aim of study: Aging is a gra...

Blood‐Brain‐Barrier (BBB) permeability is one of the critical factors in the success and failure of CNS drug development. The most accurate method of measuring BBB permeability involves clinical experiments, which are labour‐intensive and time‐consuming. Thus, numerous efforts were made to use artificial intelligence (AI) to predict molecules′ BBB...

The deposition of β-amyloid (Aβ) plaques in the parenchymal and cortical regions of the brain of Alzheimer's disease (AD) patients is considered the foremost pathological hallmark of the disease. The early diagnosis of AD is paramount in order to effective management and treatment of the disease. Developing near-infrared fluorescence (NIRF) probes...

Dimethyl fumarate (DMF) is the first FDA-approved drug for treating relapsing-remitting multiple sclerosis; but it is susceptible to sublimation leading to its loss during processing. Cocrystals can protect against thermal energy via the interaction of DMF with a coformer via weak forces of interaction. With this hypothesis, we have, for the first...

The β-site APP cleaving enzyme-1 (BACE-1) is one of the key targets for novel drugs to treat Alzheimer’s disease (AD). The BACE-1 plays a key role in the amyloidogenic process, leading to the production of amyloid-β (Aβ) plaques in the brain. In the present work, we have developed an ML model based on the sulfonamides dataset. The best ML model was...

Crystallization has revolutionized the field of solid-state formulations by modulating the physiochemical and release profile of active pharmaceutical ingredients (APIs). Dimethyl fumarate (DF), an FDA-approved first-line drug for relapsing-remitting multiple sclerosis, has a sublimation problem, leading to loss of the drug during its processing. T...

The naturally inspired multitarget-directed ligands (PC01-PC10 and PD01-PD26) were synthesized from piperine for the management of Alzheimer's disease (AD). The compound PD07 showed significant inhibitory activity on ChEs, BACE1, and Aβ1-42 aggregation in in vitro studies. Further, compound PD07 effectively displaced the propidium iodide at the ACh...

Alzheimer's disease (AD) is a progressive brain disorder associated with slow loss of brain functions leading to memory failure and modest changes in behavior. The multifactorial neuropathological condition is due to a depletion of cholinergic neurons and accumulation of amyloid-beta (Aβ) plaques. Recently, a multi-target-directed ligand (MTDL) str...

Histone deacetylase 2 (HDAC2) is associated with various neuropathic degenerative diseases and is considered a novel target for Alzheimer's disease (AD). Elevated levels of HDAC2 trigger excitatory neurotransmission and reduce synaptic plasticity, synaptic number, and memory formation. In the current study, we identified HDAC2 inhibitors using an i...

Vasicine is a pyrroloquinazoline alkaloid, which has been isolated from the plant Adhatoda vasica. Naturally inspired semi-synthetic transformations were prepared using vasicine as a synthetic precursor to overcome Alzheimer's disease (AD). These semi-synthetic analogs exhibited stable interactions and were well resided at AChE and BChE active site...

Background: Alzheimer's disease (AD) is a neurodegenerative disease with cognitive and memory decline. Due to the lack of effective treatment for AD, there is an interest in finding novel compounds to treat AD. The leaves of Adhatoda vasica Nees (AV) exhibited anti-AD effects and known to be rich in pyrroloquinazoline alkaloids. However, the role o...

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca²⁺/CaM)-dependent serine/threonine kinase that is abundantly expressed in the memory- and cognition-related brain areas. DAPK1 is associated with several pathological hallmarks of Alzheimer’s disease (AD); it is an attractive target for designing a novel DAPK1 inhibitor as an effe...

Glucocerebrosidase (GCase), a GBA1 gene-encoded lysosomal enzyme, is a risk factor for Parkinson's disease (PD). Chaperones that increase GCase activity can potentially be disease-modifying agents in PD. To date, none of the registered treatments has demonstrated disease-modifying effects. Thus, chaperones for GCase were identified using in-silico...

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that leads to progressive mental, behavioral, and functional decline including learning ability. The extracellular deposition of amyloid-β (Aβ) peptide as diffused and neuritic plaques and hyper-phosphorylation of tau (p-tau) protein accumulated intracellularly as neurofibrilla...

LIM kinases (LIMKs) are a family of protein kinases involved in the regulation of actin dynamics. There are two isoforms of LIMKs i.e., LIMK1 and LIMK2. LIMK1 is expressed abundantly in neuronal tissues. LIMK1 plays an essential role in the degradation of dendritic spines, which are important for our higher brain functions, such as memory and learn...

Indole-containing small molecules have been reported to have diverse various pharmacological activities. The aromatic heterocyclic scaffold, which resembles various protein structures, has received attention from organic and medicinal chemists. Exploration of indole derivatives in drug discovery has rapidly yielded a vast array of biologically acti...

Aim: This study reports the designing of BChE inhibitors through machine learning (ML), followed by in silico and in vitro evaluations. Methodology: ML technique was used to predict the virtual hit, and its derivatives were synthesized and characterized. The compounds were evaluated by using various in vitro tests and in silico methods. Results: Th...

Structure-based drug design (SBDD) is an important in silico technique, used for the identification of enzyme inhibitors. Acetylcholinesterase (AChE), obtained from Electrophorus electricus (ee), is widely used for the screening of AChE inhibitors. It shares structural homology with the AChE of human and other organisms. Till date, the three-dimens...

Alzheimer's disease (AD), an extremely common neurodegenerative disorder of the older generation, is one of the leading causes of death globally. Besides the conventional hallmarks i.e. Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), neuroinflammation also serves as a major contributing factor in the pathogenesis of AD. There is mounting...

The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a transmembrane aspartyl-protease, that cleaves amyloid precursor protein (APP) at the β-site. The sequential proteolytic cleavage of APP, first by β-secretase and then by γ-secretase complex, leads to the production and release of amyloid-β peptide, a pathological hallmark of Alz...

The abundance, low cost, high density of functional groups and ease of purification of carbohydrates are among the most important features that make them a prime candidate for designing therapeutics. Several carbohydrate-based molecules, of both natural and synthetic origin, are known for their wide range of therapeutic activities. The incorporatio...

The outbreak of existing public health distress is threatening the entire world with emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel coronavirus disease 2019 (COVID-19) is mild in most people. However, in some elderly people with co-morbid conditions, it may progress to pneumonia, acute respirat...

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In our previous study, we screened the anti-cancer properties of 10 benzothiazole derivatives in cervical cancer cell lines. In the present study, we aimed to delineate the mechanism of the apoptotic pathway (whether intrinsic or extrinsic) following the treatment of N-(4-(benzo[d]thiazol-2-yl)phenyl)-5-chloro-2-methoxybenzamide (named as A-07) on...

Nicotinic receptors are ligand-gated ion channels, involved in the generation of action potential in post synaptic membrane and motor endplate. The α7 Nicotinic Acetylcholine Receptor (nAChR) is a class of nicotinic receptor involved in cognition. It is distributed in hippocampus, thalamus, sensory and information processing regions of the brain. T...

Crystallization of semi-crystalline polyaniline has been attempted by altering conditions such as nature of dopant acid and nature of oxidant by a one-pot chemical polymerization method. The samples were characterized by an array of analytical techniques. Highly ordered arrangement with sharp peaks was present in the X-ray powder diffraction patter...

Cancer, characterized by uncontrolled malignant neoplasm, is a leading cause of death in both advanced and emerging countries. Although, ample drugs are accessible in the market to intervene with tumor progression, none are totally effective and safe. Natural anthraquinone (AQ) equivalents such as emodin, aloe-emodin, alchemix and many synthetic an...

Enzyme aromatase uses several androgen substrates for the biosynthesis of estrogen, i.e. conversion of androstenedione to estrone and testosterone to biologically potent estradiol. Aromatase inhibitors (AIs) such as anastrozole, letrozole and exemestane have been established in standard endocrine therapy of breast cancer, by interfering with the es...

In this study, we prepared carbon dots (CDs) from wheat bran via hydrothermal treatment at 180°C for 3 h. The prepared CDs showed blue‐green fluorescence under UV light. The fluorescence emission study of the CDs revealed that they showed maximum fluorescence emission at 500 nm. The prepared CDs showed a high quantum yield of 33.23%. Solvent‐depend...

In the present study, we have synthesized a series of fifteen nipecotic acid 1,3,4-oxadiazole based hybrids with significant (60-78%) yields. All the compounds were characterized by using different spectroanalytical techniques such as FT-IR, ¹H-NMR, ¹³C-NMR, and elemental analysis. This design strategy was validated by using in vivo anti-epileptic...

Three-dimensional (3D) printing technology is an emerging and flourishing technique which has a tremendous potential to bring a paradigm shift in the pharmaceutical sector. Basically, 3D printing is a fabrication technique in which automatically layer-by-layer materials are being deposited to create various design of choice. The primary objective o...

Herein, a facile, green and eco‐friendly approach has been applied for the synthesis of fluorescent green‐blue carbon dots (GB‐CDs) through the one‐pot hydrothermal treatment of Artocarpus lakoocha seeds for the first time and entirely characterized via a variety of instrumental techniques like fluorescent spectroscopy, Transmission Electron Micros...

Leapfrogging appears at several levels and hence may be one of the fundamental processes generating urban fractality. Simulations have been performed on random pockets (slums) with different areas and lifetime of the Delhi city. The images were procured and processed using GIS package SAS planet and ImageJ and the fractal dimension was calculated b...

Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disease characterised by the appearance of amyloid β plaques and neurofibrillary tangles in the brain. The loss of cholinergic neurons is considered to be one of the contributing factors for cognitive and memory deficits in the disease. Donepezil, the most successful and pre...

Rani Lakshmi Bai Central Agricultural University, Jhansi conducted 40 front line demonstrations on mustard crop under the varieties - DRMR IJ-31, NRCHB -101, RH-749, NRCDR-2 and RH-406 during 2016–17. The critical reasons were identified in existing production technology through surveys and meetings with farmers. Sowing time, use of higher seed rat...

Recent clinical reports have highlighted the increasing occurrence of drug resistance of known therapeutics. Particularly, antibiotic resistant microorganisms and multidrug resistance have posed a serious threat to health of the people. Since ages, metals and metal complexes have played key role in the development of contemporary chemotherapy. Many...