scholarly journals Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yasaman Malekizadeh ◽  
Gareth Williams ◽  
Mark Kelson ◽  
David Whitfield ◽  
Jonathan Mill ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Side Effects ◽  
Atypical Antipsychotic ◽  
Mechanism Of Action ◽  
In Silico ◽  
In Silico Screening ◽  
Whole Transcriptome ◽  
Antipsychotic Side Effects

Recognizing and Responding to Atypical Antipsychotic Side Effects

2004 ◽  
Vol 5 (4) ◽  
pp. H7-H10 ◽  
Author(s):  
Jeanne M. Jackson-Siegal ◽  
Lon S. Schneider ◽  
Andrius Baskys ◽  
Daniel W. Haupt
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotic ◽  
Antipsychotic Side Effects

Role of α1 adrenergic antagonism in the mechanism of action of iloperidone: reducing extrapyramidal symptoms

CNS Spectrums ◽  
2013 ◽  
Vol 18 (6) ◽  
pp. 285-288 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotic ◽  
Mechanism Of Action ◽  
Adrenergic Receptors ◽  
Extrapyramidal Side Effects ◽  
Binding Profile ◽  
High Affinity ◽  
Low Incidence ◽  
Serotonin 2A

ISSUE:The low incidence of extrapyramidal side effects associated with the atypical antipsychotic iloperidone may be linked to its unique binding profile of high affinity antagonism of both α1 adrenergic receptors and serotonin 2A receptors.

scholarly journals In silico screening of drug-like molecules for the treatment of cardiovascular diseases on the basis of five-membered privileged heterocycles

2019 ◽  
pp. 61-72 ◽  
Author(s):  
І. V. Drapak
Keyword(s):  
Cardiovascular Diseases ◽  
Acute Toxicity ◽  
Mechanism Of Action ◽  
In Silico ◽  
Rational Design ◽  
In Silico Screening ◽  
Drug Mechanism ◽  
Synthetic Drug ◽  
Toxicity Level ◽  
Derivatives Of

Among various heterocyclic systems, the derivatives of five-membered heterocycles are of special interest. Most of the above mentioned heterocycles are treatred as so-called privileged structures in modern medicinal chemistry. In silico screening among five-membered heterocycles of molecules for the treatment of cardiovascular diseases is actual. The aim of the work was the search for synthetic drug-like molecules based on functionalized five-membered heterocycles and related heterocyclic systems as an element of the theoretical platform for rational design of compounds acting on the cardiovascular system, and prediction of their possible mechanism of action. The objects of the study were derivatives of uncondensed and condensed five-membered heterocycles. In the work, in silico approaches were applied using the programs: Hyper-Chem, PASS, AutoDock, PROTOX. Based on the previous studies, focused sub-libraries of small synthetic drug-like molecules based on functionalized five-membered heterocycles and related heterocyclic systems have been selected. The compounds were divided on 12 groups. The optimization of the compound structures, the drug-like parameters calculation were carried out. The activity prediction, the acute toxicity level and docking studies to probable bio-targets which are related with cardiovascular drug mechanism of action have been carried out. It was shown that thiazole and thiadiazole based compounds possessed the highest calculated affinity levels to selected bio-targets. This is consistent with PASS-based prediction data. Diverse functionalized derivatives of five-membered heterocycles (thiazole, thiazolidine, thiadiazole, pyrazole, thiophene, triazole)  and related fused heterocycles have been grouped in focused sub-libraries of compounds. it has been established that thiazole and thiadiazole based compounds are promising objects for directed synthesis and further modification as potential cardiovascular agents based on the prediction of biological activity, the calculation of affinity to potent bio-targets, and the prediction of the drug-like features and acute toxicity level. The prognostic values of the parameters of the above mentioned groups of compounds may be used as the element of theoretical platform for the search and de novo design of potential drugs for the treatment of cardiovascular diseases.

Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

2019 ◽  
Author(s):  
Veeren Chauhan ◽  
Mohamed M Elsutohy ◽  
C Patrick McClure ◽  
Will Irving ◽  
Neil Roddis ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Point Of Care ◽  
Lateral Flow ◽  
Nucleic Acid Sequence ◽  
In Silico Screening ◽  
Lateral Flow Assays ◽  
Life Threatening ◽  
Software And Hardware ◽  
Nucleic Acid Sequences

<p>Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10<sup>-7</sup> M, ≥1.4×10<sup>-14</sup> g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.</p>

Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Bichismita Sahu ◽  
Santosh Kumar Behera ◽  
Rudradip Das ◽  
Tanay Dalvi ◽  
Arnab Chowdhury ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Peptide Nucleic Acid ◽  
Large Set ◽  
Nonstructural Proteins ◽  
In Silico Screening ◽  
Replication Process ◽  
Enveloped Virus ◽  
Treatment Regimens ◽  
Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs

2019 ◽  
Vol 19 (9) ◽  
pp. 1080-1102 ◽  
Author(s):  
Ghansham S. More ◽  
Asha B. Thomas ◽  
Sohan S. Chitlange ◽  
Rabindra K. Nanda ◽  
Rahul L. Gajbhiye
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Cross Linking ◽  
Nitrogen Mustards ◽  
Information Leaflets ◽  
Anti Cancer ◽  
Approved Drugs

Background & Objective: :Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents.Methods::An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated.Results::This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market.Conclusion: :Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.

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