Exploration of Structure-Activity Relationship Using Integrated Structure and Ligand Based Approach: Hydroxamic Acid-Based HDAC Inhibitors and Cytotoxic Agents.

The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for histone deacetylase (HDAC) inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anticancer activity. We have selected a dataset from earlier research findings. The target and ligand molecules were procured from recognized databases and incorporated into pivotal findings such as molecular docking (XP glide), e-pharmacophore study and 3D QSAR model designing study (phase).

Multi-targeted HDAC Inhibitors as Anticancer Agents: Current Status and Future Prospective.

Multi-targeted agents can interact with multiple targets sequentially, resulting in synergistic and more effective therapies for several complicated disorders, including cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are low molecular weight small compounds that increase the acetylation of histone and nonhistone proteins, altering gene expression and thereby impacting angiogenesis, metastasis, and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular pathways thus producing adverse issues, causing therapeutic resistance, and they have poor pharmacokinetic properties.

Combination Therapy for the Treatment of Alzheimer's Disease: Recent Progress and Future Prospects.

Background: The management of Alzheimer's disease is challenging due to its complexity. However, the currently approved and marketed treatments for this neurodegenerative disorder revolves around cholinesterase inhibitors, glutamate regulators, or the combination of these agents. Despite the prompt assurance of many new drugs, several agents were unsuccessful, especially in phase II or III trials, not meeting efficacy endpoints.

Corticosteroids for treatment of COVID-19: effect, evidence, expectation and extent.

Background: The World Health Organization (WHO) announced the COVID-19 occurrence as a global pandemic in March 2020. The treatment of SARS-CoV-2 patients is based on the experience gained from SARS-CoV and MERS-CoV infection during 2003. There is no clinically accepted therapeutic drug(s) accessible yet for the treatment of COVID-19.

Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention.

Angiotensin-converting enzyme (ACE) and its homologue, ACE2, are commonly allied with hypertension, renin-angiotensin-aldosterone system pathway, and other cardiovascular system disorders. The recent pandemic of COVID-19 has attracted the attention of numerous researchers on ACE2 receptors, where the causative viral particle, SARS-CoV-2, is established to exploit these receptors for permitting their entry into the human cells. Therefore, studies on the molecular origin and pathophysiology of the cell response in correlation to the role of ACE2 receptors to these viruses are bringing novel theories.

Synthetic and Semi-synthetic Drugs as a Promising Therapeutic Option for the Treatment of COVID-19.

The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from Wuhan, China, and has spread all around the world, affecting 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists.

The combination of histone deacetylase inhibitors and radiotherapy: a promising novel approach for cancer treatment.

HDAC inhibitors (HDACi) play an essential role in various cellular processes, such as differentiation and transcriptional regulation of key genes and cytostatic factors, cell cycle arrest and apoptosis that facilitates the targeting of epigenome of eukaryotic cells. In the majority of cancers, only a handful of patients receive optimal benefit from chemotherapeutics. Additionally, there is emerging interest in the use of HDACi to modulate the effects of ionizing radiations.

Highly selective fluorescence 'turn off' sensing of picric acid and efficient cell labelling by water-soluble luminescent anthracene-bridged poly(N-vinyl pyrrolidone).

A novel, water-soluble, luminescent anthracene-bridged AA-type bi-arm poly(N-vinylpyrrolidone) (ATC-PNVP) was synthesized using a click reaction between alkyne-terminated PNVP and 9,10-bis(azidomethyl)anthracene. The resultant anthracene-bridged PNVP (ATC-PNVP) was characterized using 1H NMR, FTIR, UV-Vis, and fluorescence spectroscopic methods and GPC analysis. ATC-PNVP showed effective fluorescence properties in an aqueous medium.

Identification of Hydroxamic Acid Based Selective HDAC1 Inhibitors: Computer Aided Drug Design Studies.

Background: Overexpression of Histone deacetylase 1 (HDAC1) is responsible for carcinogenesis by promoting epigenetic silence of tumour suppressor genes. Thus, HDAC1 inhibitors have emerged as the potential therapeutic leads against multiple human cancers, as they can block the activity of particular HDACs, renovate the expression of several tumour suppressor genes and bring about cell differentiation, cell cycle arrest and apoptosis.

Methods: The present research work comprises atom-based 3D-QSAR, docking, molecular dynamic simulations and DFT (density functional theory) studies on a diverse series of hydroxamic acid derivatives as selective HDAC1 inhibitors.

The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies.

Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations.

Infant and Young Child Feeding Practices in Infants Receiving Skin to Skin Care at Birth: Follow-up of Randomized Cohort.

Introduction: Skin to Skin Care (SSC) in neonatal period influences immediate breastfeeding outcomes in early childhood, especially the duration of exclusive breastfeeding.

Aim: We investigated influence of 17 hours of SSC given from day one of life on Infant and Young Child Feeding (IYCF) practices through one year of life.

Materials And Methods: Follow-up of a Superiority Randomized Control Trial (RCT) (CTRI/2013/06/003790) conducted in a teaching hospital located in central Gujarat.

Histone Deacetylase Inhibitors for the Treatment of Colorectal Cancer: Recent Progress and Future Prospects.

Background: Colorectal cancer is a devastating disease with a dismal prognosis which is heavily hampered by delayed diagnosis. Surgical resection, radiation therapy and chemotherapy are the curative options. Due to few therapeutic treatments available i.

Study of the Fluorescence Based Applications of Pyrene-Tagged Poly(-vinyl-2-pyrrolidone).

In this study we have explored the fluorescence based applications of luminescent pyrene-tagged PNVP (PyPNVP) reported in our previous work (Int. J. Polym.

Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.

Background: Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells.

Objective: To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies.

Method: The pharmacophore hypotheses were developed using e-pharmacophore script and phase module.

Drug Design Strategies for the Discovery of Novel Anticonvulsants Concerned with Four Site Binding Pharmacophoric Model Studies.

Anticonvulsant refers to a group of pharmaceuticals used in the treatment of epileptic seizures. The use of current antiepileptic drugs has been questioned due to the non-selectivity of the drugs and the undesirable side effects produced by them. This led to the search for antiepileptic compounds with more selectivity and lower toxicity.

Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives as novel anticancer agents.

A series of novel 2-amino-3,4,5 trimethoxyaroylindole derivatives was synthesized and evaluated against selected human cancer cell lines of breast (MCF-7) and colon (HT-29). Introduction of an amino group at the C-2 position on ring A of 3,4,5-trimethoxyaroylindole derivatives resulted in novel compounds, i.e.

Novel pyrimidine based semicarbazones: Confirmation of four binding site pharmacophoric model hypothesis for antiepileptic activity.

Background: Epilepsy is a neurological disorder, characterized by seizures accompanied by loss or disturbance of consciousness affecting various physical and mental functions. Current anticonvulsant drugs are effective in controlling seizures in about 70% of cases, but their use is often limited by side effects like ataxia, megaloblastic anemia, hepatic failure. In search for a novel anticovulsant drug with better efficacy and lower toxicity, a series of novel pyrimidine based semicarbazone were designed and evaluated for antiepileptic activity.

Panobinostat as Pan-deacetylase Inhibitor for the Treatment of Pancreatic Cancer: Recent Progress and Future Prospects.

The histone deacetylase (HDAC) inhibitors have been demonstrated as an emerging class of anticancer drugs. HDACs are involved in regulation of gene expression and in chromatin remodeling, thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac, LBH589) was developed by Novartis Pharmaceuticals and has been recently approved by the US Food and Drug Administraion (FDA) as a drug to treat multiple myeloma.

Practical synthesis of [n]cycloparaphenylenes (n = 5, 7-12) by H2SnCl4-mediated aromatization of 1,4-dihydroxycyclo-2,5-diene precursors.

Cyclic precursors of cycloparaphenylenes (CPPs) containing 1,4-dihydroxy-2,5-cyclohexadien-1,4-diyl units are prepared by modifying a synthetic method developed by Jasti and co-workers for the synthesis of corresponding 1,4-dimethoxy derivatives. Reductive aromatization of the diyl moieties by SnCl2/2 HCl takes place under mild conditions and affords the CPPs in good yields, incorporating 5 or 7-12 phenylene units. Highly strained [5]CPP is synthesized in greater than 0.

Tracheal Agenesis with Tracheo-oesophageal Fistula.

Tracheal Agenesis (TA) presents with respiratory distress at birth. Diagnosis requires recognition of clinical signs in newborns like failure of endotracheal intubation, respiratory distress with absent air entry over both side of chest and inaudible cry. We describe a TA Floyd Type I with a Tracheo-Oesophageal Fistula (TOF) without other congenital malformations.

Synthesis and characterization of [5]cycloparaphenylene.

The synthesis of highly strained [5]cycloparaphenylene ([5]CPP), a structural unit of the periphery of C60 and the shortest possible structural constituent of the sidewall of a (5,5) carbon nanotube, was achieved in nine steps in 17% overall yield. The synthesis relied on metal-mediated ring closure of a triethylsilyl (TES)-protected masked precursor 1c followed by removal of the TES groups and subsequent reductive aromatization. UV-vis and electrochemical studies revealed that the HOMO-LUMO gap of [5]CPP is narrow and is comparable to that of C60, as predicted by theoretical calculations.

Synthesis and study of the properties of stereocontrolled poly(N-isopropylacrylamide) gel and its linear homopolymer prepared in the presence of a Y(OTf)3 Lewis acid: effect of the composition of methanol-water mixtures as synthesis media.

Poly(N-isopropylacrylamide) (PNIPAM) hydrogels and the corresponding linear homopolymers were synthesized in different methanol-water mixtures (x(m) = 0, 0.13, 0.21, 0.

Synthesis and characterization of stereocontrolled poly(N-isopropylacrylamide) hydrogel prepared in the presence of Y(OTf)3 Lewis acid.

Macroporous poly(N-isopropylacrylamide) (PNIPAM) hydrogels have been prepared in methanol-water (1:1, v/v) mixture in the presence of 0, 0.05, 0.1, 0.