Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

Download Full-text

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180220125406 ◽

2018 ◽

Vol 21 (3) ◽

pp. 215-221

Author(s):

Haroon Khan ◽

Muhammad Zafar ◽

Helena Den-Haan ◽

Horacio Perez-Sanchez ◽

Mohammad Amjad Kamal

Keyword(s):

In Silico ◽

Docking Studies ◽

In Vivo Studies ◽

In Vitro Assays ◽

Chronic Obstructive ◽

Lipoxygenase Inhibitors ◽

Lipoxygenase Inhibition ◽

In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Download Full-text

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Thiazole-Dihyrofuran Derivatives as Aromatase Inhibitors

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.105123 ◽

2021 ◽

pp. 105123

Author(s):

Derya Osmaniye ◽

Şennur Görgülü ◽

Begum Nurpelin Saglik ◽

Serkan Levent ◽

Yusuf Ozkay ◽

...

Keyword(s):

Aromatase Inhibitors ◽

In Silico ◽

Design Synthesis ◽

In Silico Studies

Download Full-text

Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators

Journal of Enzyme Inhibition and Medicinal Chemistry ◽

10.1080/14756366.2021.1916009 ◽

2021 ◽

Vol 36 (1) ◽

pp. 1370-1377

Author(s):

Daniel A. S. Kitagawa ◽

Rafael B. Rodrigues ◽

Thiago N. Silva ◽

Wellington V. dos Santos ◽

Vinicius C. V. da Rocha ◽

...

Keyword(s):

In Silico ◽

Design Synthesis ◽

In Vitro Evaluation ◽

In Silico Studies ◽

Acetylcholinesterase Reactivators

Download Full-text

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Triazoles as Anticancer Agents for Breast Cancer

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131198 ◽

2021 ◽

pp. 131198

Author(s):

Derya Osmaniye ◽

Begum Nurpelin Saglik ◽

Serkan Levent ◽

Sinem Ilgın ◽

Yusuf Ozkay ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

In Silico ◽

Design Synthesis ◽

In Silico Studies

Download Full-text

Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

Natural Product Communications ◽

10.1177/1934578x211016610 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110166

Author(s):

Xin Yi Lim ◽

Janice Sue Wen Chan ◽

Terence Yew Chin Tan ◽

Bee Ping Teh ◽

Mohd Ridzuan Mohd Abd Razak ◽

...

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Rna Binding ◽

Symptomatic Relief ◽

Andrographis Paniculata ◽

Spike Protein ◽

Rapid Review ◽

In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

Download Full-text