Recent Development of DNA Gyrase Inhibitors: An Update.

Antibiotic or antimicrobial resistance is an urgent global public health threat that occurs when bacterial or fungal infections do not respond to the drug regimen designed to treat these infections. As a result, these microbes are not evaded and continue to grow. Antibiotic resistance against natural and already-known antibiotics like Ciprofloxacin and Novobiocin can be overcome by developing an agent that can act in different ways.

1,3,4-Thiadiazole: A Versatile Pharmacophore of Medicinal Significance.

The 1,3,4-thiadiazole nucleus has attracted the attention of medicinal chemists during the last decades due to its multiple pharmacological activities, such as antiviral, anticancer, antibacterial, and anticonvulsant activity. This scaffold's structural alteration could aid in developing novel therapeutically effective drugs. Incorporating this adaptable pharmacophore into a well-established medicinally active molecule results in hybrid molecules with diverse pharmacological effects.

Systematic Design, Synthesis, and Biological Studies of Some Novel 1,4-Benzoquinone Derivatives for the Prospective Management of Cognitive Decline.

Cholinesterases are significant biological targets for the regulation of cholinergic neurotransmission, and their inhibitors are being exploited for the management of cognitive decline in various neurological conditions. The 1,4-benzoquinone scaffold possesses antioxidant potential along with AChE inhibition activity in various neurological disorders. To design novel and potent selective 1,4-benzoquinone analogues as cholinesterase inhibitors, a ligand-based drug design strategy was followed to develop a 3D quantitative structure-selectivity relationship (QSSR) model.

Design, synthesis and biological evaluation of triazole-oxadiazole conjugates for the management of cognitive dysfunction.

Acetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this, the present study demonstrates the design, synthesis and pharmacological evaluation of triazole-oxadiazole conjugates.

Investigation of Molecular Properties of Antiretroviral Agents to Enhance CNS Penetration Abilities for the Treatment of Cognitive Impairment in HIV-Associated Neurocognitive Disorder.

HIV-associated neurocognitive disorder (HAND) can be represented by neurological and neuropathological abnormalities with a consequence of motor and cognitive loss. It has become a critical unmet medical need for infected people, and the number continues to rise every year. Pathological investigations have revealed its occurrence due to the release of free radicals from the HIV infected microglia and macrophages.

p-Benzoquinone as a Privileged Scaffold of Pharmacological Significance: A Review.

Quinones are a huge class of compounds with affluent and captivating chemistry. p-Benzoquinone (p-BNZ) or 1,4-Benzoquinone is the key structural motif of numerous biologically active synthetic and natural compounds. This draws interest in its biological exploration to assess prospective therapeutic implications.

Exploring the Chemistry and Therapeutic Potential of Triazoles: A Comprehensive Literature Review.

Triazole is a valuable platform in medicinal chemistry, possessing assorted pharmacological properties, which could play a major role in the common mechanisms associated with various disorders like cancer, infections, inflammation, convulsions, oxidative stress and neurodegeneration. Structural modification of this scaffold could be helpful in the generation of new therapeutically useful agents. Although research endeavors are moving towards the growth of synthetic analogs of triazole, there is still a lot of scope to achieve drug discovery break-through in this area.

Rho-kinase (ROCK) Inhibitors - A Neuroprotective Therapeutic Paradigm with a Focus on Ocular Utility.

Background: Glaucoma is a progressive optic neuropathy causing visual impairment and Retinal Ganglionic Cells (RGCs) death gradually posing a need for neuroprotective strategies to minimize the loss of RGCs and visual field. It is recognized as a multifactorial disease, Intraocular Pressure (IOP) being the foremost risk factor. ROCK inhibitors have been probed for various possible indications, such as myocardial ischemia, hypertension, kidney diseases.

Design, synthesis and pharmacological evaluation of some novel indanone derivatives as acetylcholinesterase inhibitors for the management of cognitive dysfunction.

The present study reports the effect of indanone derivatives on scopolamine induced deficit cholinergic neurotransmission serving as promising leads for the therapeutics of cognitive dysfunction. Eleven compounds 54-64 have been designed, synthesised and evaluated against behavioural alterations using step down passive avoidance protocol at a dose of 0.5 mg/kg with Donepezil (1) as the reference standard.

Design and synthesis of benzimidazole-based Rho kinase inhibitors for the treatment of glaucoma.

Rho kinase inhibitors (ROCK II) play a key role in glaucoma management attributed to their IOP lowering ability and neuroprotective effects. In the present study, a series of novel benzimidazole derivatives (9a-m) has been synthesized and evaluated for their IOP lowering, Rho kinase inhibitory and antioxidant properties. The synthesized compounds were found to be lipophilic and showed a significant IOP lowering effect both in the treated and the contralateral eye comparable to the reference standard fasudil.

N-(4-Hydroxyphenyl)-3,4,5-trimethoxybenzamide derivatives as potential memory enhancers: synthesis, biological evaluation and molecular simulation studies.

The present paper describes the synthesis, biological evaluation and molecular simulation studies of a series of N-(4-hydroxyphenyl)-3,4,5-trimethoxybenzamide derivatives with N,N-dialkylaminoethoxy/propoxy moiety as potential memory enhancers with acetylcholinesterase-inhibiting activity having IC in low micromolar range (4.0-16.5 μM).

Design and synthesis of some acridine-piperazine hybrids for the improvement of cognitive dysfunction.

A novel series of hybrid molecules (5a-5m) was designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against cognitive dysfunction. Heterocyclic moieties acridine and piperazine were conjugated with suitable linkers in a single scaffold, and the structures of the target compounds were confirmed by IR, H NMR, C NMR, and LC-MS analysis. The pharmacological activity of synthesized compounds was evaluated using behavioral models of amnesia viz.

Design, Synthesis and Molecular Docking Studies of New Potential Piperazine Derivatives as Cognition Enhancers.

Background: In 2016, the statistical reports stated that Alzheimer is not just memory loss but it kills and has become the 6th leading cause of death. The number of dementia patients is increasing rapidly and expected to rise to 131.5 million by 2050.

Coumarin derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies.

A series of novel hybrids has been synthesized by linking coumarin moiety through an appropriate spacer to various substituted heterocyclic amines and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of cognitive dysfunction caused by increased hydrolysis of acetylcholine and scopolamine induced oxidative stress. Anti-amnesic activity of the compounds was evaluated using Morris water maze model at a dose of 1mg/kg with reference to the standard, donepezil. Biochemical estimation of oxidative stress markers (lipid peroxidation, superoxide dismutase, and plasma nitrite) was carried out to assess the antioxidant potential of the synthesized molecules.

Ameliorative effects of amide derivatives of 1,3,4-thiadiazoles on scopolamine induced cognitive dysfunction.

The present study reports the effect of amide derivatives of 1,3,4-thiadizoles on scopolamine induced deficit cholinergic neurotransmission and oxidative stress serving as promising leads for the therapeutics of cognitive dysfunction. Fourteen compounds (2c-8d) have been synthesised and evaluated against behavioural alterations using step down passive avoidance protocol and morris water maze and at a dose of 0.5 mg/kg with reference to the standard, Rivastigmine.

Current pharmacotherapy and putative disease-modifying therapy for Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease of the central nervous system correlated with the progressive loss of cognition and memory. β-Amyloid plaques, neurofibrillary tangles and the deficiency in cholinergic neurotransmission constitute the major hallmarks of the AD. Two major hypotheses have been implicated in the pathogenesis of AD namely the cholinergic hypothesis which ascribed the clinical features of dementia to the deficit cholinergic neurotransmission and the amyloid cascade hypothesis which emphasized on the deposition of insoluble peptides formed due to the faulty cleavage of the amyloid precursor protein.

Design and synthesis of newer potential 4-(N-acetylamino)phenol derived piperazine derivatives as potential cognition enhancers.

A series of novel hybrids has been designed, synthesized and evaluated for cognition enhancing activities through the inhibition of acetylcholinesterase (AChE) and by passive avoidance mouse model. All the compounds showed excellent AChE inhibition activities and potentially reversed the scopolamine induced memory deficit. Enzyme kinetic and molecular docking studies have confirmed their dual binding affinity and mixed type inhibition.

The discovery and development of new potential antioxidant agents for the treatment of neurodegenerative diseases.

Introduction: Several neurodegenerative disorders (NDs) including Alzheimer's and Huntington's diseases have had associations with the oxidative process and free radical damage. Consequently, in past decades, several natural and synthetic antioxidants have been assessed as therapeutic agents but have shown limitations in bioavailability, metabolic susceptibility and permeability to the blood brain barrier. Given these issues, medicinal chemists are hard at work to modify/improve the chemical structures of these antioxidants, thereby improving their efficacy.

Rho Kinase Inhibitors and Novel Ocular Drug Delivery Systems- A Revolutionary Step Towards the Treatment of Glaucoma.

Background: Glaucoma is an ocular disorder characterized by optic nerve damage which ultimately causes a progressive and an irreversible loss of vision, often characterized by an elevated intraocular pressure. Lowering the intraocular pressure (IOP) is the mainstay for glaucoma treatment but the neuroprotective agents would represent a promising class as the next-generation therapy.

Evidence Synthesis: Protein kinases are involved considerably in signal transduction pathways confirmed by various mechanisms giving the evidence of Rho-kinase to be a versatile therapeutic target.

Acetylcholinesterase inhibitors from QSAR point of view: how close are we?

In view of the large libraries of acetylcholinesterase inhibitors (AChEIs) that are now being handled in organic synthesis, the identification of drug biological activity is advisable prior to synthesis and this can be achieved by employing predictive biological property methods. In this sense, Quantitative Structure-Activity Relationships (QSAR) or docking approaches have emerged as promising tools. The intention of this review is to summarize the present knowledge concerning computational predictions of AChEIs and AChE.

Molecular docking and receptor-specific 3D-QSAR studies of acetylcholinesterase inhibitors.

The reversible inhibition of acetylcholinesterase (AChE) has become a promising target for the treatment of Alzheimer's disease (AD) which is mainly associated with low in vivo levels of acetylcholine (ACh). The availability of AChE crystal structures with and without a ligand triggered the effort to find a structure-based design of acetylcholinesterase inhibitors (AChEIs) for AD. The major problem observed with the structure-based design was the feeble robustness of the scoring functions toward the correlation of docking scores with inhibitory potencies of known ligands.

Synthesis, molecular docking and antiamnesic activity of selected 2- naphthyloxy derivatives.

The present paper describes the design and synthesis of a series of some 2-naphthyloxy derivatives with their antiamnesic activity using mice as the animal model and piracetam as the reference drug. All the synthesized compounds were characterized by spectroscopic techniques and were screened for their efficacy as cognition enhancers by elevated plus maze test and acetylcholinestrase inhibitory assay. Molecular modeling and docking studies of the selected compounds into the crystal structure of acetylcholinestrase complexed with functional ligand succinylcholine using GRAMM software was performed in order to predict the affinity and orientation of the synthesized derivatives at the active site.

Synthesis and pharmacological evaluation of some quinoline derivatives as potential cognition enhancers.

The present paper describes the synthesis of a series of substituted 6-amino (1a-c) and 8-aminoquinoline derivatives (2b-c) and the evaluation of their ability to prevent the memory decline using a behavioural model, i.e. the elevated plus maze test.

N-[4-(2-Morpholino-eth-oxy)phen-yl]acetamide monohydrate.

In the title compound, C(14)H(20)N(2)O(3)·H(2)O, the geometry about the morpholine N atom implies sp(3) hybridization. In the crystal, symmetry-related mol-ecules are linked by inter-molecular N-H⋯O, O-H⋯O and O-H⋯N hydrogen bonds, forming infinite chains along the b axis. The chain structure is further stabilized by intra-molecular C-H⋯O inter-actions.