Medicinal Chemistry Strategies Towards SO2 Donors as Research Tools and Potential Therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Eman M. El-labbad ◽  
Xingyue Ji ◽  
Khaled A.M. Abouzid ◽  
Binghe Wang
Keyword(s):  
Small Molecule ◽  
Medicinal Chemistry ◽  
Therapeutic Agent ◽  
Pharmacological Effects ◽  
Signaling Molecule ◽  
The Past ◽  
Potential Therapeutic Agent ◽  
Release Mechanisms ◽  
Potential Therapeutics ◽  
Research Tools

SO2 is emerging as a possible endogenous signaling molecule in mammals. In addition, SO2 has also shown pharmacological effects, presenting SO2 as a promising potential therapeutic agent. The past decade has witnessed steady advances in the development of small molecule-based SO2 prodrugs/donors with varied release mechanisms. Herein, we summarize various strategies employed for SO2 prodrug design. The remaining challenges and issues will also be discussed.

scholarly journals STAT3 inhibition suppresses hepatic stellate cell fibrogenesis: HJC0123, a potential therapeutic agent for liver fibrosis

RSC Advances ◽  
2016 ◽  
Vol 6 (102) ◽  
pp. 100652-100663 ◽  
Author(s):  
Omar Nunez Lopez ◽  
Fredrick J. Bohanon ◽  
Xiaofu Wang ◽  
Na Ye ◽  
Tiziana Corsello ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Small Molecule ◽  
Hepatic Stellate Cell ◽  
Potential Role ◽  
Therapeutic Agent ◽  
Stellate Cell ◽  
The Novel ◽  
Potential Therapeutic Agent ◽  
Human Hscs ◽  
Stat3 Inhibition

The novel small molecule HJC0123 will inhibit STAT3 activation in human HSCs resulting in decreased fibrogenesis, unveiling a potential role for its use as a therapeutic agent for the treatment of liver fibrosis.

scholarly journals Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (16) ◽  
pp. 26169-26184 ◽  
Author(s):  
Helga Weber ◽  
José R. Valbuena ◽  
Mustafa A. Barbhuiya ◽  
Stefan Stein ◽  
Hana Kunkel ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Small Molecule ◽  
Therapeutic Agent ◽  
Hsp90 Inhibitor ◽  
Small Molecule Inhibitor ◽  
Inhibitor Screening ◽  
Potential Therapeutic Agent ◽  
Molecule Inhibitor

Boron in Medicinal and Organic Chemistry

2021 ◽  
Vol 25 ◽  
Author(s):  
João Lucas Bruno Prates ◽  
Aline Renata Pavan ◽  
Jean Leandro dos Santos
Keyword(s):  
Organic Synthesis ◽  
Boronic Acid ◽  
Medicinal Chemistry ◽  
Therapeutic Agent ◽  
Chemical Properties ◽  
Cross Coupling ◽  
Review Article ◽  
Coupling Reactions ◽  
The Past ◽  
Cross Coupling Reactions

: Nowadays, boron-containing compounds have gained researchers’ attention because of the wide versatility and applicability of this element in both organic and medicinal chemistry. Since its discovery, its use in medicinal chemistry was neglected due to its possible toxic effects. However, in the past years, boron-containing compounds did not show such effects, and some drugs have already been approved by the Food and Drug Administration to treat diseases, including cancer, infections, and inflammation. Several boron-containing compounds are used in organic and medicinal chemistry, either as a reagent or therapeutic agent. The chemical properties of this element make its use possible in organic synthesis as a reducing agent and catalyst, mainly in cross-coupling reactions. Among boron-containing compounds, boranes, azaborines, benzoxaborole, boronic acid, and boron derivatives are most commonly described. This review article discusses the main properties of boron-containing compounds, their preparation by organic synthesis, as well as their applications in organic synthesis and medicinal chemistry fields, developing new perspectives for further investigations.

scholarly journals Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 114
Author(s):  
Joseph A. Piscatelli ◽  
Jisun Ban ◽  
Andrew T. Lucas ◽  
William C. Zamboni
Keyword(s):  
Drug Delivery ◽  
Small Molecule ◽  
Drug Delivery Systems ◽  
Systemic Exposure ◽  
Clinical Development ◽  
Pharmacological Effects ◽  
Safety And Efficacy ◽  
The Past ◽  
Tumor Delivery ◽  
Systemic Disposition

Major developments in nanomedicines, such as nanoparticles (NPs), nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past four decades. Although nanocarrier agents provide numerous advantages (e.g., greater solubility and duration of systemic exposure) compared to their small-molecule counterparts, there is considerable inter-patient variability seen in the systemic disposition, tumor delivery and overall pharmacological effects (i.e., anti-tumor efficacy and unwanted toxicity) of NP agents. This review aims to provide a summary of fundamental factors that affect the disposition of NPs in the treatment of cancer and why they should be evaluated during preclinical and clinical development. Furthermore, this chapter will highlight some of the translational challenges associated with elements of NPs and how these issues can only be addressed by detailed and novel pharmacology studies.

Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

2018 ◽  
Vol 25 (5) ◽  
pp. 636-658 ◽  
Author(s):  
Jan Pokorny ◽  
Lucie Borkova ◽  
Milan Urban
Keyword(s):  
Biological Activities ◽  
Synthetic Approach ◽  
Clinical Use ◽  
New Approach ◽  
Click Reactions ◽  
Drug Candidates ◽  
The Past ◽  
Low Toxicity ◽  
New Compounds ◽  
Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

Microbial Genetic Screens for Monitoring Protein Misfolding Associated with Neurodegeneration: Tools for Identifying Disease-Relevant Genes and for Screening Synthetic and Natural Compound Libraries for the Discovery of Potential Therapeutics

2018 ◽  
Vol 24 (19) ◽  
pp. 2055-2075 ◽  
Author(s):  
Kalliopi Kostelidou ◽  
Ilias Matis ◽  
Georgios Skretas
Keyword(s):  
Protein Misfolding ◽  
Socioeconomic Impact ◽  
Genetic Screens ◽  
Subsequent Formation ◽  
The Past ◽  
Compound Libraries ◽  
Selection Systems ◽  
Cellular Factors ◽  
Effective Drugs ◽  
Potential Therapeutics

Neurodegenerative Diseases (ND) are a major threat to the aging population and the lack of a single preventive or disease-modifying agent only serves to increase their impact. In the past few years, protein misfolding and the subsequent formation of neurotoxic oligomeric/aggregated protein species have emerged as a unifying theme underlying the pathology of these complex diseases. Recently developed microbial genetic screens and selection systems for monitoring ND-associated protein misfolding have allowed the establishment of highthroughput assays for the identification of cellular factors and processes that are important mediators of NDassociated proteotoxicities. In addition, such systems have facilitated the discovery of synthetic and natural compounds with the ability to rescue the misfolding and the associated pathogenic effects of aggregation-prone proteins associated with NDs. This review outlines such available systems in bacteria and yeast, whose usage will likely accelerate the pre-clinical discovery process for effective drugs against a variety of NDs with high socioeconomic impact.

Identification of 2-Fluoropalmitic Acid as a Potential Therapeutic Agent Against Glioblastoma

2020 ◽  
Vol 26 (36) ◽  
pp. 4675-4684 ◽  
Author(s):  
Shabierjiang Jiapaer ◽  
Takuya Furuta ◽  
Yu Dong ◽  
Tomohiro Kitabayashi ◽  
Hemragul Sabit ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Screening ◽  
Therapeutic Agent ◽  
Gelatin Zymography ◽  
Therapeutic Agents ◽  
Drug Candidate ◽  
Potential Therapeutic Agent ◽  
Sphere Formation ◽  
Improve Patient

Background: Glioblastomas (GBMs) are aggressive malignant brain tumors. Although chemotherapy with temozolomide (TMZ) can extend patient survival, most patients eventually demonstrate resistance. Therefore, novel therapeutic agents that overcome TMZ chemoresistance are required to improve patient outcomes. Purpose: Drug screening is an efficient method to find new therapeutic agents from existing drugs. In this study, we explored a novel anti-glioma agent by drug screening and analyzed its function with respect to GBM treatment for future clinical applications. Methods: Drug libraries containing 1,301 diverse chemical compounds were screened against two glioma stem cell (GSC) lines for drug candidate selection. The effect of selected agents on GSCs and glioma was estimated through viability, proliferation, sphere formation, and invasion assays. Combination therapy was performed to assess its ability to enhance TMZ cytotoxicity against GBM. To clarify the mechanism of action, we performed methylation-specific polymerase chain reaction, gelatin zymography, and western blot analysis. Results: The acyl-CoA synthetase inhibitor 2-fluoropalmitic acid (2-FPA) was selected as a candidate anti-glioma agent. 2-FPA suppressed the viability and stem-like phenotype of GSCs. It also inhibited proliferation and invasion of glioma cell lines. Combination therapy of 2-FPA with TMZ synergistically enhanced the efficacy of TMZ. 2-FPA suppressed the expression of phosphor-ERK, CD133, and SOX-2; reduced MMP-2 activity; and increased methylation of the MGMT promoter. Conclusion: 2-FPA was identified as a potential therapeutic agent against GBM. To extend these findings, physiological studies are required to examine the efficacy of 2-FPA against GBM in vivo.

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