The crystalline salt form of a selected candidate drug showed photo-, thermal- and humidity induced form transitions

In the case of solubility limited absorption, creating supersaturation in the GI fluid is very critical as supersaturation may provide great improvement of oral absorption. The techniques to create the so-called supersaturation in the GI fluid include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles. Ciprofloxacin was chosen because it is practically insoluble in water; hence its salt form is used commercially, which is soluble in water. The objective of the present investigation was to enhance the solubility of Ciprofloxacin by formulating it into microemulsion system. For this purpose, initially, surfactant and cosurfactant were selected based on their HLB value, followed by pseudo-ternary phase diagrams to identify the microemulsion existing zone. Different formulations were developed and evaluated for pH, conductivity, in vitro release and stability. Solubility study was performed for optimized formulation. The pH of the designed formulations varied from 6.02-7.04. This was ideal and near blood pH 7.4. Conductivity data indicated that the microemulsion was of the o/w type. In vitro release of optimized formulation(FM3) was 95.2% as compared to pure drug 46.61% after 90 min and marketed product(salt form) 93.9%. Hence, by formulating into microemulsion, the solubility of ciprofloxacin is significantly enhanced.

Download Full-text

K+KCO8-: an antipodal crystalline salt of alkalide KC222+K-

Chemical Physics Letters ◽

10.1016/j.cplett.2021.138508 ◽

2021 ◽

pp. 138508

Author(s):

Xiao-Yong Yang

Keyword(s):

Crystalline Salt

Download Full-text

Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

Scientific Reports ◽

10.1038/s41598-021-84044-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sinead M. O’Donovan ◽

Ali Imami ◽

Hunter Eby ◽

Nicholas D. Henkel ◽

Justin Fortune Creeden ◽

...

Keyword(s):

Infected Cell ◽

Mek Inhibitor ◽

Therapeutic Agents ◽

The Novel ◽

Integrated Network ◽

Candidate Drug ◽

Novel Targets ◽

Additional Support ◽

Bioinformatics Workflow

AbstractThe COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.

Download Full-text

A Multi-Pronged Computational Pipeline for Prioritizing Drug Target Strategies for Latent Tuberculosis

Frontiers in Chemistry ◽

10.3389/fchem.2020.593497 ◽

2020 ◽

Vol 8 ◽

Author(s):

Ushashi Banerjee ◽

Santhosh Sankar ◽

Amit Singh ◽

Nagasuma Chandra

Keyword(s):

Drug Targets ◽

Metabolic Flux ◽

Latent Tuberculosis ◽

Interaction Network ◽

New Drugs ◽

Prolonged Treatment ◽

Flux Analysis ◽

Protein Protein Interaction ◽

Candidate Drug ◽

Global Population

Tuberculosis is one of the deadliest infectious diseases worldwide and the prevalence of latent tuberculosis acts as a huge roadblock in the global effort to eradicate tuberculosis. Most of the currently available anti-tubercular drugs act against the actively replicating form of Mycobacterium tuberculosis (Mtb), and are not effective against the non-replicating dormant form present in latent tuberculosis. With about 30% of the global population harboring latent tuberculosis and the requirement for prolonged treatment duration with the available drugs in such cases, the rate of adherence and successful completion of therapy is low. This necessitates the discovery of new drugs effective against latent tuberculosis. In this work, we have employed a combination of bioinformatics and chemoinformatics approaches to identify potential targets and lead candidates against latent tuberculosis. Our pipeline adopts transcriptome-integrated metabolic flux analysis combined with an analysis of a transcriptome-integrated protein-protein interaction network to identify perturbations in dormant Mtb which leads to a shortlist of 6 potential drug targets. We perform a further selection of the candidate targets and identify potential leads for 3 targets using a range of bioinformatics methods including structural modeling, binding site association and ligand fingerprint similarities. Put together, we identify potential new strategies for targeting latent tuberculosis, new candidate drug targets as well as important lead clues for drug design.

Download Full-text

Fucoxanthin and Colorectal Cancer Prevention

Cancers ◽

10.3390/cancers13102379 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2379

Author(s):

Masaru Terasaki ◽

Atsuhito Kubota ◽

Hiroyuki Kojima ◽

Hayato Maeda ◽

Kazuo Miyashita ◽

...

Keyword(s):

Colorectal Cancer ◽

Brown Algae ◽

Lifestyle Modification ◽

Signal Pathways ◽

Potential Candidate ◽

Anticancer Effects ◽

Cancer Models ◽

Candidate Drug ◽

Colorectal Cancer Prevention ◽

Dietary Carotenoid

Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

Download Full-text